X-ray analyses of peptide-inhibitor complexes define the structural basis of specificity for human and mouse renins

• Published in: Nature (London) Vol. 357; no. 6378; pp. 466 - 472
• Main Authors: Dhanaraj, V, Dealwis, C. G, 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, O'Connor, B. A, Hoover, D. J
• Format: Journal Article
• Language: English
• Published: London Nature Publishing 11.06.1992; Nature Publishing Group
• Subjects: Amino Acid Sequence; Animals; Binding Sites; Biochemistry; Biological and medical sciences; Chemical Phenomena; Chemistry, Physical; complex; crystal structure; Crystalline structure; Crystallization; Crystals; Drug Design; Fundamental and applied biological sciences. Psychology; Humans; Hydrogen Bonding; inhibitors; man; Mice; Molecular biophysics; Molecular Sequence Data; Molecular Structure; Molecules; Oligopeptides - chemistry; Oligopeptides - metabolism; Protease Inhibitors - chemistry; Protease Inhibitors - metabolism; Protein Binding; Protein Conformation; Proteinase inhibitors; renin; Renin - antagonists & inhibitors; Renin - chemistry; Renin - metabolism; Structure in molecular biology; Substrate Specificity; X-ray crystallography; X-Ray Diffraction; Human; Vertebrata; Mammalia; Renin; Mouse; Enzyme; Rodentia; Inhibitor enzyme complex; Crystallography; X ray diffraction; Crystalline structure
• ISSN: 0028-0836; 1476-4687
• DOI: 10.1038/357466a0

X-ray analyses have defined the three-dimensional structures of crystals of mouse and human renins complexed with peptide inhibitors at resolutions of 1.9 and 2.8 A, respectively. The exquisite specificity of renin arises partly from ordered loop regions at the periphery of the binding cleft. Although the pattern of main-chain hydrogen bonding in other aspartic proteinase inhibitor complexes is conserved in renins, differences in the positions of secondary structure elements (particularly helices) also lead to improved specificity in renins for angiotensinogen substrates.