Skip to main content
NCBI home page
Protein Science : A Publication of the Protein Society logoLink to Protein Science : A Publication of the Protein Society
. 1995 Mar;4(3):337–360. doi: 10.1002/pro.5560040301

Structural basis of substrate specificity in the serine proteases.

J J Perona 1, C S Craik 1
PMCID: PMC2143081  PMID: 7795518

Abstract

Structure-based mutational analysis of serine protease specificity has produced a large database of information useful in addressing biological function and in establishing a basis for targeted design efforts. Critical issues examined include the function of water molecules in providing strength and specificity of binding, the extent to which binding subsites are interdependent, and the roles of polypeptide chain flexibility and distal structural elements in contributing to specificity profiles. The studies also provide a foundation for exploring why specificity modification can be either straightforward or complex, depending on the particular system.

Full Text

The Full Text of this article is available as a PDF (21.2 MB).

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Abrahmsén L., Tom J., Burnier J., Butcher K. A., Kossiakoff A., Wells J. A. Engineering subtilisin and its substrates for efficient ligation of peptide bonds in aqueous solution. Biochemistry. 1991 Apr 30;30(17):4151–4159. doi: 10.1021/bi00231a007. [DOI] [PubMed] [Google Scholar]
  2. Bash P. A., Singh U. C., Langridge R., Kollman P. A. Free energy calculations by computer simulation. Science. 1987 May 1;236(4801):564–568. doi: 10.1126/science.3576184. [DOI] [PubMed] [Google Scholar]
  3. Bauer C. A. Active centers of Streptomyces griseus protease 1, Streptomyces griseus protease 3, and alpha-chymotrypsin: enzyme-substrate interactions. Biochemistry. 1978 Jan 24;17(2):375–380. doi: 10.1021/bi00595a028. [DOI] [PubMed] [Google Scholar]
  4. Bauer C. A., Brayer G. D., Sielecki A. R., James M. N. Active site of alpha-lytic protease: enzyme-substrate interactions. Eur J Biochem. 1981 Nov;120(2):289–294. doi: 10.1111/j.1432-1033.1981.tb05702.x. [DOI] [PubMed] [Google Scholar]
  5. Bauer C. A., Thompson R. C., Blout E. R. The active centers of Streptomyces griseus protease 3 and alpha-chymotrypsin: enzyme-substrate interactions remote from the scissile bond. Biochemistry. 1976 Mar 23;15(6):1291–1295. doi: 10.1021/bi00651a019. [DOI] [PubMed] [Google Scholar]
  6. Bech L. M., Sørensen S. B., Breddam K. Mutational replacements in subtilisin 309. Val104 has a modulating effect on the P4 substrate preference. Eur J Biochem. 1992 Nov 1;209(3):869–874. doi: 10.1111/j.1432-1033.1992.tb17359.x. [DOI] [PubMed] [Google Scholar]
  7. Bech L. M., Sørensen S. B., Breddam K. Significance of hydrophobic S4-P4 interactions in subtilisin 309 from Bacillus lentus. Biochemistry. 1993 Mar 23;32(11):2845–2852. doi: 10.1021/bi00062a016. [DOI] [PubMed] [Google Scholar]
  8. Bender M. L., Killheffer J. V. Chymotrypsins. CRC Crit Rev Biochem. 1973 Apr;1(2):149–199. doi: 10.3109/10409237309102546. [DOI] [PubMed] [Google Scholar]
  9. Betzel C., Klupsch S., Papendorf G., Hastrup S., Branner S., Wilson K. S. Crystal structure of the alkaline proteinase Savinase from Bacillus lentus at 1.4 A resolution. J Mol Biol. 1992 Jan 20;223(2):427–445. doi: 10.1016/0022-2836(92)90662-4. [DOI] [PubMed] [Google Scholar]
  10. Betzel C., Pal G. P., Saenger W. Three-dimensional structure of proteinase K at 0.15-nm resolution. Eur J Biochem. 1988 Dec 1;178(1):155–171. doi: 10.1111/j.1432-1033.1988.tb14440.x. [DOI] [PubMed] [Google Scholar]
  11. Betzel C., Singh T. P., Visanji M., Peters K., Fittkau S., Saenger W., Wilson K. S. Structure of the complex of proteinase K with a substrate analogue hexapeptide inhibitor at 2.2-A resolution. J Biol Chem. 1993 Jul 25;268(21):15854–15858. [PubMed] [Google Scholar]
  12. Blow D. M., Birktoft J. J., Hartley B. S. Role of a buried acid group in the mechanism of action of chymotrypsin. Nature. 1969 Jan 25;221(5178):337–340. doi: 10.1038/221337a0. [DOI] [PubMed] [Google Scholar]
  13. Bode W., Chen Z., Bartels K., Kutzbach C., Schmidt-Kastner G., Bartunik H. Refined 2 A X-ray crystal structure of porcine pancreatic kallikrein A, a specific trypsin-like serine proteinase. Crystallization, structure determination, crystallographic refinement, structure and its comparison with bovine trypsin. J Mol Biol. 1983 Feb 25;164(2):237–282. doi: 10.1016/0022-2836(83)90077-3. [DOI] [PubMed] [Google Scholar]
  14. Bode W., Mayr I., Baumann U., Huber R., Stone S. R., Hofsteenge J. The refined 1.9 A crystal structure of human alpha-thrombin: interaction with D-Phe-Pro-Arg chloromethylketone and significance of the Tyr-Pro-Pro-Trp insertion segment. EMBO J. 1989 Nov;8(11):3467–3475. doi: 10.1002/j.1460-2075.1989.tb08511.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Bode W., Meyer E., Jr, Powers J. C. Human leukocyte and porcine pancreatic elastase: X-ray crystal structures, mechanism, substrate specificity, and mechanism-based inhibitors. Biochemistry. 1989 Mar 7;28(5):1951–1963. doi: 10.1021/bi00431a001. [DOI] [PubMed] [Google Scholar]
  16. Bode W., Walter J., Huber R., Wenzel H. R., Tschesche H. The refined 2.2-A (0.22-nm) X-ray crystal structure of the ternary complex formed by bovine trypsinogen, valine-valine and the Arg15 analogue of bovine pancreatic trypsin inhibitor. Eur J Biochem. 1984 Oct 1;144(1):185–190. doi: 10.1111/j.1432-1033.1984.tb08447.x. [DOI] [PubMed] [Google Scholar]
  17. Bone R., Agard D. A. Mutational remodeling of enzyme specificity. Methods Enzymol. 1991;202:643–671. doi: 10.1016/0076-6879(91)02030-d. [DOI] [PubMed] [Google Scholar]
  18. Bone R., Frank D., Kettner C. A., Agard D. A. Structural analysis of specificity: alpha-lytic protease complexes with analogues of reaction intermediates. Biochemistry. 1989 Sep 19;28(19):7600–7609. doi: 10.1021/bi00445a015. [DOI] [PubMed] [Google Scholar]
  19. Bone R., Fujishige A., Kettner C. A., Agard D. A. Structural basis for broad specificity in alpha-lytic protease mutants. Biochemistry. 1991 Oct 29;30(43):10388–10398. doi: 10.1021/bi00107a005. [DOI] [PubMed] [Google Scholar]
  20. Bone R., Shenvi A. B., Kettner C. A., Agard D. A. Serine protease mechanism: structure of an inhibitory complex of alpha-lytic protease and a tightly bound peptide boronic acid. Biochemistry. 1987 Dec 1;26(24):7609–7614. doi: 10.1021/bi00398a012. [DOI] [PubMed] [Google Scholar]
  21. Bone R., Silen J. L., Agard D. A. Structural plasticity broadens the specificity of an engineered protease. Nature. 1989 May 18;339(6221):191–195. doi: 10.1038/339191a0. [DOI] [PubMed] [Google Scholar]
  22. Brenner C., Fuller R. S. Structural and enzymatic characterization of a purified prohormone-processing enzyme: secreted, soluble Kex2 protease. Proc Natl Acad Sci U S A. 1992 Feb 1;89(3):922–926. doi: 10.1073/pnas.89.3.922. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Bryan P., Pantoliano M. W., Quill S. G., Hsiao H. Y., Poulos T. Site-directed mutagenesis and the role of the oxyanion hole in subtilisin. Proc Natl Acad Sci U S A. 1986 Jun;83(11):3743–3745. doi: 10.1073/pnas.83.11.3743. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. Caldwell J. W., Agard D. A., Kollman P. A. Free energy calculations on binding and catalysis by alpha-lytic protease: the role of substrate size in the P1 pocket. Proteins. 1991;10(2):140–148. doi: 10.1002/prot.340100207. [DOI] [PubMed] [Google Scholar]
  25. Caputo A., James M. N., Powers J. C., Hudig D., Bleackley R. C. Conversion of the substrate specificity of mouse proteinase granzyme B. Nat Struct Biol. 1994 Jun;1(6):364–367. doi: 10.1038/nsb0694-364. [DOI] [PubMed] [Google Scholar]
  26. Carter P., Abrahmsén L., Wells J. A. Probing the mechanism and improving the rate of substrate-assisted catalysis in subtilisin BPN'. Biochemistry. 1991 Jun 25;30(25):6142–6148. doi: 10.1021/bi00239a009. [DOI] [PubMed] [Google Scholar]
  27. Carter P., Nilsson B., Burnier J. P., Burdick D., Wells J. A. Engineering subtilisin BPN' for site-specific proteolysis. Proteins. 1989;6(3):240–248. doi: 10.1002/prot.340060306. [DOI] [PubMed] [Google Scholar]
  28. Carter P., Wells J. A. Dissecting the catalytic triad of a serine protease. Nature. 1988 Apr 7;332(6164):564–568. doi: 10.1038/332564a0. [DOI] [PubMed] [Google Scholar]
  29. Carter P., Wells J. A. Engineering enzyme specificity by "substrate-assisted catalysis". Science. 1987 Jul 24;237(4813):394–399. doi: 10.1126/science.3299704. [DOI] [PubMed] [Google Scholar]
  30. Carter P., Wells J. A. Functional interaction among catalytic residues in subtilisin BPN'. Proteins. 1990;7(4):335–342. doi: 10.1002/prot.340070405. [DOI] [PubMed] [Google Scholar]
  31. Chasan R., Anderson K. V. The role of easter, an apparent serine protease, in organizing the dorsal-ventral pattern of the Drosophila embryo. Cell. 1989 Feb 10;56(3):391–400. doi: 10.1016/0092-8674(89)90242-0. [DOI] [PubMed] [Google Scholar]
  32. Corey D. R., Shiau A. K., Yang Q., Janowski B. A., Craik C. S. Trypsin display on the surface of bacteriophage. Gene. 1993 Jun 15;128(1):129–134. doi: 10.1016/0378-1119(93)90163-w. [DOI] [PubMed] [Google Scholar]
  33. Craik C. S., Largman C., Fletcher T., Roczniak S., Barr P. J., Fletterick R., Rutter W. J. Redesigning trypsin: alteration of substrate specificity. Science. 1985 Apr 19;228(4697):291–297. doi: 10.1126/science.3838593. [DOI] [PubMed] [Google Scholar]
  34. Craik C. S., Roczniak S., Largman C., Rutter W. J. The catalytic role of the active site aspartic acid in serine proteases. Science. 1987 Aug 21;237(4817):909–913. doi: 10.1126/science.3303334. [DOI] [PubMed] [Google Scholar]
  35. Creemers J. W., Siezen R. J., Roebroek A. J., Ayoubi T. A., Huylebroeck D., Van de Ven W. J. Modulation of furin-mediated proprotein processing activity by site-directed mutagenesis. J Biol Chem. 1993 Oct 15;268(29):21826–21834. [PubMed] [Google Scholar]
  36. DIXON G. H., GO S., NEURATH H. Peptides combined with 14C-diisopropyl phosphoryl following degradation of 14C-DIP-trypsin with alpha-chymotrypsin. Biochim Biophys Acta. 1956 Jan;19(1):193–195. doi: 10.1016/0006-3002(56)90414-0. [DOI] [PubMed] [Google Scholar]
  37. Dancer S. J., Garratt R., Saldanha J., Jhoti H., Evans R. The epidermolytic toxins are serine proteases. FEBS Lett. 1990 Jul 30;268(1):129–132. doi: 10.1016/0014-5793(90)80990-z. [DOI] [PubMed] [Google Scholar]
  38. Davie E. W., Fujikawa K., Kisiel W. The coagulation cascade: initiation, maintenance, and regulation. Biochemistry. 1991 Oct 29;30(43):10363–10370. doi: 10.1021/bi00107a001. [DOI] [PubMed] [Google Scholar]
  39. Delbaere L. T., Brayer G. D., James M. N. The 2.8 A resolution structure of Streptomyces griseus protease B and its homology with alpha-chymotrypsin and Streptomyces griseus protease A. Can J Biochem. 1979 Feb;57(2):135–144. doi: 10.1139/o79-017. [DOI] [PubMed] [Google Scholar]
  40. Drapeau G. R. The primary structure of staphylococcal protease. Can J Biochem. 1978 Jun;56(6):534–544. doi: 10.1139/o78-082. [DOI] [PubMed] [Google Scholar]
  41. Eder J., Rheinnecker M., Fersht A. R. Hydrolysis of small peptide substrates parallels binding of chymotrypsin inhibitor 2 for mutants of subtilisin BPN'. FEBS Lett. 1993 Dec 13;335(3):349–352. doi: 10.1016/0014-5793(93)80417-s. [DOI] [PubMed] [Google Scholar]
  42. Estell D. A., Graycar T. P., Miller J. V., Powers D. B., Wells J. A., Burnier J. P., Ng P. G. Probing steric and hydrophobic effects on enzyme-substrate interactions by protein engineering. Science. 1986 Aug 8;233(4764):659–663. doi: 10.1126/science.233.4764.659. [DOI] [PubMed] [Google Scholar]
  43. Evnin L. B., Vásquez J. R., Craik C. S. Substrate specificity of trypsin investigated by using a genetic selection. Proc Natl Acad Sci U S A. 1990 Sep;87(17):6659–6663. doi: 10.1073/pnas.87.17.6659. [DOI] [PMC free article] [PubMed] [Google Scholar]
  44. Fujinaga M., Delbaere L. T., Brayer G. D., James M. N. Refined structure of alpha-lytic protease at 1.7 A resolution. Analysis of hydrogen bonding and solvent structure. J Mol Biol. 1985 Aug 5;184(3):479–502. doi: 10.1016/0022-2836(85)90296-7. [DOI] [PubMed] [Google Scholar]
  45. Fujinaga M., James M. N. Rat submaxillary gland serine protease, tonin. Structure solution and refinement at 1.8 A resolution. J Mol Biol. 1987 May 20;195(2):373–396. doi: 10.1016/0022-2836(87)90658-9. [DOI] [PubMed] [Google Scholar]
  46. Fuller R. S., Brake A., Thorner J. Yeast prohormone processing enzyme (KEX2 gene product) is a Ca2+-dependent serine protease. Proc Natl Acad Sci U S A. 1989 Mar;86(5):1434–1438. doi: 10.1073/pnas.86.5.1434. [DOI] [PMC free article] [PubMed] [Google Scholar]
  47. Graf L., Craik C. S., Patthy A., Roczniak S., Fletterick R. J., Rutter W. J. Selective alteration of substrate specificity by replacement of aspartic acid-189 with lysine in the binding pocket of trypsin. Biochemistry. 1987 May 5;26(9):2616–2623. doi: 10.1021/bi00383a031. [DOI] [PubMed] [Google Scholar]
  48. Graham L. D., Haggett K. D., Jennings P. A., Le Brocque D. S., Whittaker R. G., Schober P. A. Random mutagenesis of the substrate-binding site of a serine protease can generate enzymes with increased activities and altered primary specificities. Biochemistry. 1993 Jun 22;32(24):6250–6258. doi: 10.1021/bi00075a019. [DOI] [PubMed] [Google Scholar]
  49. Grant G. A., Eisen A. Z. Substrate specificity of the collagenolytic serine protease from Uca pugilator: studies with noncollagenous substrates. Biochemistry. 1980 Dec 23;19(26):6089–6095. doi: 10.1021/bi00567a022. [DOI] [PubMed] [Google Scholar]
  50. Grant G. A., Henderson K. O., Eisen A. Z., Bradshaw R. A. Amino acid sequence of a collagenolytic protease from the hepatopancreas of the fiddler crab, Uca pugilator. Biochemistry. 1980 Sep 30;19(20):4653–4659. doi: 10.1021/bi00561a018. [DOI] [PubMed] [Google Scholar]
  51. Greer J. Comparative modeling methods: application to the family of the mammalian serine proteases. Proteins. 1990;7(4):317–334. doi: 10.1002/prot.340070404. [DOI] [PubMed] [Google Scholar]
  52. Gros P., Betzel C., Dauter Z., Wilson K. S., Hol W. G. Molecular dynamics refinement of a thermitase-eglin-c complex at 1.98 A resolution and comparison of two crystal forms that differ in calcium content. J Mol Biol. 1989 Nov 20;210(2):347–367. doi: 10.1016/0022-2836(89)90336-7. [DOI] [PubMed] [Google Scholar]
  53. Gráf L., Jancsó A., Szilágyi L., Hegyi G., Pintér K., Náray-Szabó G., Hepp J., Medzihradszky K., Rutter W. J. Electrostatic complementarity within the substrate-binding pocket of trypsin. Proc Natl Acad Sci U S A. 1988 Jul;85(14):4961–4965. doi: 10.1073/pnas.85.14.4961. [DOI] [PMC free article] [PubMed] [Google Scholar]
  54. Grøn H., Breddam K. Interdependency of the binding subsites in subtilisin. Biochemistry. 1992 Sep 22;31(37):8967–8971. doi: 10.1021/bi00152a037. [DOI] [PubMed] [Google Scholar]
  55. Grøn H., Meldal M., Breddam K. Extensive comparison of the substrate preferences of two subtilisins as determined with peptide substrates which are based on the principle of intramolecular quenching. Biochemistry. 1992 Jul 7;31(26):6011–6018. doi: 10.1021/bi00141a008. [DOI] [PubMed] [Google Scholar]
  56. Harper J. W., Cook R. R., Roberts C. J., McLaughlin B. J., Powers J. C. Active site mapping of the serine proteases human leukocyte elastase, cathepsin G, porcine pancreatic elastase, rat mast cell proteases I and II. Bovine chymotrypsin A alpha, and Staphylococcus aureus protease V-8 using tripeptide thiobenzyl ester substrates. Biochemistry. 1984 Jun 19;23(13):2995–3002. doi: 10.1021/bi00308a023. [DOI] [PubMed] [Google Scholar]
  57. Hedstrom L., Farr-Jones S., Kettner C. A., Rutter W. J. Converting trypsin to chymotrypsin: ground-state binding does not determine substrate specificity. Biochemistry. 1994 Jul 26;33(29):8764–8769. doi: 10.1021/bi00195a018. [DOI] [PubMed] [Google Scholar]
  58. Hedstrom L., Szilagyi L., Rutter W. J. Converting trypsin to chymotrypsin: the role of surface loops. Science. 1992 Mar 6;255(5049):1249–1253. doi: 10.1126/science.1546324. [DOI] [PubMed] [Google Scholar]
  59. Higaki J. N., Evnin L. B., Craik C. S. Introduction of a cysteine protease active site into trypsin. Biochemistry. 1989 Nov 28;28(24):9256–9263. doi: 10.1021/bi00450a004. [DOI] [PubMed] [Google Scholar]
  60. Higaki J. N., Haymore B. L., Chen S., Fletterick R. J., Craik C. S. Regulation of serine protease activity by an engineered metal switch. Biochemistry. 1990 Sep 18;29(37):8582–8586. doi: 10.1021/bi00489a012. [DOI] [PubMed] [Google Scholar]
  61. Horrevoets A. J., Tans G., Smilde A. E., van Zonneveld A. J., Pannekoek H. Thrombin-variable region 1 (VR1). Evidence for the dominant contribution of VR1 of serine proteases to their interaction with plasminogen activator inhibitor 1. J Biol Chem. 1993 Jan 15;268(2):779–782. [PubMed] [Google Scholar]
  62. Hwang J. K., Warshel A. Why ion pair reversal by protein engineering is unlikely to succeed. Nature. 1988 Jul 21;334(6179):270–272. doi: 10.1038/334270a0. [DOI] [PubMed] [Google Scholar]
  63. Jackson D. Y., Burnier J., Quan C., Stanley M., Tom J., Wells J. A. A designed peptide ligase for total synthesis of ribonuclease A with unnatural catalytic residues. Science. 1994 Oct 14;266(5183):243–247. doi: 10.1126/science.7939659. [DOI] [PubMed] [Google Scholar]
  64. Jackson S. E., Fersht A. R. Contribution of long-range electrostatic interactions to the stabilization of the catalytic transition state of the serine protease subtilisin BPN'. Biochemistry. 1993 Dec 21;32(50):13909–13916. doi: 10.1021/bi00213a021. [DOI] [PubMed] [Google Scholar]
  65. Joachimiak A., Haran T. E., Sigler P. B. Mutagenesis supports water mediated recognition in the trp repressor-operator system. EMBO J. 1994 Jan 15;13(2):367–372. doi: 10.1002/j.1460-2075.1994.tb06270.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  66. Kabsch W., Sander C. Dictionary of protein secondary structure: pattern recognition of hydrogen-bonded and geometrical features. Biopolymers. 1983 Dec;22(12):2577–2637. doi: 10.1002/bip.360221211. [DOI] [PubMed] [Google Scholar]
  67. Kettner C. A., Shenvi A. B. Inhibition of the serine proteases leukocyte elastase, pancreatic elastase, cathepsin G, and chymotrypsin by peptide boronic acids. J Biol Chem. 1984 Dec 25;259(24):15106–15114. [PubMed] [Google Scholar]
  68. Kossiakoff A. A., Spencer S. A. Direct determination of the protonation states of aspartic acid-102 and histidine-57 in the tetrahedral intermediate of the serine proteases: neutron structure of trypsin. Biochemistry. 1981 Oct 27;20(22):6462–6474. doi: 10.1021/bi00525a027. [DOI] [PubMed] [Google Scholar]
  69. Kraut J. Serine proteases: structure and mechanism of catalysis. Annu Rev Biochem. 1977;46:331–358. doi: 10.1146/annurev.bi.46.070177.001555. [DOI] [PubMed] [Google Scholar]
  70. LaVallie E. R., Rehemtulla A., Racie L. A., DiBlasio E. A., Ferenz C., Grant K. L., Light A., McCoy J. M. Cloning and functional expression of a cDNA encoding the catalytic subunit of bovine enterokinase. J Biol Chem. 1993 Nov 5;268(31):23311–23317. [PubMed] [Google Scholar]
  71. Lazure C., Seidah N. G., Pélaprat D., Chrétien M. Proteases and posttranslational processing of prohormones: a review. Can J Biochem Cell Biol. 1983 Jul;61(7):501–515. doi: 10.1139/o83-066. [DOI] [PubMed] [Google Scholar]
  72. Le Trong H., Neurath H., Woodbury R. G. Substrate specificity of the chymotrypsin-like protease in secretory granules isolated from rat mast cells. Proc Natl Acad Sci U S A. 1987 Jan;84(2):364–367. doi: 10.1073/pnas.84.2.364. [DOI] [PMC free article] [PubMed] [Google Scholar]
  73. Le Trong H., Parmelee D. C., Walsh K. A., Neurath H., Woodbury R. G. Amino acid sequence of rat mast cell protease I (chymase). Biochemistry. 1987 Nov 3;26(22):6988–6994. doi: 10.1021/bi00396a020. [DOI] [PubMed] [Google Scholar]
  74. Liao D. I., Breddam K., Sweet R. M., Bullock T., Remington S. J. Refined atomic model of wheat serine carboxypeptidase II at 2.2-A resolution. Biochemistry. 1992 Oct 13;31(40):9796–9812. doi: 10.1021/bi00155a037. [DOI] [PubMed] [Google Scholar]
  75. Liao D. I., Remington S. J. Structure of wheat serine carboxypeptidase II at 3.5-A resolution. A new class of serine proteinase. J Biol Chem. 1990 Apr 25;265(12):6528–6531. doi: 10.2210/pdb2sc2/pdb. [DOI] [PubMed] [Google Scholar]
  76. Light A., Fonseca P. The preparation and properties of the catalytic subunit of bovine enterokinase. J Biol Chem. 1984 Nov 10;259(21):13195–13198. [PubMed] [Google Scholar]
  77. Lobe C. G., Finlay B. B., Paranchych W., Paetkau V. H., Bleackley R. C. Novel serine proteases encoded by two cytotoxic T lymphocyte-specific genes. Science. 1986 May 16;232(4752):858–861. doi: 10.1126/science.3518058. [DOI] [PubMed] [Google Scholar]
  78. Loewenthal R., Sancho J., Reinikainen T., Fersht A. R. Long-range surface charge-charge interactions in proteins. Comparison of experimental results with calculations from a theoretical method. J Mol Biol. 1993 Jul 20;232(2):574–583. doi: 10.1006/jmbi.1993.1412. [DOI] [PubMed] [Google Scholar]
  79. Madison E. L., Goldsmith E. J., Gerard R. D., Gething M. J., Sambrook J. F., Bassel-Duby R. S. Amino acid residues that affect interaction of tissue-type plasminogen activator with plasminogen activator inhibitor 1. Proc Natl Acad Sci U S A. 1990 May;87(9):3530–3533. doi: 10.1073/pnas.87.9.3530. [DOI] [PMC free article] [PubMed] [Google Scholar]
  80. Magee A. I., Grant D. A., Hermon-Taylor J. The apparent molecular weights of human intestinal aminopeptidase, enterokinase and maltase in native duodenal fluid. Biochem J. 1977 Sep 1;165(3):583–585. doi: 10.1042/bj1650583. [DOI] [PMC free article] [PubMed] [Google Scholar]
  81. Maroux S., Baratti J., Desnuelle P. Purification and specificity of porcine enterokinase. J Biol Chem. 1971 Aug 25;246(16):5031–5039. [PubMed] [Google Scholar]
  82. Matthews B. W., Sigler P. B., Henderson R., Blow D. M. Three-dimensional structure of tosyl-alpha-chymotrypsin. Nature. 1967 May 13;214(5089):652–656. doi: 10.1038/214652a0. [DOI] [PubMed] [Google Scholar]
  83. Matthews D. J., Wells J. A. Substrate phage: selection of protease substrates by monovalent phage display. Science. 1993 May 21;260(5111):1113–1117. doi: 10.1126/science.8493554. [DOI] [PubMed] [Google Scholar]
  84. Matthews G., Shennan K. I., Seal A. J., Taylor N. A., Colman A., Docherty K. Autocatalytic maturation of the prohormone convertase PC2. J Biol Chem. 1994 Jan 7;269(1):588–592. [PubMed] [Google Scholar]
  85. McGrath M. E., Haymore B. L., Summers N. L., Craik C. S., Fletterick R. J. Structure of an engineered, metal-actuated switch in trypsin. Biochemistry. 1993 Mar 2;32(8):1914–1919. doi: 10.1021/bi00059a005. [DOI] [PubMed] [Google Scholar]
  86. McGrath M. E., Vásquez J. R., Craik C. S., Yang A. S., Honig B., Fletterick R. J. Perturbing the polar environment of Asp102 in trypsin: consequences of replacing conserved Ser214. Biochemistry. 1992 Mar 31;31(12):3059–3064. doi: 10.1021/bi00127a005. [DOI] [PubMed] [Google Scholar]
  87. McGrath M. E., Wilke M. E., Higaki J. N., Craik C. S., Fletterick R. J. Crystal structures of two engineered thiol trypsins. Biochemistry. 1989 Nov 28;28(24):9264–9270. doi: 10.1021/bi00450a005. [DOI] [PubMed] [Google Scholar]
  88. McPhalen C. A., James M. N. Structural comparison of two serine proteinase-protein inhibitor complexes: eglin-c-subtilisin Carlsberg and CI-2-subtilisin Novo. Biochemistry. 1988 Aug 23;27(17):6582–6598. [PubMed] [Google Scholar]
  89. Mizushima N., Spellmeyer D., Hirono S., Pearlman D., Kollman P. Free energy perturbation calculations on binding and catalysis after mutating threonine 220 in subtilisin. J Biol Chem. 1991 Jun 25;266(18):11801–11809. [PubMed] [Google Scholar]
  90. Mortensen U. H., Remington S. J., Breddam K. Site-directed mutagenesis on (serine) carboxypeptidase Y. A hydrogen bond network stabilizes the transition state by interaction with the C-terminal carboxylate group of the substrate. Biochemistry. 1994 Jan 18;33(2):508–517. doi: 10.1021/bi00168a016. [DOI] [PubMed] [Google Scholar]
  91. Moult J., Sussman F., James M. N. Electron density calculations as an extension of protein structure refinement. Streptomyces griseus protease A at 1.5 A resolution. J Mol Biol. 1985 Apr 20;182(4):555–566. doi: 10.1016/0022-2836(85)90241-4. [DOI] [PubMed] [Google Scholar]
  92. Murphy M. E., Moult J., Bleackley R. C., Gershenfeld H., Weissman I. L., James M. N. Comparative molecular model building of two serine proteinases from cytotoxic T lymphocytes. Proteins. 1988;4(3):190–204. doi: 10.1002/prot.340040306. [DOI] [PubMed] [Google Scholar]
  93. Narayana S. V., Carson M., el-Kabbani O., Kilpatrick J. M., Moore D., Chen X., Bugg C. E., Volanakis J. E., DeLucas L. J. Structure of human factor D. A complement system protein at 2.0 A resolution. J Mol Biol. 1994 Jan 14;235(2):695–708. doi: 10.1006/jmbi.1994.1021. [DOI] [PubMed] [Google Scholar]
  94. Neurath H. Evolution of proteolytic enzymes. Science. 1984 Apr 27;224(4647):350–357. doi: 10.1126/science.6369538. [DOI] [PubMed] [Google Scholar]
  95. Nienaber V. L., Breddam K., Birktoft J. J. A glutamic acid specific serine protease utilizes a novel histidine triad in substrate binding. Biochemistry. 1993 Nov 2;32(43):11469–11475. doi: 10.1021/bi00094a001. [DOI] [PubMed] [Google Scholar]
  96. Ny T., Sawdey M., Lawrence D., Millan J. L., Loskutoff D. J. Cloning and sequence of a cDNA coding for the human beta-migrating endothelial-cell-type plasminogen activator inhibitor. Proc Natl Acad Sci U S A. 1986 Sep;83(18):6776–6780. doi: 10.1073/pnas.83.18.6776. [DOI] [PMC free article] [PubMed] [Google Scholar]
  97. Odake S., Kam C. M., Narasimhan L., Poe M., Blake J. T., Krahenbuhl O., Tschopp J., Powers J. C. Human and murine cytotoxic T lymphocyte serine proteases: subsite mapping with peptide thioester substrates and inhibition of enzyme activity and cytolysis by isocoumarins. Biochemistry. 1991 Feb 26;30(8):2217–2227. doi: 10.1021/bi00222a027. [DOI] [PubMed] [Google Scholar]
  98. Ollis D. L., Cheah E., Cygler M., Dijkstra B., Frolow F., Franken S. M., Harel M., Remington S. J., Silman I., Schrag J. The alpha/beta hydrolase fold. Protein Eng. 1992 Apr;5(3):197–211. doi: 10.1093/protein/5.3.197. [DOI] [PubMed] [Google Scholar]
  99. Otwinowski Z., Schevitz R. W., Zhang R. G., Lawson C. L., Joachimiak A., Marmorstein R. Q., Luisi B. F., Sigler P. B. Crystal structure of trp repressor/operator complex at atomic resolution. Nature. 1988 Sep 22;335(6188):321–329. doi: 10.1038/335321a0. [DOI] [PubMed] [Google Scholar]
  100. Padmanabhan K., Padmanabhan K. P., Tulinsky A., Park C. H., Bode W., Huber R., Blankenship D. T., Cardin A. D., Kisiel W. Structure of human des(1-45) factor Xa at 2.2 A resolution. J Mol Biol. 1993 Aug 5;232(3):947–966. doi: 10.1006/jmbi.1993.1441. [DOI] [PubMed] [Google Scholar]
  101. Perona J. J., Evnin L. B., Craik C. S. A genetic selection elucidates structural determinants of arginine versus lysine specificity in trypsin. Gene. 1993 Dec 27;137(1):121–126. doi: 10.1016/0378-1119(93)90259-6. [DOI] [PubMed] [Google Scholar]
  102. Perona J. J., Hedstrom L., Rutter W. J., Fletterick R. J. Structural origins of substrate discrimination in trypsin and chymotrypsin. Biochemistry. 1995 Feb 7;34(5):1489–1499. doi: 10.1021/bi00005a004. [DOI] [PubMed] [Google Scholar]
  103. Perona J. J., Hedstrom L., Wagner R. L., Rutter W. J., Craik C. S., Fletterick R. J. Exogenous acetate reconstitutes the enzymatic activity of trypsin Asp189Ser. Biochemistry. 1994 Mar 22;33(11):3252–3259. doi: 10.1021/bi00177a016. [DOI] [PubMed] [Google Scholar]
  104. Perona J. J., Tsu C. A., Craik C. S., Fletterick R. J. Crystal structures of rat anionic trypsin complexed with the protein inhibitors APPI and BPTI. J Mol Biol. 1993 Apr 5;230(3):919–933. doi: 10.1006/jmbi.1993.1210. [DOI] [PubMed] [Google Scholar]
  105. Perona J. J., Tsu C. A., McGrath M. E., Craik C. S., Fletterick R. J. Relocating a negative charge in the binding pocket of trypsin. J Mol Biol. 1993 Apr 5;230(3):934–949. doi: 10.1006/jmbi.1993.1211. [DOI] [PubMed] [Google Scholar]
  106. Polgar L. pH-dependent mechanism in the catalysis of prolyl endopeptidase from pig muscle. Eur J Biochem. 1991 Apr 23;197(2):441–447. doi: 10.1111/j.1432-1033.1991.tb15930.x. [DOI] [PubMed] [Google Scholar]
  107. Poulos T. L., Alden R. A., Freer S. T., Birktoft J. J., Kraut J. Polypeptide halomethyl ketones bind to serine proteases as analogs of the tetrahedral intermediate. X-ray crystallographic comparison of lysine- and phenylalanine-polypeptide chloromethyl ketone-inhibited subtilisin. J Biol Chem. 1976 Feb 25;251(4):1097–1103. [PubMed] [Google Scholar]
  108. Powers J. C., Tanaka T., Harper J. W., Minematsu Y., Barker L., Lincoln D., Crumley K. V., Fraki J. E., Schechter N. M., Lazarus G. G. Mammalian chymotrypsin-like enzymes. Comparative reactivities of rat mast cell proteases, human and dog skin chymases, and human cathepsin G with peptide 4-nitroanilide substrates and with peptide chloromethyl ketone and sulfonyl fluoride inhibitors. Biochemistry. 1985 Apr 9;24(8):2048–2058. doi: 10.1021/bi00329a037. [DOI] [PubMed] [Google Scholar]
  109. Rao S. N., Singh U. C., Bash P. A., Kollman P. A. Free energy perturbation calculations on binding and catalysis after mutating Asn 155 in subtilisin. Nature. 1987 Aug 6;328(6130):551–554. doi: 10.1038/328551a0. [DOI] [PubMed] [Google Scholar]
  110. Read R. J., James M. N. Refined crystal structure of Streptomyces griseus trypsin at 1.7 A resolution. J Mol Biol. 1988 Apr 5;200(3):523–551. doi: 10.1016/0022-2836(88)90541-4. [DOI] [PubMed] [Google Scholar]
  111. Rehemtulla A., Barr P. J., Rhodes C. J., Kaufman R. J. PACE4 is a member of the mammalian propeptidase family that has overlapping but not identical substrate specificity to PACE. Biochemistry. 1993 Nov 2;32(43):11586–11590. doi: 10.1021/bi00094a015. [DOI] [PubMed] [Google Scholar]
  112. Remington S. J., Woodbury R. G., Reynolds R. A., Matthews B. W., Neurath H. The structure of rat mast cell protease II at 1.9-A resolution. Biochemistry. 1988 Oct 18;27(21):8097–8105. doi: 10.1021/bi00421a019. [DOI] [PubMed] [Google Scholar]
  113. Rheinnecker M., Baker G., Eder J., Fersht A. R. Engineering a novel specificity in subtilisin BPN'. Biochemistry. 1993 Feb 9;32(5):1199–1203. doi: 10.1021/bi00056a001. [DOI] [PubMed] [Google Scholar]
  114. Rheinnecker M., Eder J., Pandey P. S., Fersht A. R. Variants of subtilisin BPN' with altered specificity profiles. Biochemistry. 1994 Jan 11;33(1):221–225. doi: 10.1021/bi00167a029. [DOI] [PubMed] [Google Scholar]
  115. Robertus J. D., Alden R. A., Birktoft J. J., Kraut J., Powers J. C., Wilcox P. E. An x-ray crystallographic study of the binding of peptide chloromethyl ketone inhibitors to subtilisin BPN'. Biochemistry. 1972 Jun 20;11(13):2439–2449. doi: 10.1021/bi00763a009. [DOI] [PubMed] [Google Scholar]
  116. Robertus J. D., Kraut J., Alden R. A., Birktoft J. J. Subtilisin; a stereochemical mechanism involving transition-state stabilization. Biochemistry. 1972 Nov 7;11(23):4293–4303. doi: 10.1021/bi00773a016. [DOI] [PubMed] [Google Scholar]
  117. Rose G. D., Creamer T. P. Protein folding: predicting predicting. Proteins. 1994 May;19(1):1–3. doi: 10.1002/prot.340190102. [DOI] [PubMed] [Google Scholar]
  118. Russell A. J., Thomas P. G., Fersht A. R. Electrostatic effects on modification of charged groups in the active site cleft of subtilisin by protein engineering. J Mol Biol. 1987 Feb 20;193(4):803–813. doi: 10.1016/0022-2836(87)90360-3. [DOI] [PubMed] [Google Scholar]
  119. Rühlmann A., Kukla D., Schwager P., Bartels K., Huber R. Structure of the complex formed by bovine trypsin and bovine pancreatic trypsin inhibitor. Crystal structure determination and stereochemistry of the contact region. J Mol Biol. 1973 Jul 5;77(3):417–436. doi: 10.1016/0022-2836(73)90448-8. [DOI] [PubMed] [Google Scholar]
  120. Salvesen G., Farley D., Shuman J., Przybyla A., Reilly C., Travis J. Molecular cloning of human cathepsin G: structural similarity to mast cell and cytotoxic T lymphocyte proteinases. Biochemistry. 1987 Apr 21;26(8):2289–2293. doi: 10.1021/bi00382a032. [DOI] [PubMed] [Google Scholar]
  121. Schechter I., Berger A. On the size of the active site in proteases. I. Papain. Biochem Biophys Res Commun. 1967 Apr 20;27(2):157–162. doi: 10.1016/s0006-291x(67)80055-x. [DOI] [PubMed] [Google Scholar]
  122. Schellenberger V., Turck C. W., Hedstrom L., Rutter W. J. Mapping the S' subsites of serine proteases using acyl transfer to mixtures of peptide nucleophiles. Biochemistry. 1993 Apr 27;32(16):4349–4353. doi: 10.1021/bi00067a026. [DOI] [PubMed] [Google Scholar]
  123. Schellenberger V., Turck C. W., Rutter W. J. Role of the S' subsites in serine protease catalysis. Active-site mapping of rat chymotrypsin, rat trypsin, alpha-lytic protease, and cercarial protease from Schistosoma mansoni. Biochemistry. 1994 Apr 12;33(14):4251–4257. doi: 10.1021/bi00180a020. [DOI] [PubMed] [Google Scholar]
  124. Seidah N. G., Day R., Marcinkiewicz M., Benjannet S., Chrétien M. Mammalian neural and endocrine pro-protein and pro-hormone convertases belonging to the subtilisin family of serine proteinases. Enzyme. 1991;45(5-6):271–284. doi: 10.1159/000468901. [DOI] [PubMed] [Google Scholar]
  125. Sellos D., Van Wormhoudt A. Molecular cloning of a cDNA that encodes a serine protease with chymotryptic and collagenolytic activities in the hepatopancreas of the shrimp Penaeus vanameii (Crustacea, Decapoda). FEBS Lett. 1992 Sep 14;309(3):219–224. doi: 10.1016/0014-5793(92)80777-e. [DOI] [PubMed] [Google Scholar]
  126. Shakked Z., Guzikevich-Guerstein G., Frolow F., Rabinovich D., Joachimiak A., Sigler P. B. Determinants of repressor/operator recognition from the structure of the trp operator binding site. Nature. 1994 Mar 31;368(6470):469–473. doi: 10.1038/368469a0. [DOI] [PubMed] [Google Scholar]
  127. Siezen R. J., Bruinenberg P. G., Vos P., van Alen-Boerrigter I., Nijhuis M., Alting A. C., Exterkate F. A., de Vos W. M. Engineering of the substrate-binding region of the subtilisin-like, cell-envelope proteinase of Lactococcus lactis. Protein Eng. 1993 Nov;6(8):927–937. doi: 10.1093/protein/6.8.927. [DOI] [PubMed] [Google Scholar]
  128. Sinha S., Watorek W., Karr S., Giles J., Bode W., Travis J. Primary structure of human neutrophil elastase. Proc Natl Acad Sci U S A. 1987 Apr;84(8):2228–2232. doi: 10.1073/pnas.84.8.2228. [DOI] [PMC free article] [PubMed] [Google Scholar]
  129. Smeekens S. P., Avruch A. S., LaMendola J., Chan S. J., Steiner D. F. Identification of a cDNA encoding a second putative prohormone convertase related to PC2 in AtT20 cells and islets of Langerhans. Proc Natl Acad Sci U S A. 1991 Jan 15;88(2):340–344. doi: 10.1073/pnas.88.2.340. [DOI] [PMC free article] [PubMed] [Google Scholar]
  130. Smith C. L., DeLotto R. Ventralizing signal determined by protease activation in Drosophila embryogenesis. Nature. 1994 Apr 7;368(6471):548–551. doi: 10.1038/368548a0. [DOI] [PubMed] [Google Scholar]
  131. Sprang S., Standing T., Fletterick R. J., Stroud R. M., Finer-Moore J., Xuong N. H., Hamlin R., Rutter W. J., Craik C. S. The three-dimensional structure of Asn102 mutant of trypsin: role of Asp102 in serine protease catalysis. Science. 1987 Aug 21;237(4817):905–909. doi: 10.1126/science.3112942. [DOI] [PubMed] [Google Scholar]
  132. Stein R. L., Strimpler A. M., Hori H., Powers J. C. Catalysis by human leukocyte elastase: proton inventory as a mechanistic probe. Biochemistry. 1987 Mar 10;26(5):1305–1314. doi: 10.1021/bi00379a016. [DOI] [PubMed] [Google Scholar]
  133. Steitz T. A., Shulman R. G. Crystallographic and NMR studies of the serine proteases. Annu Rev Biophys Bioeng. 1982;11:419–444. doi: 10.1146/annurev.bb.11.060182.002223. [DOI] [PubMed] [Google Scholar]
  134. Stroud R. M. A family of protein-cutting proteins. Sci Am. 1974 Jul;231(1):74–88. doi: 10.1038/scientificamerican0774-74. [DOI] [PubMed] [Google Scholar]
  135. Svendsen I., Jensen M. R., Breddam K. The primary structure of the glutamic acid-specific protease of Streptomyces griseus. FEBS Lett. 1991 Nov 4;292(1-2):165–167. doi: 10.1016/0014-5793(91)80859-2. [DOI] [PubMed] [Google Scholar]
  136. Sørensen S. B., Bech L. M., Meldal M., Breddam K. Mutational replacements of the amino acid residues forming the hydrophobic S4 binding pocket of subtilisin 309 from Bacillus lentus. Biochemistry. 1993 Sep 7;32(35):8994–8999. doi: 10.1021/bi00086a003. [DOI] [PubMed] [Google Scholar]
  137. Takeuchi Y., Noguchi S., Satow Y., Kojima S., Kumagai I., Miura K., Nakamura K. T., Mitsui Y. Molecular recognition at the active site of subtilisin BPN': crystallographic studies using genetically engineered proteinaceous inhibitor SSI (Streptomyces subtilisin inhibitor). Protein Eng. 1991 Jun;4(5):501–508. doi: 10.1093/protein/4.5.501. [DOI] [PubMed] [Google Scholar]
  138. Teplyakov A. V., van der Laan J. M., Lammers A. A., Kelders H., Kalk K. H., Misset O., Mulleners L. J., Dijkstra B. W. Protein engineering of the high-alkaline serine protease PB92 from Bacillus alcalophilus: functional and structural consequences of mutation at the S4 substrate binding pocket. Protein Eng. 1992 Jul;5(5):413–420. doi: 10.1093/protein/5.5.413. [DOI] [PubMed] [Google Scholar]
  139. Thompson R. C., Blout E. R. Evidence for an extended active center in elastase. Proc Natl Acad Sci U S A. 1970 Dec;67(4):1734–1740. doi: 10.1073/pnas.67.4.1734. [DOI] [PMC free article] [PubMed] [Google Scholar]
  140. Tsu C. A., Perona J. J., Schellenberger V., Turck C. W., Craik C. S. The substrate specificity of Uca pugilator collagenolytic serine protease 1 correlates with the bovine type I collagen cleavage sites. J Biol Chem. 1994 Jul 29;269(30):19565–19572. [PubMed] [Google Scholar]
  141. Van de Ven W. J., Roebroek A. J., Van Duijnhoven H. L. Structure and function of eukaryotic proprotein processing enzymes of the subtilisin family of serine proteases. Crit Rev Oncog. 1993;4(2):115–136. [PubMed] [Google Scholar]
  142. Warshel A., Naray-Szabo G., Sussman F., Hwang J. K. How do serine proteases really work? Biochemistry. 1989 May 2;28(9):3629–3637. doi: 10.1021/bi00435a001. [DOI] [PubMed] [Google Scholar]
  143. Watson H. C., Shotton D. M., Cox J. M., Muirhead H. Three-dimensional Fourier synthesis of tosyl-elastase at 3.5 å resolution. Nature. 1970 Feb 28;225(5235):806–811. doi: 10.1038/225806a0. [DOI] [PubMed] [Google Scholar]
  144. Wei A. Z., Mayr I., Bode W. The refined 2.3 A crystal structure of human leukocyte elastase in a complex with a valine chloromethyl ketone inhibitor. FEBS Lett. 1988 Jul 18;234(2):367–373. doi: 10.1016/0014-5793(88)80118-2. [DOI] [PubMed] [Google Scholar]
  145. Wells J. A., Cunningham B. C., Graycar T. P., Estell D. A. Recruitment of substrate-specificity properties from one enzyme into a related one by protein engineering. Proc Natl Acad Sci U S A. 1987 Aug;84(15):5167–5171. doi: 10.1073/pnas.84.15.5167. [DOI] [PMC free article] [PubMed] [Google Scholar]
  146. Wells J. A., Estell D. A. Subtilisin--an enzyme designed to be engineered. Trends Biochem Sci. 1988 Aug;13(8):291–297. doi: 10.1016/0968-0004(88)90121-1. [DOI] [PubMed] [Google Scholar]
  147. Wells J. A., Powers D. B., Bott R. R., Graycar T. P., Estell D. A. Designing substrate specificity by protein engineering of electrostatic interactions. Proc Natl Acad Sci U S A. 1987 Mar;84(5):1219–1223. doi: 10.1073/pnas.84.5.1219. [DOI] [PMC free article] [PubMed] [Google Scholar]
  148. Wilke M. E., Higaki J. N., Craik C. S., Fletterick R. J. Crystallographic analysis of trypsin-G226A. A specificity pocket mutant of rat trypsin with altered binding and catalysis. J Mol Biol. 1991 Jun 5;219(3):525–532. doi: 10.1016/0022-2836(91)90191-8. [DOI] [PubMed] [Google Scholar]
  149. Wilson C., Mace J. E., Agard D. A. Computational method for the design of enzymes with altered substrate specificity. J Mol Biol. 1991 Jul 20;220(2):495–506. doi: 10.1016/0022-2836(91)90026-3. [DOI] [PubMed] [Google Scholar]
  150. Woodbury R. G., Everitt M., Sanada Y., Katunuma N., Lagunoff D., Neurath H. A major serine protease in rat skeletal muscle: evidence for its mast cell origin. Proc Natl Acad Sci U S A. 1978 Nov;75(11):5311–5313. doi: 10.1073/pnas.75.11.5311. [DOI] [PMC free article] [PubMed] [Google Scholar]
  151. Woodbury R. G., Gruzenski G. M., Lagunoff D. Immunofluorescent localization of a serine protease in rat small intestine. Proc Natl Acad Sci U S A. 1978 Jun;75(6):2785–2789. doi: 10.1073/pnas.75.6.2785. [DOI] [PMC free article] [PubMed] [Google Scholar]
  152. Wright C. S., Alden R. A., Kraut J. Structure of subtilisin BPN' at 2.5 angström resolution. Nature. 1969 Jan 18;221(5177):235–242. doi: 10.1038/221235a0. [DOI] [PubMed] [Google Scholar]
  153. Yoshida N., Everitt M. T., Neurath H., Woodbury R. G., Powers J. C. Substrate specificity of two chymotrypsin-like proteases from rat mast cells. Studies with peptide 4-nitroanilides and comparison with cathepsin G. Biochemistry. 1980 Dec 9;19(25):5799–5804. doi: 10.1021/bi00566a021. [DOI] [PubMed] [Google Scholar]
  154. Zhou G. W., Guo J., Huang W., Fletterick R. J., Scanlan T. S. Crystal structure of a catalytic antibody with a serine protease active site. Science. 1994 Aug 19;265(5175):1059–1064. doi: 10.1126/science.8066444. [DOI] [PubMed] [Google Scholar]
  155. van den Ouweland A. M., van Duijnhoven H. L., Keizer G. D., Dorssers L. C., Van de Ven W. J. Structural homology between the human fur gene product and the subtilisin-like protease encoded by yeast KEX2. Nucleic Acids Res. 1990 Feb 11;18(3):664–664. doi: 10.1093/nar/18.3.664. [DOI] [PMC free article] [PubMed] [Google Scholar]

Articles from Protein Science : A Publication of the Protein Society are provided here courtesy of The Protein Society

RESOURCES