3HBO

Crystal structure of chemically synthesized [D-Ala51/51']HIV-1 protease

Summary for 3HBO

• Entry DOI: 10.2210/pdb3hbo/pdb
• Related: 3FSM 3GI0 3HAU 3HAW
• Related PRD ID: PRD_000398
• Descriptor: [D-Ala51/51']HIV-1 protease, N-{(2S)-2-[(N-acetyl-L-threonyl-L-isoleucyl)amino]hexyl}-L-norleucyl-L-glutaminyl-N~5~-[amino(iminio)methyl]-L-ornithinamide (3 entities in total)
• Functional Keywords: beta barrel, hydrolase, hydrolase-hydrolase inhibitor complex, hydrolase/hydrolase inhibitor
• Total number of polymer chains: 2
• Total formula weight: 22234.24

Authors

Torbeev, V.Y.,Kent, S.B.H. (deposition date: 2009-05-04, release date: 2010-05-26, Last modification date: 2012-12-12)

Primary citation

Torbeev, V.Y.,Raghuraman, H.,Hamelberg, D.,Tonelli, M.,Westler, W.M.,Perozo, E.,Kent, S.B.
Protein conformational dynamics in the mechanism of HIV-1 protease catalysis.
Proc.Natl.Acad.Sci.USA, 108:20982-20987, 2011

PubMed Abstract: We have used chemical protein synthesis and advanced physical methods to probe dynamics-function correlations for the HIV-1 protease, an enzyme that has received considerable attention as a target for the treatment of AIDS. Chemical synthesis was used to prepare a series of unique analogues of the HIV-1 protease in which the flexibility of the "flap" structures (residues 37-61 in each monomer of the homodimeric protein molecule) was systematically varied. These analogue enzymes were further studied by X-ray crystallography, NMR relaxation, and pulse-EPR methods, in conjunction with molecular dynamics simulations. We show that conformational isomerization in the flaps is correlated with structural reorganization of residues in the active site, and that it is preorganization of the active site that is a rate-limiting factor in catalysis.

PubMed: 22158985
DOI: 10.1073/pnas.1111202108

Experimental method

X-RAY DIFFRACTION (1.71 Å)