1SIV

THREE-DIMENSIONAL STRUCTURE OF A SIV PROTEASE(SLASH)INHIBITOR COMPLEX. IMPLICATIONS FOR THE DESIGN OF HIV-1 AND HIV-2 PROTEASE INHIBITORS

Summary for 1SIV

• Entry DOI: 10.2210/pdb1siv/pdb
• Related PRD ID: PRD_000320
• Descriptor: SIV PROTEASE, methyl N-{(4S,5S)-5-[(L-alanyl-L-alanyl)amino]-4-hydroxy-6-phenylhexanoyl}-L-valyl-L-valinate (3 entities in total)
• Functional Keywords: hydrolase-hydrolase inhibitor complex, acid proteinase, hydrolase/hydrolase inhibitor
• Biological source: Simian immunodeficiency virus
• Total number of polymer chains: 2
• Total formula weight: 22028.61

Authors

Zhao, B.,Abdel-Meguid, S. (deposition date: 1993-08-24, release date: 1994-01-31, Last modification date: 2024-02-14)

Primary citation

Zhao, B.,Winborne, E.,Minnich, M.D.,Culp, J.S.,Debouck, C.,Abdel-Meguid, S.S.
Three-dimensional structure of a simian immunodeficiency virus protease/inhibitor complex. Implications for the design of human immunodeficiency virus type 1 and 2 protease inhibitors.
Biochemistry, 32:13054-13060, 1993

PubMed Abstract: Simian immunodeficiency virus (SIV) proteins have considerable amino acid sequence homology to those from human immunodeficiency virus (HIV); thus monkeys are considered useful models for the preclinical evaluation of acquired immune deficiency syndrome (AIDS) therapeutics. We have crystallized and determined the three-dimensional structure of SIV protease bound to the hydroxyethylene isostere inhibitor SKF107457. Crystals of the complex were grown from 25-32% saturated sodium chloride, by the hanging drop method of vapor diffusion. They belong to the orthorhombic space group I222, with a = 46.3 A, b = 101.5 A, and c = 118.8 A. The structure has been determined at 2.5-A resolution by molecular replacement and refined to a crystallographic discrepancy factor, R (= sigma parallel Fo magnitude of - magnitude of Fc parallel/sigma magnitude of Fo magnitude of), of 0.189. The overall structure of the complex is very similar to previously reported structures of HIV-1 protease bound to inhibitors. The inhibitor is bound in a conformation that is almost identical to that found for the same inhibitor bound to HIV-1 protease, except for an overall translation of the inhibitor, varying along the backbone atoms from about 1.0 A at the termini to about 0.5 A around the scissile bond surrogate. The structures of the SIV and HIV-1 proteins vary significantly only in three surface loops composed of amino acids 15-20, 34-45, and 65-70. Superposition of the 1188 protein backbone atoms from the two structures gives an rms deviation of 1.0 A; this number is reduced to 0.6 A when atoms from the three surface loops are eliminated from the rms calculation.(ABSTRACT TRUNCATED AT 250 WORDS)

PubMed: 8241159
DOI: 10.1021/bi00211a015

Experimental method

X-RAY DIFFRACTION (2.5 Å)