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. 1996 May;5(5):836–851. doi: 10.1002/pro.5560050505

Structural investigation of the alpha-1-antichymotrypsin: prostate-specific antigen complex by comparative model building.

B O Villoutreix 1, H Lilja 1, K Pettersson 1, T Lövgren 1, O Teleman 1
PMCID: PMC2143410  PMID: 8732755

Abstract

Prostate-specific antigen (PSA), produced by prostate cells, provides an excellent serum marker for prostate cancer. It belongs to the human kallikrein family of enzymes, a second prostate-derived member of which is human glandular kallikrein-1 (hK2). Active PSA and hK2 are both 237-residue kallikrein-like proteases, based on sequence homology. An hK2 model structure based on the serine protease fold is presented and compared to PSA and six other serine proteases in order to analyze in depth the role of the surface-accessible loops surrounding the active site. The results show that PSA and hK2 share extensive structural similarity and that most amino acid replacements are centered on the loops surrounding the active site. Furthermore, the electrostatic potential surfaces are very similar for PSA and hK2. PSA interacts with at least two serine protease inhibitors (serpins): alpha-1-antichymotrypsin (ACT) and protein C inhibitor (PCI). Three-dimensional model structures of the uncleaved ACT molecule were developed based upon the recent X-ray structure of uncleaved antithrombin. The serpin was docked both to PSA and hK2. Amino acid replacements and electrostatic complementarities indicate that the overall orientation of the proteins in these complexes is reasonable. In order to investigate PSA's heparin interaction sites, electrostatic computations were carried out on PSA, hK2, protein C, ACT, and PCI. Two heparin binding sites are suggested on the PSA surface and could explain the enhanced complex formation between PSA and PCI, while inhibiting the formation of the ACT-PSA complex, PSA, hK2, and their preliminary complexes with ACT should facilitate the understanding and prediction of structural and functional properties for these important proteins also with respect to prostate diseases.

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Selected References

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  1. Akiyama K., Nakamura T., Iwanaga S., Hara M. The chymotrypsin-like activity of human prostate-specific antigen, gamma-seminoprotein. FEBS Lett. 1987 Dec 10;225(1-2):168–172. doi: 10.1016/0014-5793(87)81151-1. [DOI] [PubMed] [Google Scholar]
  2. Bartunik H. D., Summers L. J., Bartsch H. H. Crystal structure of bovine beta-trypsin at 1.5 A resolution in a crystal form with low molecular packing density. Active site geometry, ion pairs and solvent structure. J Mol Biol. 1989 Dec 20;210(4):813–828. doi: 10.1016/0022-2836(89)90110-1. [DOI] [PubMed] [Google Scholar]
  3. Bashford D., Gerwert K. Electrostatic calculations of the pKa values of ionizable groups in bacteriorhodopsin. J Mol Biol. 1992 Mar 20;224(2):473–486. doi: 10.1016/0022-2836(92)91009-e. [DOI] [PubMed] [Google Scholar]
  4. Baumann U., Huber R., Bode W., Grosse D., Lesjak M., Laurell C. B. Crystal structure of cleaved human alpha 1-antichymotrypsin at 2.7 A resolution and its comparison with other serpins. J Mol Biol. 1991 Apr 5;218(3):595–606. doi: 10.1016/0022-2836(91)90704-a. [DOI] [PubMed] [Google Scholar]
  5. Bernstein F. C., Koetzle T. F., Williams G. J., Meyer E. F., Jr, Brice M. D., Rodgers J. R., Kennard O., Shimanouchi T., Tasumi M. The Protein Data Bank: a computer-based archival file for macromolecular structures. J Mol Biol. 1977 May 25;112(3):535–542. doi: 10.1016/s0022-2836(77)80200-3. [DOI] [PubMed] [Google Scholar]
  6. Blundell T. L., Sibanda B. L., Sternberg M. J., Thornton J. M. Knowledge-based prediction of protein structures and the design of novel molecules. 1987 Mar 26-Apr 1Nature. 326(6111):347–352. doi: 10.1038/326347a0. [DOI] [PubMed] [Google Scholar]
  7. Bode W., Huber R. Natural protein proteinase inhibitors and their interaction with proteinases. Eur J Biochem. 1992 Mar 1;204(2):433–451. doi: 10.1111/j.1432-1033.1992.tb16654.x. [DOI] [PubMed] [Google Scholar]
  8. 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]
  9. Bode W. The transition of bovine trypsinogen to a trypsin-like state upon strong ligand binding. II. The binding of the pancreatic trypsin inhibitor and of isoleucine-valine and of sequentially related peptides to trypsinogen and to p-guanidinobenzoate-trypsinogen. J Mol Biol. 1979 Feb 5;127(4):357–374. doi: 10.1016/0022-2836(79)90227-4. [DOI] [PubMed] [Google Scholar]
  10. Bode W., Turk D., Karshikov A. The refined 1.9-A X-ray crystal structure of D-Phe-Pro-Arg chloromethylketone-inhibited human alpha-thrombin: structure analysis, overall structure, electrostatic properties, detailed active-site geometry, and structure-function relationships. Protein Sci. 1992 Apr;1(4):426–471. doi: 10.1002/pro.5560010402. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Bridon D. P., Dowell B. L. Structural comparison of prostate-specific antigen and human glandular kallikrein using molecular modeling. Urology. 1995 May;45(5):801–806. doi: 10.1016/S0090-4295(99)80087-9. [DOI] [PubMed] [Google Scholar]
  12. Brillard-Bourdet M., Moreau T., Gauthier F. Substrate specificity of tissue kallikreins: importance of an extended interaction site. Biochim Biophys Acta. 1995 Jan 5;1246(1):47–52. doi: 10.1016/0167-4838(94)00179-k. [DOI] [PubMed] [Google Scholar]
  13. Bélanger A., van Halbeek H., Graves H. C., Grandbois K., Stamey T. A., Huang L., Poppe I., Labrie F. Molecular mass and carbohydrate structure of prostate specific antigen: studies for establishment of an international PSA standard. Prostate. 1995 Oct;27(4):187–197. doi: 10.1002/pros.2990270403. [DOI] [PubMed] [Google Scholar]
  14. Carrell R. W., Stein P. E., Fermi G., Wardell M. R. Biological implications of a 3 A structure of dimeric antithrombin. Structure. 1994 Apr 15;2(4):257–270. doi: 10.1016/s0969-2126(00)00028-9. [DOI] [PubMed] [Google Scholar]
  15. Chen Z., Bode W. Refined 2.5 A X-ray crystal structure of the complex formed by porcine kallikrein A and the bovine pancreatic trypsin inhibitor. Crystallization, Patterson search, structure determination, refinement, structure and comparison with its components and with the bovine trypsin-pancreatic trypsin inhibitor complex. J Mol Biol. 1983 Feb 25;164(2):283–311. doi: 10.1016/0022-2836(83)90078-5. [DOI] [PubMed] [Google Scholar]
  16. Christensson A., Björk T., Nilsson O., Dahlén U., Matikainen M. T., Cockett A. T., Abrahamsson P. A., Lilja H. Serum prostate specific antigen complexed to alpha 1-antichymotrypsin as an indicator of prostate cancer. J Urol. 1993 Jul;150(1):100–105. doi: 10.1016/s0022-5347(17)35408-3. [DOI] [PubMed] [Google Scholar]
  17. Christensson A., Laurell C. B., Lilja H. Enzymatic activity of prostate-specific antigen and its reactions with extracellular serine proteinase inhibitors. Eur J Biochem. 1990 Dec 27;194(3):755–763. doi: 10.1111/j.1432-1033.1990.tb19466.x. [DOI] [PubMed] [Google Scholar]
  18. Christensson A., Lilja H. Complex formation between protein C inhibitor and prostate-specific antigen in vitro and in human semen. Eur J Biochem. 1994 Feb 15;220(1):45–53. doi: 10.1111/j.1432-1033.1994.tb18597.x. [DOI] [PubMed] [Google Scholar]
  19. Clements J., Mukhtar A. Glandular kallikreins and prostate-specific antigen are expressed in the human endometrium. J Clin Endocrinol Metab. 1994 Jun;78(6):1536–1539. doi: 10.1210/jcem.78.6.7515392. [DOI] [PubMed] [Google Scholar]
  20. Cooper S. T., Whinna H. C., Jackson T. P., Boyd J. M., Church F. C. Intermolecular interactions between protein C inhibitor and coagulation proteases. Biochemistry. 1995 Oct 10;34(40):12991–12997. doi: 10.1021/bi00040a009. [DOI] [PubMed] [Google Scholar]
  21. España F., Gilabert J., Estellés A., Romeu A., Aznar J., Cabo A. Functionally active protein C inhibitor/plasminogen activator inhibitor-3 (PCI/PAI-3) is secreted in seminal vesicles, occurs at high concentrations in human seminal plasma and complexes with prostate-specific antigen. Thromb Res. 1991 Nov 1;64(3):309–320. doi: 10.1016/0049-3848(91)90002-e. [DOI] [PubMed] [Google Scholar]
  22. España F., Sanchez-Cuenca J., Vera C. D., Estelles A., Gilabert J. A quantitative ELISA for the measurement of complexes of prostate-specific antigen with protein C inhibitor when using a purified standard. J Lab Clin Med. 1993 Dec;122(6):711–719. [PubMed] [Google Scholar]
  23. Fernández J. A., Villoutreix B. O., Hackeng T. M., Griffin J. H., Bouma B. N. Analysis of protein S C4b-binding protein interactions by homology modeling and inhibitory antibodies. Biochemistry. 1994 Sep 20;33(37):11073–11078. doi: 10.1021/bi00203a003. [DOI] [PubMed] [Google Scholar]
  24. Fisher C. L., Greengard J. S., Griffin J. H. Models of the serine protease domain of the human antithrombotic plasma factor activated protein C and its zymogen. Protein Sci. 1994 Apr;3(4):588–599. doi: 10.1002/pro.5560030407. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. Frigerio F., Coda A., Pugliese L., Lionetti C., Menegatti E., Amiconi G., Schnebli H. P., Ascenzi P., Bolognesi M. Crystal and molecular structure of the bovine alpha-chymotrypsin-eglin c complex at 2.0 A resolution. J Mol Biol. 1992 May 5;225(1):107–123. doi: 10.1016/0022-2836(92)91029-o. [DOI] [PubMed] [Google Scholar]
  26. 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]
  27. Furie B., Bing D. H., Feldmann R. J., Robison D. J., Burnier J. P., Furie B. C. Computer-generated models of blood coagulation factor Xa, factor IXa, and thrombin based upon structural homology with other serine proteases. J Biol Chem. 1982 Apr 10;257(7):3875–3882. [PubMed] [Google Scholar]
  28. Greengard J. S., Fisher C. L., Villoutreix B., Griffin J. H. Structural basis for type I and type II deficiencies of antithrombotic plasma protein C: patterns revealed by three-dimensional molecular modelling of mutations of the protease domain. Proteins. 1994 Apr;18(4):367–380. doi: 10.1002/prot.340180407. [DOI] [PubMed] [Google Scholar]
  29. 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]
  30. Greer J. Model of a specific interaction. Salt-bridges form between prothrombin and its activating enzyme blood clotting factor Xa. J Mol Biol. 1981 Dec 25;153(4):1043–1053. doi: 10.1016/0022-2836(81)90466-6. [DOI] [PubMed] [Google Scholar]
  31. Hagler A. T., Lifson S. Energy functions for peptides and proteins. II. The amide hydrogen bond and calculation of amide crystal properties. J Am Chem Soc. 1974 Aug 21;96(17):5327–5335. doi: 10.1021/ja00824a005. [DOI] [PubMed] [Google Scholar]
  32. Harvey S. C. Treatment of electrostatic effects in macromolecular modeling. Proteins. 1989;5(1):78–92. doi: 10.1002/prot.340050109. [DOI] [PubMed] [Google Scholar]
  33. 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]
  34. Huber R., Carrell R. W. Implications of the three-dimensional structure of alpha 1-antitrypsin for structure and function of serpins. Biochemistry. 1989 Nov 14;28(23):8951–8966. doi: 10.1021/bi00449a001. [DOI] [PubMed] [Google Scholar]
  35. Jordan R. E., Oosta G. M., Gardner W. T., Rosenberg R. D. The kinetics of hemostatic enzyme-antithrombin interactions in the presence of low molecular weight heparin. J Biol Chem. 1980 Nov 10;255(21):10081–10090. [PubMed] [Google Scholar]
  36. Karshikov A., Bode W., Tulinsky A., Stone S. R. Electrostatic interactions in the association of proteins: an analysis of the thrombin-hirudin complex. Protein Sci. 1992 Jun;1(6):727–735. doi: 10.1002/pro.5560010605. [DOI] [PMC free article] [PubMed] [Google Scholar]
  37. Kuhn L. A., Griffin J. H., Fisher C. L., Greengard J. S., Bouma B. N., España F., Tainer J. A. Elucidating the structural chemistry of glycosaminoglycan recognition by protein C inhibitor. Proc Natl Acad Sci U S A. 1990 Nov;87(21):8506–8510. doi: 10.1073/pnas.87.21.8506. [DOI] [PMC free article] [PubMed] [Google Scholar]
  38. Le Bonniec B. F., Guinto E. R., Stone S. R. Identification of thrombin residues that modulate its interactions with antithrombin III and alpha 1-antitrypsin. Biochemistry. 1995 Sep 26;34(38):12241–12248. doi: 10.1021/bi00038a019. [DOI] [PubMed] [Google Scholar]
  39. Lee B., Richards F. M. The interpretation of protein structures: estimation of static accessibility. J Mol Biol. 1971 Feb 14;55(3):379–400. doi: 10.1016/0022-2836(71)90324-x. [DOI] [PubMed] [Google Scholar]
  40. Leinonen J., Lövgren T., Vornanen T., Stenman U. H. Double-label time-resolved immunofluorometric assay of prostate-specific antigen and of its complex with alpha 1-antichymotrypsin. Clin Chem. 1993 Oct;39(10):2098–2103. [PubMed] [Google Scholar]
  41. Lilja H., Abrahamsson P. A., Lundwall A. Semenogelin, the predominant protein in human semen. Primary structure and identification of closely related proteins in the male accessory sex glands and on the spermatozoa. J Biol Chem. 1989 Jan 25;264(3):1894–1900. [PubMed] [Google Scholar]
  42. Lilja H., Christensson A., Dahlén U., Matikainen M. T., Nilsson O., Pettersson K., Lövgren T. Prostate-specific antigen in serum occurs predominantly in complex with alpha 1-antichymotrypsin. Clin Chem. 1991 Sep;37(9):1618–1625. [PubMed] [Google Scholar]
  43. Loebermann H., Tokuoka R., Deisenhofer J., Huber R. Human alpha 1-proteinase inhibitor. Crystal structure analysis of two crystal modifications, molecular model and preliminary analysis of the implications for function. J Mol Biol. 1984 Aug 15;177(3):531–557. [PubMed] [Google Scholar]
  44. Lövgren J., Piironen T., Overmo C., Dowell B., Karp M., Pettersson K., Lilja H., Lundwall A. Production of recombinant PSA and HK2 and analysis of their immunologic cross-reactivity. Biochem Biophys Res Commun. 1995 Aug 24;213(3):888–895. doi: 10.1006/bbrc.1995.2212. [DOI] [PubMed] [Google Scholar]
  45. Madison E. L., Goldsmith E. J., Gerard R. D., Gething M. J., Sambrook J. F. Serpin-resistant mutants of human tissue-type plasminogen activator. Nature. 1989 Jun 29;339(6227):721–724. doi: 10.1038/339721a0. [DOI] [PubMed] [Google Scholar]
  46. Madison E. L., Goldsmith E. J., Gething M. J., Sambrook J. F., Gerard R. D. Restoration of serine protease-inhibitor interaction by protein engineering. J Biol Chem. 1990 Dec 15;265(35):21423–21426. [PubMed] [Google Scholar]
  47. Perona J. J., Craik C. S. Structural basis of substrate specificity in the serine proteases. Protein Sci. 1995 Mar;4(3):337–360. doi: 10.1002/pro.5560040301. [DOI] [PMC free article] [PubMed] [Google Scholar]
  48. Ponder J. W., Richards F. M. Tertiary templates for proteins. Use of packing criteria in the enumeration of allowed sequences for different structural classes. J Mol Biol. 1987 Feb 20;193(4):775–791. doi: 10.1016/0022-2836(87)90358-5. [DOI] [PubMed] [Google Scholar]
  49. Radtke K. P., Fernández J. A., Villoutreix B. O., Greengard J. S., Griffin J. H. Characterization of a cDNA for rhesus monkey protein C inhibitor--evidence for N-terminal involvement in heparin stimulation. Thromb Haemost. 1995 Oct;74(4):1079–1087. [PubMed] [Google Scholar]
  50. Riegman P. H., Vlietstra R. J., Suurmeijer L., Cleutjens C. B., Trapman J. Characterization of the human kallikrein locus. Genomics. 1992 Sep;14(1):6–11. doi: 10.1016/s0888-7543(05)80275-7. [DOI] [PubMed] [Google Scholar]
  51. Schaller J., Akiyama K., Tsuda R., Hara M., Marti T., Rickli E. E. Isolation, characterization and amino-acid sequence of gamma-seminoprotein, a glycoprotein from human seminal plasma. Eur J Biochem. 1987 Dec 30;170(1-2):111–120. doi: 10.1111/j.1432-1033.1987.tb13674.x. [DOI] [PubMed] [Google Scholar]
  52. 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]
  53. Schedlich L. J., Bennetts B. H., Morris B. J. Primary structure of a human glandular kallikrein gene. DNA. 1987 Oct;6(5):429–437. doi: 10.1089/dna.1987.6.429. [DOI] [PubMed] [Google Scholar]
  54. Schreuder H. A., de Boer B., Dijkema R., Mulders J., Theunissen H. J., Grootenhuis P. D., Hol W. G. The intact and cleaved human antithrombin III complex as a model for serpin-proteinase interactions. Nat Struct Biol. 1994 Jan;1(1):48–54. doi: 10.1038/nsb0194-48. [DOI] [PubMed] [Google Scholar]
  55. Sharp K. A., Honig B. Electrostatic interactions in macromolecules: theory and applications. Annu Rev Biophys Biophys Chem. 1990;19:301–332. doi: 10.1146/annurev.bb.19.060190.001505. [DOI] [PubMed] [Google Scholar]
  56. Sheehan J. P., Sadler J. E. Molecular mapping of the heparin-binding exosite of thrombin. Proc Natl Acad Sci U S A. 1994 Jun 7;91(12):5518–5522. doi: 10.1073/pnas.91.12.5518. [DOI] [PMC free article] [PubMed] [Google Scholar]
  57. Shenkin P. S., Yarmush D. L., Fine R. M., Wang H. J., Levinthal C. Predicting antibody hypervariable loop conformation. I. Ensembles of random conformations for ringlike structures. Biopolymers. 1987 Dec;26(12):2053–2085. doi: 10.1002/bip.360261207. [DOI] [PubMed] [Google Scholar]
  58. Shirk R. A., Elisen M. G., Meijers J. C., Church F. C. Role of the H helix in heparin binding to protein C inhibitor. J Biol Chem. 1994 Nov 18;269(46):28690–28695. [PubMed] [Google Scholar]
  59. Stein P. E., Leslie A. G., Finch J. T., Carrell R. W. Crystal structure of uncleaved ovalbumin at 1.95 A resolution. J Mol Biol. 1991 Oct 5;221(3):941–959. doi: 10.1016/0022-2836(91)80185-w. [DOI] [PubMed] [Google Scholar]
  60. Stein P. E., Leslie A. G., Finch J. T., Turnell W. G., McLaughlin P. J., Carrell R. W. Crystal structure of ovalbumin as a model for the reactive centre of serpins. Nature. 1990 Sep 6;347(6288):99–102. doi: 10.1038/347099a0. [DOI] [PubMed] [Google Scholar]
  61. Stenman U. H., Leinonen J., Alfthan H., Rannikko S., Tuhkanen K., Alfthan O. A complex between prostate-specific antigen and alpha 1-antichymotrypsin is the major form of prostate-specific antigen in serum of patients with prostatic cancer: assay of the complex improves clinical sensitivity for cancer. Cancer Res. 1991 Jan 1;51(1):222–226. [PubMed] [Google Scholar]
  62. Sunnerhagen M., Forsén S., Hoffrén A. M., Drakenberg T., Teleman O., Stenflo J. Structure of the Ca(2+)-free Gla domain sheds light on membrane binding of blood coagulation proteins. Nat Struct Biol. 1995 Jun;2(6):504–509. doi: 10.1038/nsb0695-504. [DOI] [PubMed] [Google Scholar]
  63. Suzuki K., Nishioka J., Hashimoto S. Protein C inhibitor. Purification from human plasma and characterization. J Biol Chem. 1983 Jan 10;258(1):163–168. [PubMed] [Google Scholar]
  64. Vihinen M. Modeling of prostate specific antigen and human glandular kallikrein structures. Biochem Biophys Res Commun. 1994 Nov 15;204(3):1251–1256. doi: 10.1006/bbrc.1994.2597. [DOI] [PubMed] [Google Scholar]
  65. Villoutreix B. O., Getzoff E. D., Griffin J. H. A structural model for the prostate disease marker, human prostate-specific antigen. Protein Sci. 1994 Nov;3(11):2033–2044. doi: 10.1002/pro.5560031116. [DOI] [PMC free article] [PubMed] [Google Scholar]
  66. Warshel A., Aqvist J. Electrostatic energy and macromolecular function. Annu Rev Biophys Biophys Chem. 1991;20:267–298. doi: 10.1146/annurev.bb.20.060191.001411. [DOI] [PubMed] [Google Scholar]
  67. Watt K. W., Lee P. J., M'Timkulu T., Chan W. P., Loor R. Human prostate-specific antigen: structural and functional similarity with serine proteases. Proc Natl Acad Sci U S A. 1986 May;83(10):3166–3170. doi: 10.1073/pnas.83.10.3166. [DOI] [PMC free article] [PubMed] [Google Scholar]
  68. Wei A., Rubin H., Cooperman B. S., Christianson D. W. Crystal structure of an uncleaved serpin reveals the conformation of an inhibitory reactive loop. Nat Struct Biol. 1994 Apr;1(4):251–258. doi: 10.1038/nsb0494-251. [DOI] [PubMed] [Google Scholar]
  69. Wright H. T., Qian H. X., Huber R. Crystal structure of plakalbumin, a proteolytically nicked form of ovalbumin. Its relationship to the structure of cleaved alpha-1-proteinase inhibitor. J Mol Biol. 1990 Jun 5;213(3):513–528. doi: 10.1016/s0022-2836(05)80212-8. [DOI] [PubMed] [Google Scholar]
  70. Young C. Y., Andrews P. E., Montgomery B. T., Tindall D. J. Tissue-specific and hormonal regulation of human prostate-specific glandular kallikrein. Biochemistry. 1992 Jan 28;31(3):818–824. doi: 10.1021/bi00118a026. [DOI] [PubMed] [Google Scholar]
  71. Yu H., Diamandis E. P. Prostate-specific antigen in milk of lactating women. Clin Chem. 1995 Jan;41(1):54–58. [PubMed] [Google Scholar]

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