Skip to main content
PMC home page
Biophysical Journal logoLink to Biophysical Journal
. 2001 Feb;80(2):789–800. doi: 10.1016/S0006-3495(01)76058-4

Toward understanding interfacial activation of secretory phospholipase A2 (PLA2): membrane surface properties and membrane-induced structural changes in the enzyme contribute synergistically to PLA2 activation.

S A Tatulian 1
PMCID: PMC1301277  PMID: 11159446

Abstract

Phospholipase A2 (PLA2) hydrolyzes phospholipids to free fatty acids and lysolipids and thus initiates the biosynthesis of eicosanoids and platelet-activating factor, potent mediators of inflammation, allergy, apoptosis, and tumorigenesis. The relative contributions of the physical properties of membranes and the structural changes in PLA2 to the interfacial activation of PLA2, that is, a strong increase in the lipolytic activity upon binding to the surface of phospholipid membranes or micelles, are not well understood. The present results demonstrate that both binding of PLA2 to phospholipid bilayers and its activity are facilitated by membrane surface electrostatics. Higher PLA2 activity toward negatively charged membranes is shown to result from stronger membrane-enzyme electrostatic interactions rather than selective hydrolysis of the acidic lipid. Phospholipid hydrolysis by PLA2 is followed by preferential removal of the liberated lysolipid and accumulation of the fatty acid in the membrane that may predominantly modulate PLA2 activity by affecting membrane electrostatics and/or morphology. The previously described induction of a flexible helical structure in PLA2 during interfacial activation was more pronounced at higher negative charge densities of membranes. These findings identify a reciprocal relationship between the membrane surface properties, strength of membrane binding of PLA2, membrane-induced structural changes in PLA2, and the enzyme activation.

Full Text

The Full Text of this article is available as a PDF (832.5 KB).

Selected References

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

  1. Apitz-Castro R., Jain M. K., De Haas G. H. Origin of the latency phase during the action of phospholipase A2 on unmodified phosphatidylcholine vesicles. Biochim Biophys Acta. 1982 Jun 14;688(2):349–356. doi: 10.1016/0005-2736(82)90346-7. [DOI] [PubMed] [Google Scholar]
  2. Arni R. K., Ward R. J. Phospholipase A2--a structural review. Toxicon. 1996 Aug;34(8):827–841. doi: 10.1016/0041-0101(96)00036-0. [DOI] [PubMed] [Google Scholar]
  3. Arrondo J. L., Muga A., Castresana J., Goñi F. M. Quantitative studies of the structure of proteins in solution by Fourier-transform infrared spectroscopy. Prog Biophys Mol Biol. 1993;59(1):23–56. doi: 10.1016/0079-6107(93)90006-6. [DOI] [PubMed] [Google Scholar]
  4. Bayburt T., Yu B. Z., Lin H. K., Browning J., Jain M. K., Gelb M. H. Human nonpancreatic secreted phospholipase A2: interfacial parameters, substrate specificities, and competitive inhibitors. Biochemistry. 1993 Jan 19;32(2):573–582. doi: 10.1021/bi00053a024. [DOI] [PubMed] [Google Scholar]
  5. Bell J. D., Biltonen R. L. Molecular details of the activation of soluble phospholipase A2 on lipid bilayers. Comparison of computer simulations with experimental results. J Biol Chem. 1992 Jun 5;267(16):11046–11056. [PubMed] [Google Scholar]
  6. Bell J. D., Biltonen R. L. The temporal sequence of events in the activation of phospholipase A2 by lipid vesicles. Studies with the monomeric enzyme from Agkistrodon piscivorus piscivorus. J Biol Chem. 1989 Jul 25;264(21):12194–12200. [PubMed] [Google Scholar]
  7. Bell J. D., Burnside M., Owen J. A., Royall M. L., Baker M. L. Relationships between bilayer structure and phospholipase A2 activity: interactions among temperature, diacylglycerol, lysolecithin, palmitic acid, and dipalmitoylphosphatidylcholine. Biochemistry. 1996 Apr 16;35(15):4945–4955. doi: 10.1021/bi952274i. [DOI] [PubMed] [Google Scholar]
  8. Berg O. G., Rogers J., Yu B. Z., Yao J., Romsted L. S., Jain M. K. Thermodynamic and kinetic basis of interfacial activation: resolution of binding and allosteric effects on pancreatic phospholipase A2 at zwitterionic interfaces. Biochemistry. 1997 Nov 25;36(47):14512–14530. doi: 10.1021/bi970855x. [DOI] [PubMed] [Google Scholar]
  9. Berg O. G., Yu B. Z., Rogers J., Jain M. K. Interfacial catalysis by phospholipase A2: determination of the interfacial kinetic rate constants. Biochemistry. 1991 Jul 23;30(29):7283–7297. doi: 10.1021/bi00243a034. [DOI] [PubMed] [Google Scholar]
  10. Bradford M. M. A rapid and sensitive method for the quantitation of microgram quantities of protein utilizing the principle of protein-dye binding. Anal Biochem. 1976 May 7;72:248–254. doi: 10.1006/abio.1976.9999. [DOI] [PubMed] [Google Scholar]
  11. Brunie S., Bolin J., Gewirth D., Sigler P. B. The refined crystal structure of dimeric phospholipase A2 at 2.5 A. Access to a shielded catalytic center. J Biol Chem. 1985 Aug 15;260(17):9742–9749. [PubMed] [Google Scholar]
  12. Burack W. R., Biltonen R. L. Lipid bilayer heterogeneities and modulation of phospholipase A2 activity. Chem Phys Lipids. 1994 Sep 6;73(1-2):209–222. doi: 10.1016/0009-3084(94)90182-1. [DOI] [PubMed] [Google Scholar]
  13. Burack W. R., Dibble A. R., Allietta M. M., Biltonen R. L. Changes in vesicle morphology induced by lateral phase separation modulate phospholipase A2 activity. Biochemistry. 1997 Aug 26;36(34):10551–10557. doi: 10.1021/bi970509f. [DOI] [PubMed] [Google Scholar]
  14. Burack W. R., Gadd M. E., Biltonen R. L. Modulation of phospholipase A2: identification of an inactive membrane-bound state. Biochemistry. 1995 Nov 14;34(45):14819–14828. doi: 10.1021/bi00045a024. [DOI] [PubMed] [Google Scholar]
  15. Burack W. R., Yuan Q., Biltonen R. L. Role of lateral phase separation in the modulation of phospholipase A2 activity. Biochemistry. 1993 Jan 19;32(2):583–589. doi: 10.1021/bi00053a025. [DOI] [PubMed] [Google Scholar]
  16. Callisen T. H., Talmon Y. Direct imaging by cryo-TEM shows membrane break-up by phospholipase A2 enzymatic activity. Biochemistry. 1998 Aug 4;37(31):10987–10993. doi: 10.1021/bi980255d. [DOI] [PubMed] [Google Scholar]
  17. Cevc G., Seddon J. M., Hartung R., Eggert W. Phosphatidylcholine-fatty acid membranes. I. Effects of protonation, salt concentration, temperature and chain-length on the colloidal and phase properties of mixed vesicles, bilayers and nonlamellar structures. Biochim Biophys Acta. 1988 May 24;940(2):219–240. doi: 10.1016/0005-2736(88)90197-6. [DOI] [PubMed] [Google Scholar]
  18. Cha S. S., Lee D., Adams J., Kurdyla J. T., Jones C. S., Marshall L. A., Bolognese B., Abdel-Meguid S. S., Oh B. H. High-resolution X-ray crystallography reveals precise binding interactions between human nonpancreatic secreted phospholipase A2 and a highly potent inhibitor (FPL67047XX). J Med Chem. 1996 Sep 27;39(20):3878–3881. doi: 10.1021/jm960502g. [DOI] [PubMed] [Google Scholar]
  19. Chernyi V. V., Mirskii V. M., Sokolov V. S., Markin V. S. Elektrostaticheskii metod opredeleniia aktivnosti fosfolipazy A. Biokhimiia. 1990 Mar;55(3):445–450. [PubMed] [Google Scholar]
  20. Dennis E. A. Phospholipase A2 in eicosanoid generation. Am J Respir Crit Care Med. 2000 Feb;161(2 Pt 2):S32–S35. doi: 10.1164/ajrccm.161.supplement_1.ltta-7. [DOI] [PubMed] [Google Scholar]
  21. Dennis E. A. The growing phospholipase A2 superfamily of signal transduction enzymes. Trends Biochem Sci. 1997 Jan;22(1):1–2. doi: 10.1016/s0968-0004(96)20031-3. [DOI] [PubMed] [Google Scholar]
  22. Dwivedi A. M., Krimm S. Vibrational analysis of peptides, polypeptides, and proteins. XVIII. Conformational sensitivity of the alpha-helix spectrum: alpha I- and alpha II-poly(L-alanine). Biopolymers. 1984 May;23(5):923–943. doi: 10.1002/bip.360230509. [DOI] [PubMed] [Google Scholar]
  23. Forest C., Franckhauser S., Glorian M., Antras-Ferry J., Robin D., Robin P. Regulation of gene transcription by fatty acids, fibrates and prostaglandins: the phosphoenolpyruvate carboxykinase gene as a model. Prostaglandins Leukot Essent Fatty Acids. 1997 Jul;57(1):47–56. doi: 10.1016/s0952-3278(97)90492-0. [DOI] [PubMed] [Google Scholar]
  24. Fourcade O., Le Balle F., Fauvel J., Simon M. F., Chap H. Regulation of secretory type-II phospholipase A2 and of lysophosphatidic acid synthesis. Adv Enzyme Regul. 1998;38:99–107. doi: 10.1016/s0065-2571(97)00002-2. [DOI] [PubMed] [Google Scholar]
  25. Fringeli U. P., Apell H. J., Fringeli M., Läuger P. Polarized infrared absorption of Na+/K+-ATPase studied by attenuated total reflection spectroscopy. Biochim Biophys Acta. 1989 Sep 18;984(3):301–312. doi: 10.1016/0005-2736(89)90297-6. [DOI] [PubMed] [Google Scholar]
  26. Gelb M. H., Cho W., Wilton D. C. Interfacial binding of secreted phospholipases A(2): more than electrostatics and a major role for tryptophan. Curr Opin Struct Biol. 1999 Aug;9(4):428–432. doi: 10.1016/S0959-440X(99)80059-1. [DOI] [PubMed] [Google Scholar]
  27. Gelb M. H., Jain M. K., Hanel A. M., Berg O. G. Interfacial enzymology of glycerolipid hydrolases: lessons from secreted phospholipases A2. Annu Rev Biochem. 1995;64:653–688. doi: 10.1146/annurev.bi.64.070195.003253. [DOI] [PubMed] [Google Scholar]
  28. Gennero I., Xuereb J. M., Simon M. F., Girolami J. P., Bascands J. L., Chap H., Boneu B., Sié P. Effects of lysophosphatidic acid on proliferation and cytosolic Ca++ of human adult vascular smooth muscle cells in culture. Thromb Res. 1999 Jun 1;94(5):317–326. doi: 10.1016/s0049-3848(99)00004-3. [DOI] [PubMed] [Google Scholar]
  29. Ghomashchi F., Yu B. Z., Berg O., Jain M. K., Gelb M. H. Interfacial catalysis by phospholipase A2: substrate specificity in vesicles. Biochemistry. 1991 Jul 23;30(29):7318–7329. doi: 10.1021/bi00243a037. [DOI] [PubMed] [Google Scholar]
  30. Goodfriend T. L., Egan B. M. Nonesterified fatty acids in the pathogenesis of hypertension: theory and evidence. Prostaglandins Leukot Essent Fatty Acids. 1997 Jul;57(1):57–63. doi: 10.1016/s0952-3278(97)90493-2. [DOI] [PubMed] [Google Scholar]
  31. Han S. K., Yoon E. T., Scott D. L., Sigler P. B., Cho W. Structural aspects of interfacial adsorption. A crystallographic and site-directed mutagenesis study of the phospholipase A2 from the venom of Agkistrodon piscivorus piscivorus. J Biol Chem. 1997 Feb 7;272(6):3573–3582. [PubMed] [Google Scholar]
  32. Heinrikson R. L. Dissection and sequence analysis of phospholipases A2. Methods Enzymol. 1991;197:201–214. doi: 10.1016/0076-6879(91)97146-p. [DOI] [PubMed] [Google Scholar]
  33. Heller A., Koch T., Schmeck J., van Ackern K. Lipid mediators in inflammatory disorders. Drugs. 1998 Apr;55(4):487–496. doi: 10.2165/00003495-199855040-00001. [DOI] [PMC free article] [PubMed] [Google Scholar]
  34. Henshaw J. B., Olsen C. A., Farnbach A. R., Nielson K. H., Bell J. D. Definition of the specific roles of lysolecithin and palmitic acid in altering the susceptibility of dipalmitoylphosphatidylcholine bilayers to phospholipase A2. Biochemistry. 1998 Jul 28;37(30):10709–10721. doi: 10.1021/bi9728809. [DOI] [PubMed] [Google Scholar]
  35. Jackson J. R., Bolognese B., Mangar C. A., Hubbard W. C., Marshall L. A., Winkler J. D. The role of platelet activating factor and other lipid mediators in inflammatory angiogenesis. Biochim Biophys Acta. 1998 May 20;1392(1):145–152. doi: 10.1016/s0005-2760(98)00012-5. [DOI] [PubMed] [Google Scholar]
  36. Jackson M., Mantsch H. H. The use and misuse of FTIR spectroscopy in the determination of protein structure. Crit Rev Biochem Mol Biol. 1995;30(2):95–120. doi: 10.3109/10409239509085140. [DOI] [PubMed] [Google Scholar]
  37. Jain M. K., Berg O. G. The kinetics of interfacial catalysis by phospholipase A2 and regulation of interfacial activation: hopping versus scooting. Biochim Biophys Acta. 1989 Apr 3;1002(2):127–156. doi: 10.1016/0005-2760(89)90281-6. [DOI] [PubMed] [Google Scholar]
  38. Jain M. K., De Haas G. H. Activation of phospholipase A2 by freshly added lysophospholipids. Biochim Biophys Acta. 1983 Dec 21;736(2):157–162. doi: 10.1016/0005-2736(83)90279-1. [DOI] [PubMed] [Google Scholar]
  39. Jain M. K., Egmond M. R., Verheij H. M., Apitz-Castro R., Dijkman R., De Haas G. H. Interaction of phospholipase A2 and phospholipid bilayers. Biochim Biophys Acta. 1982 Jun 14;688(2):341–348. doi: 10.1016/0005-2736(82)90345-5. [DOI] [PubMed] [Google Scholar]
  40. Jain M. K., Maliwal B. P. Spectroscopic properties of the states of pig pancreatic phospholipase A2 at interfaces and their possible molecular origin. Biochemistry. 1993 Nov 9;32(44):11838–11846. doi: 10.1021/bi00095a012. [DOI] [PubMed] [Google Scholar]
  41. Jain M. K., Rogers J., Jahagirdar D. V., Marecek J. F., Ramirez F. Kinetics of interfacial catalysis by phospholipase A2 in intravesicle scooting mode, and heterofusion of anionic and zwitterionic vesicles. Biochim Biophys Acta. 1986 Sep 11;860(3):435–447. doi: 10.1016/0005-2736(86)90541-9. [DOI] [PubMed] [Google Scholar]
  42. Jain M. K., Yu B. Z., Kozubek A. Binding of phospholipase A2 to zwitterionic bilayers is promoted by lateral segregation of anionic amphiphiles. Biochim Biophys Acta. 1989 Mar 27;980(1):23–32. doi: 10.1016/0005-2736(89)90195-8. [DOI] [PubMed] [Google Scholar]
  43. Kume K., Shimizu T. Platelet-activating factor (PAF) induces growth stimulation, inhibition, and suppression of oncogenic transformation in NRK cells overexpressing the PAF receptor. J Biol Chem. 1997 Sep 5;272(36):22898–22904. doi: 10.1074/jbc.272.36.22898. [DOI] [PubMed] [Google Scholar]
  44. Liu F., Chong P. L. Evidence for a regulatory role of cholesterol superlattices in the hydrolytic activity of secretory phospholipase A2 in lipid membranes. Biochemistry. 1999 Mar 30;38(13):3867–3873. doi: 10.1021/bi982693q. [DOI] [PubMed] [Google Scholar]
  45. Maraganore J. M., Merutka G., Cho W., Welches W., Kézdy F. J., Heinrikson R. L. A new class of phospholipases A2 with lysine in place of aspartate 49. Functional consequences for calcium and substrate binding. J Biol Chem. 1984 Nov 25;259(22):13839–13843. [PubMed] [Google Scholar]
  46. Mezna M., Ahmad T., Chettibi S., Drainas D., Lawrence A. J. Zinc and barium inhibit the phospholipase A2 from Naja naja atra by different mechanisms. Biochem J. 1994 Jul 15;301(Pt 2):503–508. doi: 10.1042/bj3010503. [DOI] [PMC free article] [PubMed] [Google Scholar]
  47. Mukherjee A. B., Miele L., Pattabiraman N. Phospholipase A2 enzymes: regulation and physiological role. Biochem Pharmacol. 1994 Jul 5;48(1):1–10. doi: 10.1016/0006-2952(94)90216-x. [DOI] [PubMed] [Google Scholar]
  48. Murakami M., Shimbara S., Kambe T., Kuwata H., Winstead M. V., Tischfield J. A., Kudo I. The functions of five distinct mammalian phospholipase A2S in regulating arachidonic acid release. Type IIa and type V secretory phospholipase A2S are functionally redundant and act in concert with cytosolic phospholipase A2. J Biol Chem. 1998 Jun 5;273(23):14411–14423. doi: 10.1074/jbc.273.23.14411. [DOI] [PubMed] [Google Scholar]
  49. Peters A. R., Dekker N., van den Berg L., Boelens R., Kaptein R., Slotboom A. J., de Haas G. H. Conformational changes in phospholipase A2 upon binding to micellar interfaces in the absence and presence of competitive inhibitors. A 1H and 15N NMR study. Biochemistry. 1992 Oct 20;31(41):10024–10030. doi: 10.1021/bi00156a023. [DOI] [PubMed] [Google Scholar]
  50. Pieterson W. A., Vidal J. C., Volwerk J. J., de Haas G. H. Zymogen-catalyzed hydrolysis of monomeric substrates and the presence of a recognition site for lipid-water interfaces in phospholipase A2. Biochemistry. 1974 Mar 26;13(7):1455–1460. doi: 10.1021/bi00704a021. [DOI] [PubMed] [Google Scholar]
  51. Rogers J., Yu B. Z., Tsai M. D., Berg O. G., Jain M. K. Cationic residues 53 and 56 control the anion-induced interfacial k*cat activation of pancreatic phospholipase A2. Biochemistry. 1998 Jun 30;37(26):9549–9556. doi: 10.1021/bi972896z. [DOI] [PubMed] [Google Scholar]
  52. Schevitz R. W., Bach N. J., Carlson D. G., Chirgadze N. Y., Clawson D. K., Dillard R. D., Draheim S. E., Hartley L. W., Jones N. D., Mihelich E. D. Structure-based design of the first potent and selective inhibitor of human non-pancreatic secretory phospholipase A2. Nat Struct Biol. 1995 Jun;2(6):458–465. doi: 10.1038/nsb0695-458. [DOI] [PMC free article] [PubMed] [Google Scholar]
  53. Scott D. L., Mandel A. M., Sigler P. B., Honig B. The electrostatic basis for the interfacial binding of secretory phospholipases A2. Biophys J. 1994 Aug;67(2):493–504. doi: 10.1016/S0006-3495(94)80546-6. [DOI] [PMC free article] [PubMed] [Google Scholar]
  54. Scott D. L., Otwinowski Z., Gelb M. H., Sigler P. B. Crystal structure of bee-venom phospholipase A2 in a complex with a transition-state analogue. Science. 1990 Dec 14;250(4987):1563–1566. doi: 10.1126/science.2274788. [DOI] [PubMed] [Google Scholar]
  55. Scott D. L., Sigler P. B. Structure and catalytic mechanism of secretory phospholipases A2. Adv Protein Chem. 1994;45:53–88. doi: 10.1016/s0065-3233(08)60638-5. [DOI] [PubMed] [Google Scholar]
  56. Scott D. L., White S. P., Browning J. L., Rosa J. J., Gelb M. H., Sigler P. B. Structures of free and inhibited human secretory phospholipase A2 from inflammatory exudate. Science. 1991 Nov 15;254(5034):1007–1010. doi: 10.1126/science.1948070. [DOI] [PubMed] [Google Scholar]
  57. Scott D. L., White S. P., Otwinowski Z., Yuan W., Gelb M. H., Sigler P. B. Interfacial catalysis: the mechanism of phospholipase A2. Science. 1990 Dec 14;250(4987):1541–1546. doi: 10.1126/science.2274785. [DOI] [PMC free article] [PubMed] [Google Scholar]
  58. Sekar K., Eswaramoorthy S., Jain M. K., Sundaralingam M. Crystal structure of the complex of bovine pancreatic phospholipase A2 with the inhibitor 1-hexadecyl-3-(trifluoroethyl)-sn-glycero-2-phosphomethanol,. Biochemistry. 1997 Nov 18;36(46):14186–14191. doi: 10.1021/bi971370b. [DOI] [PubMed] [Google Scholar]
  59. Snitko Y., Koduri R. S., Han S. K., Othman R., Baker S. F., Molini B. J., Wilton D. C., Gelb M. H., Cho W. Mapping the interfacial binding surface of human secretory group IIa phospholipase A2. Biochemistry. 1997 Nov 25;36(47):14325–14333. doi: 10.1021/bi971200z. [DOI] [PubMed] [Google Scholar]
  60. Speijer H., Giesen P. L., Zwaal R. F., Hack C. E., Hermens W. T. Critical micelle concentrations and stirring are rate limiting in the loss of lipid mass during membrane degradation by phospholipase A2. Biophys J. 1996 May;70(5):2239–2247. doi: 10.1016/S0006-3495(96)79789-8. [DOI] [PMC free article] [PubMed] [Google Scholar]
  61. Tatulian S. A., Biltonen R. L., Tamm L. K. Structural changes in a secretory phospholipase A2 induced by membrane binding: a clue to interfacial activation? J Mol Biol. 1997 May 23;268(5):809–815. doi: 10.1006/jmbi.1997.1014. [DOI] [PubMed] [Google Scholar]
  62. Thunnissen M. M., Ab E., Kalk K. H., Drenth J., Dijkstra B. W., Kuipers O. P., Dijkman R., de Haas G. H., Verheij H. M. X-ray structure of phospholipase A2 complexed with a substrate-derived inhibitor. Nature. 1990 Oct 18;347(6294):689–691. doi: 10.1038/347689a0. [DOI] [PubMed] [Google Scholar]
  63. Tischfield J. A. A reassessment of the low molecular weight phospholipase A2 gene family in mammals. J Biol Chem. 1997 Jul 11;272(28):17247–17250. doi: 10.1074/jbc.272.28.17247. [DOI] [PubMed] [Google Scholar]
  64. Tomoo K., Ohishi H., Ishida T., Inoue M., Ikeda K., Sumiya S., Kitamura K. X-ray crystal structure and molecular dynamics simulation of bovine pancreas phospholipase A2-n-dodecylphosphorylcholine complex. Proteins. 1994 Aug;19(4):330–339. doi: 10.1002/prot.340190408. [DOI] [PubMed] [Google Scholar]
  65. Venyaminov SYu, Kalnin N. N. Quantitative IR spectrophotometry of peptide compounds in water (H2O) solutions. I. Spectral parameters of amino acid residue absorption bands. Biopolymers. 1990;30(13-14):1243–1257. doi: 10.1002/bip.360301309. [DOI] [PubMed] [Google Scholar]
  66. Verger R. Interfacial enzyme kinetics of lipolysis. Annu Rev Biophys Bioeng. 1976;5:77–117. doi: 10.1146/annurev.bb.05.060176.000453. [DOI] [PubMed] [Google Scholar]
  67. Volwerk J. J., Jost P. C., de Haas G. H., Griffith O. H. Activation of porcine pancreatic phospholipase A2 by the presence of negative charges at the lipid-water interface. Biochemistry. 1986 Apr 8;25(7):1726–1733. doi: 10.1021/bi00355a042. [DOI] [PubMed] [Google Scholar]
  68. Welches W., Reardon I., Heinrikson R. L. An examination of structural interactions presumed to be of importance in the stabilization of phospholipase A2 dimers based upon comparative protein sequence analysis of a monomeric and dimeric enzyme from the venom of Agkistrodon p. piscivorus. J Protein Chem. 1993 Apr;12(2):187–193. doi: 10.1007/BF01026040. [DOI] [PubMed] [Google Scholar]
  69. White S. P., Scott D. L., Otwinowski Z., Gelb M. H., Sigler P. B. Crystal structure of cobra-venom phospholipase A2 in a complex with a transition-state analogue. Science. 1990 Dec 14;250(4987):1560–1563. doi: 10.1126/science.2274787. [DOI] [PubMed] [Google Scholar]
  70. Yu B. Z., Rogers J., Nicol G. R., Theopold K. H., Seshadri K., Vishweshwara S., Jain M. K. Catalytic significance of the specificity of divalent cations as KS* and kcat* cofactors for secreted phospholipase A2. Biochemistry. 1998 Sep 8;37(36):12576–12587. doi: 10.1021/bi9728607. [DOI] [PubMed] [Google Scholar]
  71. Yu B. Z., Rogers J., Tsai M. D., Pidgeon C., Jain M. K. Contributions of residues of pancreatic phospholipase A2 to interfacial binding, catalysis, and activation. Biochemistry. 1999 Apr 13;38(15):4875–4884. doi: 10.1021/bi982215f. [DOI] [PubMed] [Google Scholar]
  72. van den Berg B., Tessari M., Boelens R., Dijkman R., de Haas G. H., Kaptein R., Verheij H. M. NMR structures of phospholipase A2 reveal conformational changes during interfacial activation. Nat Struct Biol. 1995 May;2(5):402–406. doi: 10.1038/nsb0595-402. [DOI] [PubMed] [Google Scholar]

Articles from Biophysical Journal are provided here courtesy of The Biophysical Society

RESOURCES