Structure-based drug design strategies for inhibition of aspartic proteinases

Aspartic Acid Proteases as Therapeutic Targets

Volumn 45, Issue , 2011, Pages 71-105

  Cooper, Jon B ^a  

^a ROYAL FREE AND UNIVERSITY COLLEGE MEDICAL SCHOOL   (United Kingdom)

Author keywords

Amyloid; Angiotensin; Aspartic proteinase; Cathepsin; Deoxyribonucleic acid; Glycol

Indexed keywords

EID: 84884869431     PISSN: None     EISSN: None     Source Type: Book    
DOI: 10.1002/9783527630943.ch4     Document Type: Chapter

References (92)

1. Ondetti, M.A. and Cushman, D.W. (1982) Enzymes of the renin-angiotensin system and their inhibitors. Annual Review of Biochemistry, 51, 283-308.
2. Piot, P., Bartos, M.,Ghys, P.D.,Walker, N., and Schwartlander, B. (2001) The global impact of HIV/AIDS. Nature, 410, 968. -973.
3. Tomasselli, A.G. and Heinrikson, R.L. (2000) Targeting the HIV-protease in AIDS therapy: a current clinical perspective. Biochimica et Biophysica Acta, 1477. , 189-214.
4. Fassbender, K., Masters, C., and Beyreuther, K. (2001) Alzheimer's disease: molecular concepts and therapeutic targets. Die Naturwissenschaften, 88, 261-267.
5. Serpell, L.C., Blake, C.C.F., and Fraser, P.E. (2000) Molecular structure of a fibrillar Alzheimer's Ab fragment. The Biochemical Journal, 39, 13269-13275.
6. Haass, C. (2004) Take five: BACE and the c-secretase quartet conduct Alzheimer's amyloid b-peptide generation. The EMBO Journal, 23, 483-488.
7. Hong, L., Koelsch, G., Lin, X.L.,Wu, S.L., Terzyan, S., Ghosh, A.K., Zhang, X.C., and Tang, J. (2000) Structure of the protease domain of memapsin 2 (b-secretase) complexed with inhibitor. Science, 290, 150-153.
8. Pichova, I., Pavlikova, L., Dostal, J., Dolejši, E., Hruškova-Heidingsfeldova, O., Weber, J., Ruml, T., and Soucek, M. (2001) Secreted aspartic proteases of Candida albicans, Candida tropicalis, Candida parapsilosis and Candida lusitaniae. Inhibition with peptidomimetic inhibitors. European Journal of Biochemistry, 268, 2669-2677.
9. Fujinaga, M., Cherney, M.M., Tarasova, N.I., Bartlett, P.A.,Hanson, J.E., and James, M.N.G. (2000) Structural study of the complex between human pepsin and a phosphorus-containing peptidic transition-state analog. Acta Crystallographica, D56, 272-279.
10. Liaudet-Coopman, E., Beaujouin, M., Derocq, D.,Garcia, M., Glondu-Lassis, M., Laurent-Matha, V., Prebois, C., Rochefort, H., and Vignon, F. (2006) Cathepsin D: newly discovered functions of a long-standing aspartic protease in cancer and apoptosis. Cancer Letters, 237, 167-179.
11. Vetvicka, V., Vetvickova, J., and Fusek, M. (1999) Anti-human procathepsin D activation peptide antibodies inhibit breast cancer development. Breast Cancer Research and Treatment, 57, 261-269.
12. Fusek, M. and Vetvicka, V. (1994) Mitogenic function of human procathepsin-D: the role of the propeptide. The Biochemical Journal, 303, 775-780.
13. Silva, A.M., Lee, A.Y., Gulnik, S.V., Majer, P., Collins, J., Bhat, T.N., Collins, P.J., Cachau, R.E., Luker, K.E., Gluzman, I.Y., Francis, S.E., Oksman, A., Goldberg, D.E., and Erickson, J.E. (1996) Structure and inhibition of plasmepsin II, a hemoglobin-degrading enzyme from Plasmodium falciparum. Proceedings of the National Academy of Sciences of the United States of America, 93, 10034-10039.
14. Carroll, C.D., Patel, H., Johnson, T.O., Guo, T., Orlowski, M., He, Z.M., Cavallaro, C.L., Guo, J., Oksman, A., Gluzman, I.Y., Connelly, J., Chelsky, D., Goldberg, D.E., and Dolle, E. (1998) Identification of potent inhibitors of Plasmodium falciparum plasmepsin II from an encoded statine combinatorial library. Bioorganic & Medicinal Chemistry Letters, 8, 2315-2320.
15. Blundell, T.L., Cooper, J., Foundling, S.I., Jones, D.M., Atrash, B., and Szelke, M. (1987) On the rational design of renin inhibitors: X-ray studies of aspartic proteinases complexed with transition state analogues. Biochemistry, 26, 5585. -5590.
16. Pearl, L.H. and Blundell, T.L. (1994) The active sites of aspartic proteinases. FEBS Letters, 174, 96-101.
17. Dhanaraj, V., Dealwis, C., Frazao, C., Badasso, M., Sibanda, B.L., Tickle, I.J., Cooper, J.B., Driessen, H.P.C., Newman, M., Aguilar, C., Wood, S.P., Blundell, T.L., Hobart, P.M., Geoghegan, K.F., Ammirati, M.J., Danley, D.E., OConnor, B.A., and Hoover, D.J. (1992) X-ray analyses of peptide-inhibitor complexes define the structural basis of specificity for human and mouse renins. Nature, 357, 466-472.
18. Sibanda, B.L., Blundell,T.L., Hobart, P.M., Fogliano, M., Bindra, J.S., Dominy, B.W., and Chirgwin, J.M. (1984) Computer graphics modelling of humanrenin. FEBS Letters, 174, 102-111.
19. Skeggs, L.T., Dover, F.E., Levine, M., Lentz, K.E., and Kahn, J.R. (1980) The Renin-Angiotensin System (eds J.A. Johnson and R.R. Anderson), Plenum Press, New York, pp. 1-27.
20. Bone, R., Silen, J.L., and Agard, D.A. (1989) Structural plasticity broadens the specificity of an engineered protease. Nature, 339, 191-195.
21. Haber, E. and Burton, J. (1979) Inhibitors of renin and their utility in physiologic studies. Federation Proceedings, 38, 2768. -2773.
22. Cooper, J.B. and Bailey, D.A. (1994) Structural comparison of 21 inhibitor complexes of the aspartic proteinase from Endothia parasitica. Protein Science, 3, 2129. -2143.
23. Foundling, S.I., Cooper, J., Watson, F.E., Cleasby, A., Pearl, L.H., Sibanda, B.L., Hemmings, A.,Wood, S.P., Blundell, T.L., Valler, M.J., Norey, C.G., Kay, J., Boger, J., Dunn, B.M., Leckie, B.J., Jones, D.M., Atrash, B., Hallett, A., and Szelke, M. (1987) High resolution X-ray analyses of renin inhibitor-aspartic proteinase complexes. Nature, 327, 349. -352.
24. Luly, J.R., Bolis, G., Bamaung, N., Soderquist, J., Dellaria, J.F., Stein, H., Cohen, J., Thomas, J.P., Greer, J., and Plattner, J.J. (1988) New inhibitors of human renin that contain novel replacements. Examination of the P1 site. Journal of Medicinal Chemistry, 31, 532. -539.
25. Hofmann, T. and Fink, A.L. (1984) Cryoenzymology of penicillopepsin. Biochemistry, 23, 5249-5256.
26. Szelke, M., Leckie, B., Hallett, A., Jones, D.M., Sueiras-Diaz, J., Atrash, B., and Lever, A.F. (1982) Potent new inhibitors of human renin. Nature, 299, 555. -557.
27. Boger, J. (1985) Renin inhibitors. Design of angiotensin transition state analogues containing statine, in Aspartic Proteinases and Their Inhibitors (ed. V. Kostka),Walter de Gruyter, Berlin, pp. 401-420.
28. Kokubu, T., Hiwada, K., Murakami, E., Imamura, Y., Matsueda, R., Yabe, Y., Koike, H., and Iijima, Y. (1985) Highly potent and specific inhibitors of human renin. Hypertension, 7 (Suppl. I), 8-11.
29. Kokubu, T., Hiwada, K., Nagae, A., Murakami, E., Morisawa, Y., Yabe, Y., Koike, H., and Iijima, Y. (1986) Statine containing dipeptide and tripeptide inhibitors of human renin. Hypertension, 8 (Suppl. II), 1-5.
30. Gelb, M.H., Svaren, J.P., and Abeles, R.H. (1985) Fluoroketone inhibitors of hydrolytic enzymes. Biochemistry, 24, 1813. -1817.
31. Szelke, M. (1985) Chemistry of renin inhibitors, in Aspartic Proteinases and Their Inhibitors (ed. V. Kostka), Walter de Gruyter, Berlin, pp. 421-441.
32. Sham, H.L., Stein, H.H., Rempel, C.A., Cohen, J., and Plattner, J.J. (1987) Highly potent and specific inhibitors of human renin. FEBS Letters, 220, 299-301.
33. Cooper, J.B., Foundling, S.I., Blundell, T.L., Boger, J., Jupp, R., and Kay, J. (1989) X-ray studies of aspartic proteinase-statine inhibitor complexes. Biochemistry, 28. , 8596-8603.
34. Arrowsmith, R.J., Carter, K., Dann, J.G., Davies, D.E., Harris, C.J., Morton, J.A., Lister, P., Robinson, J.A., and Williams, D.J. (1986) Novel renin inhibitors: synthesis of aminostatine and comparison with statine-containing analogues. Journal of the Chemical Society: Chemical Communications, 10, 755-757.
35. Jones, M., Sueiras-Diaz, J., Szelke, M., Leckie, B., and Beattie, S. (1985) Renin inhibitors containing the novel amino-acid 3-amino-deoxystatine, in Peptides: Structure and Function (eds C.M. Deber, V.J. Hruby, and K.D. Kopple), Pierce Chemical Company, Rockford, IL, pp. 759-762.
36. Rich, D.H., Sun, E.T.O., and Ulm, E. (1980) Synthesis of analogues of the carboxyl proteinase inhibitor pepstatin. Effect of structure on the inhibition of pepsin and renin. Journal of Medicinal Chemistry, 23, 27-33.
37. Šali, A., Veerapandian, B., Cooper, J.B., Foundling, S.I., Hoover, D.J., and Blundell, T.L. (1989)High resolutionX-ray diffraction study of the complex between endothiapepsin and an oligopeptide inhibitor: the analysis of inhibitor binding and description of the rigid body shifts in the enzyme. The EMBO Journal, 8, 2179. -2188.
38. Iizuka, K., Kamijo, T., Kubota, T., Akahane, K., Umeyama, H., and Kiso, Y. (1988) New human renin inhibitors containing an unnatural amino acid, norstatine. Journal of Medicinal Chemistry, 31. , 701-704.
39. Dann, J.G., Stammers, D.K., Harris, C.J., Arrowsmith, R.J., Davies, D.E., Hardy, G.W., and Morton, J.A. (1986) Human renin: a new class of inhibitors. Biochemical and Biophysical Research Communications, 134, 71-77.
40. Cooper, J.B., Foundling, S.I., Blundell, T.L., Arrowsmith, R.J., Harris, C.J., and Champness, J.N. (1988) A rational approach to the design of antihypertensives: X-ray studies of complexes between aspartic proteinases and aminoalcohol inhibitors, in Topics in Medicinal Chemistry (ed. P.R. Leeming), Royal Society of Chemistry, London, pp. 308. -313.
41. Lunney, E.A., Hamilton, H.W., Hodges, J.C., Kaltenbrohn, J.S., Repine, J.T., Badasso, M., Cooper, J., Dealwis, C., Wallace, B., Lowther, W.T., Dunn, B.M., andHumblet, C. (1993) Analyses of ligand binding in five endothiapepsin crystal complexes and their use in the design and evaluation of novel renin inhibitors. Journal of Medicinal Chemistry, 36, 3809. -3820.
42. Bartlett, P.A. and Kezer, W.B. (1987) Phosphinic acid dipeptide analogues: potent, slow-binding inhibitors of aspartic proteinases. Journal of the American Chemical Society, 106, 4282-4283.
43. Greenlee, W.J. (1987) Renin inhibitors. Pharmaceutical Research, 4, 364-374.
44. Thaisrivongs, S., Pals, D.T., Harris, D.W., Kati,W.M., and Turner, S.R. (1986) Design and synthesis of potent and specific renin inhibitors containing difluorostatine, difluorostatone and related analogues. Journal of Medicinal Chemistry, 29, 2088. -2093.
45. Veerapandian, B., Cooper, J.B., Šali, A., and Blundell, T.L. (1992) Direct observation by X-ray analysis of the tetrahedral 'intermediate' of aspartic proteinases. Protein Science, 1, 322-328.
46. Suguna, K., Padlan, E.A., Smith, C.W., Carlson, W.D., and Davies, D.R. (1987) Binding of a reduced peptide inhibitor to the aspartic proteinase from Rhizopus chinensis: implications for a mechanism of action. Proceedings of the National Academy of Sciences of the United States of America, 84, 7009. -7013.
47. Ptitsyn, O.B. (1973) Thermodynamic parameters of helix-coil transitions in polypeptide chains. Pure and Applied Chemistry, 31, 227-244.
48. Rosenberg, S.H., Plattner, J.J., Woods, K.W., Stein, H.H., Marcotte, P.A., Cohen, J., and Perun, T.J. (1987) Novel renin inhibitors containing analogues of statine retro-inverted at the C-termini: specificity of the P2 histidine site. Journal of Medicinal Chemistry, 30, 1224. -1228.
49. Luly, J.R., Yi, N., Soderquist, J., Stein, H., Cohen, J., Perun, T.J., and Plattner, J.J. (1987)Newinhibitors of human renin that contain novel Leu-Val replacements. Journal of Medicinal Chemistry, 30, 1609. -1616.
50. Cooper, J., Quail, W., Frazao, C., Foundling, S.I., and Blundell, T.L. (1992) X-ray crystallographic analysis of inhibition of endothiapepsin by cyclohexyl renin inhibitors. Biochemistry, 31, 8142. -8150.
51. Cronin, N.B., Badasso, M.O., Tickle, I.J., Dreyer, T., Hoover, D.J., Rosati, R.L., Humblet, C.C., Lunney, E.A., and Cooper, J.B. (2000) X-ray structures of five renin inhibitors bound to saccharopepsin: exploration of active-site specificity. Journal of Molecular Biology, 303, 745-750.
52. Attwood, M.R., Hassall, C.H., Krohn, A., Lawton, G., and Redshaw, S. (1986) The design and synthesis of angiotensin converting enzyme inhibitor cilazapril and related bicyclic compounds. Journal of the Chemical Society: Perkin Transactions 1, 1011. -1019.
53. Sham, H.L., Bolis, G., Stein, H.H., Fesik, S.W., Marcott, P.A., Plattner, J.J., Rempel, C.A., and Greer, J. (1988) Renin inhibitors. Design and synthesis of a new class of conformationally restricted analogues of angiotensinogen. Journal of Medicinal Chemistry, 31, 284-295.
54. Szewczuk, Z., Rebholz, K.L., and Rich, D.H. (1992) Synthesis and biological activity of new conformationally restricted analogues of pepstatin. International Journal of Peptide. Research and Therapeutics, 40, 233-242.
55. Wood, J.M., Fuhrer, W., Buhlmayer, P., Riniker, B., and Hofbauer, K.G. (1985) Protection groups increase the in vivo stability of a statine-containing renin inhibitor, in Aspartic Proteinases and Their Inhibitors (ed. V. Kostka), Walter de Gruyter, Berlin, pp. 463-466.
56. Bolis F G., Fung, A.K.L., Greer, J., Kleinert, H.D.,Marcotte, P.A., Perun, T.J., Plattner, J.J., and Stein, H.H. (1987) Renin inhibitors. Dipeptide analogues of angiotensinogen incorporating transitionstate, nonpeptidic replacements at the scissile bond. Journal of Medicinal Chemistry, 30, 1729-1737.
57. Greenlee, W.J. (1990) Renin inhibitors. Medicinal Research Reviews, 10, 173-236.
58. Sielecki, A.R.,Hayakawa, K., Fujinaga, M., Murphy, M.E.P., Fraser, M., Muir, A.K., Carilli, C.T., Lewicki, J.A., Baxter, J.D., and James, M.N.G. (1989) Structure of recombinant human renin, a target for cardiovascular-active drugs, at 2.5Å resolution. Science, 243, 1346-1351.
59. Dealwis, C.G., Frazao, C., Badasso, M., Cooper, J.B., Tickle, I.J., Driessen, H., Blundell, T.L., Murakami, K., Miyazaki, H., Sueiras-Diaz, J., Jones, D.M., and Szelke, M. (1994) X-ray analysis at 2.0Å resolution of mouse submaxillary renin complexed with a decapeptide inhibitor CH-66, based on the 4. -16 fragment of rat angiotensinogen. Journal of Molecular Biology, 236, 342-360.
60. Tong, L., Pav, S., Lamarre, D., Pilote, L., Laplante, S., Anderson, P.C., and Jung, G. (1995) High resolution crystal-structures of recombinant human renin in complex with polyhydroxymonoamide inhibitors. Journal of Molecular Biology, 250, 211-222.
61. Rahuel, J., Rasetti, V., Maibaum, J., Rueger, H., Goschke, R., Cohen, N.C., Stutz, S., Cumin, F., Fuhrer, W., Wood, J.M., and Grutter, M.G. (2000) Structure-based drug design: the discovery of novel nonpeptide orally active inhibitors of human renin. Chemistry and Biology, 7, 493-504.
62. Wlodawer, A., Miller, M., Jaskolski, M., Sathyanarayana, B.K., Baldwin, E., Weber, I.T., Selk, L.M., Clawson, L., Schneider, J., and Kent, S. (1989) Conserved folding in retroviral proteinases: crystal structure of synthetic HIV-1 proteinase. Science, 245, 616-621.
63. Lapatto, R., Blundell, T.L., Hemmings, A., Overington, J., Wilderspin, A.,Wood, S.P., Merson, J.R., Whittle, P.J., Danley, D.E., Geoghegan, K.F.,Hawrylik, S.J., Lee, S.E., Scheld, K.G., and Hobart, P.M. (1989) X-ray analysis of HIV-1 proteinase at 2.7Å resolution confirms structural homology among retroviral enzymes. Nature, 342, 299. -302.
64. Poe, M., Wu, J.K., Lin, T.-Y., Hoogsteen, K., Bull, H.G., and Slater, E.E. (1984) Renin cleavage of a human-kidney renin substrate analogous to human angiotensinogen that is human renin specific and resistant to cathepsin D. Analytical Biochemistry, 140, 459-467.
65. Cumin, F., Lenguyen, D., Castro, B., Menard, J., and Corvol, P. (1987) Comparative enzymatic studies of human renin acting on pure natural or synthetic substrates. Biochimica et Biophysica Acta, 913. , 10-19.
66. Powers, J.C., Harley, A.D., and Myers, D.V. (1977) Subsite specificity of porcine pepsin, in Acid Proteases: Structure. Function and Biology (ed. J. Tang), Plenum Press, New York, pp. 141. -157.
67. Antonov, V.K. (1977) Acid Proteases: Structure, Function and Biology (ed. J. Tang), Plenum Press, New York, pp. 179-198.
68. Skeggs, L.T., Lentz, K.E., Kahn, J.R., and Hochstrasser, H. (1968) Kinetics of the reaction of renin with nine synthetic peptide substrates. The Journal of Experimental Medicine, 120, 13-34.
69. Holzman, T.F., Chung, C.C., Edalji, R., Egan, D.A., Martin, M., Gubbins, E.J., Krafft, G.A., Wang, G.T., Thomas, A.M., Rosenberg, S.H., and Hutchins, C. (1991) Characterisation of recombinant human renin: kinetics, pH-stability and peptidomimetic inhibitor binding. Journal of Protein Chemistry, 10, 553-563.
70. Staessen, J.A., Li, Y., and Richart, T. (2006) Oral renin inhibitors. Lancet, 368, 1449. -1456.
71. Wood, J.M., Maibaum, J., Rahuel, J., Grutter, M.G., Cohen, N.-C., Rasetti, V., Ruger, H., Goschke, R., Stutz, S., Fuhrer, W., Schilling, W., Rigollier, P., Yamaguchi, Y., Cumin, F., Baum, H.-P., Schnell, C.R., Herold, P., Mah, R., Jensen, C., Obrien, E., Stanton, A., and Bedigian, M.P. (2003) Structure-based design of aliskiren, a novel orally effective renin inhibitor. Biochemical and Biophysical Research Communications, 308, 698. -705.
72. Wlodawer, A. and Vondrasek, J. (1998) Inhibitors of HIV-1 protease: a major success of structure-assisted drug design. Annual Review of Biophysics and Biomolecular Structure, 27, 249-284.
73. De Lucca, G.V., Erickson-Viitanen, S., and Lam, P.Y.S. (1997) Cyclic HIV protease inhibitors capable of displacing the active site structural water molecule. Drug Discovery Today, 2, 6-18.
74. Spaltenstein, A., Kazmierski, W.M., Miller, J.F., and Samano, V. (2005) Discovery of the next generation inhibitors of HIV protease. Current Topics in Medicinal Chemistry, 5, 1589-1607.
75. Wang, W. and Kollman, P. (2001) Computational study of protein specificity: the molecular basis of HIV-1 protease drug resistance. Proceedings of the National Academy of Sciences of the United States of America, 98, 14937-14942.
76. Perelson, A.S., Neumann, A.U., Markowitz, M., Leonard, J.M., and Ho, D.D. (1996) HIV-1 dynamics in vivo: virion clearance rate, infected cell lifespan, and viral generation time. Science, 271. , 1582-1586.
77. Hanessian, S., Yun, H., Hou, Y., Yang, G., Bayrakdarian, M., Therrien, E., Moitessier, N., Roggo, S., Veenstra, S., Tintelnot-Blomley, M., Rondeau, J.M., Ostermeier, C., Strauss, A., Ramage, P., Paganetti, P., Neumann, U., and Betschart, C. (2005) Structure-based design, synthesis, and memapsin 2 (BACE) inhibitory activity of carbocyclic and heterocyclic peptidomimetics. Journal of Medicinal Chemistry, 48, 5175. -5190.
78. Hanessian, S., Yang, G., Rondeau, J.-M., Neumann, U., Betschart, C., and Tintelnot-Blomley, M. (2006) Structurebased design and synthesis of macroheterocyclic peptidomimetic inhibitors of the aspartic protease b-site amyloid precursor protein cleaving enzyme (BACE). Journal of Medicinal Chemistry, 49, 4544-4567.
79. Stachel, S.J., Coburn, C.A., Steele, T.G., Crouthamel, M.-C., Pietrak, B.L., Lai, M.-T., Holloway, M.K., Munshi, S.K., Graham, S.L., and Vacca, J.P. (2006) Conformationally biased P3 amide replacements of b-secretase inhibitors. Bioorganic & Medicinal Chemistry Letters, 16. , 641-644.
80. Yang,W., Lu,W., Lu, Y., Zhong, M., Sun, J., Thomas, A.E., Wilkinson, J.M., Fucini, R.V., Lam, M., Randal, M., Shi, X.-P., Jacobs, J.W., McDowell, R.S., Gordon, E.M., and Ballinger, M.D. (2006) Aminoethylenes: a tetrahedral'intermediate'isostere yielding potent inhibitors of the aspartyl protease BACE-1. Journal of Medicinal Chemistry, 49, 839. -842.
81. Prade, L., Jones, A.F., Boss, C., Richard-Bildstein, S., Meyer, S., Binkert, C., and Bur, D. (2005) X-ray structure of plasmepsin II complexed with a potent achiral inhibitor. The Journal of Biological Chemistry, 280, 23837-23843.
82. Abad-Zapatero, C., Goldman, R., Muchmore, S.W., Hutchins, C., Stewart, K., Navaza, J., Payne, C.D., and Ray, T.L. (1996) Structure of a secreted aspartic protease from C. albicans complexed with a potent inhibitor: implications for the design of antifungal agents. Protein Science, 5, 640-652.
83. Abad-Zapatero, C. and Stewart, K. (2001) Candida proteases and their inhibition: prospects for antifungal therapy. Current Medicinal Chemistry, 8, 941-948.
84. Majer, F., Pavlickova, L., Majer, P., Hradilek, M., Dolejsi, E., Hruskova-Heidingsfeldova, O., and Pichova, I. (2006) Structure-based specificity mapping of secreted aspartic proteases of Candida parapsilosis, Candida albicans and Candida tropicalis using peptidomimetic inhibitors and homology modeling. Biological Chemistry, 387, 1247-1254.
85. James, M.N.G. and Sielecki, A.R. (1986) Molecular-structure of an aspartic proteinase zymogen, porcine pepsinogen, at 1.8Å resolution. Nature, 319, 33-38.
86. Bernstein, N.K., Cherney, M.M., Loetscher, H., Ridley, R.G., and James, M.N.G. (1999) Crystal structure of the novel aspartic proteinase zymogen proplasmepsin II from Plasmodium falciparum. Nature Structural Biology, 6, 32. -37.
87. Lee, A.Y., Gulnik, S.V., and Erickson, J.W. (1998) Conformational switching in an aspartic proteinase. Nature Structural Biology, 5, 866-871.
88. Li, M., Phylip, L.H., Lees, W.E., Winther, J.R., Dunn, B.M., Wlodawer, A., Kay, J., and Gustchina, A. (2000) The aspartic proteinase from Saccharomyces cerevisiae folds its own inhibitor into a helix. Nature Structural Biology, 7, 113-117.
89. Ng, K.K.S., Petersen, J.F.W., Cherney, M.M., Garen, C., Zalatoris, J.J., Rao-Naik, C., Dunn, B.M.,Martzen, M.R., Peanasky, R.J., and James, M.N.G. (2000) Structural basis for the inhibition of porcine pepsin by Ascaris pepsin inhibitor-3. Nature Structural Biology, 7, 653-657.
90. Coates, L., Erskine, P.T., Mall, S., Gill, R., Wood, S.P., Myles, D.A.A., and Cooper, J.B. (2006) X-ray, neutron and NMR studies of the catalytic mechanism of aspartic proteinases. European Biophysics Journal with Biophysics Letters, 35. , 559-566.
91. Adachi, M., Ohhara, T., Kurihara, K., Tamada, T., Honjo, E., Okazaki, N., Arai, S., Shoyama, Y., Kimura, K., Matsumura, H., Sugiyama, S., Adachi, H., Takano, K., Mori, Y., Hidaka, K., Kimura, T., Hayashi, Y., Kiso, Y., and Kuroki, R. (2009) Structure of HIV-1 protease in complex with potent inhibitor KNI-272 determined by high-resolutionXray and neutron crystallography. Proceedings of the National Academy of Sciences of the United States of America, 106, 4641. -4646.
92. Coates, L., Tuan, H.-F., Tomanicek, S., Kovalevsky, A., Mustyakimov, M., Erskine, P.T., and Cooper, J.B. (2008) The catalytic mechanism of an aspartic proteinase explored with neutron and X-ray diffraction. Journal of the American Chemical Society, 130, 7235-7237.