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1.03 A structure of HIV-1 protease: inhibitor binding inside and outside the active site1.03 A structure of HIV-1 protease: inhibitor binding inside and outside the active site
Structural highlights
Evolutionary Conservation Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf. Publication Abstract from PubMedThe X-ray structure of a complex of HIV-1 protease (PR) with a phenylnorstatine inhibitor Z-Pns-Phe-Glu-Glu-NH(2) has been determined at 1.03 A, the highest resolution so far reported for any HIV PR complex. The inhibitor shows subnanomolar K(i) values for both the wild-type PR and the variant representing one of the most common mutations linked to resistance development. The structure comprising the phenylnorstatine moiety of (2R,3S)-chirality displays a unique pattern of hydrogen bonding to the two catalytic aspartate residues. This high resolution makes it possible to assess the donor and acceptor relations of this hydrogen bonding and to indicate a proton shared by the two catalytic residues. A structural mechanism for the unimpaired inhibition of the protease Val82Ala mutant is also suggested, based on energy calculations and analyses. A phenylnorstatine inhibitor binding to HIV-1 protease: geometry, protonation, and subsite-pocket interactions analyzed at atomic resolution.,Brynda J, Rezacova P, Fabry M, Horejsi M, Stouracova R, Sedlacek J, Soucek M, Hradilek M, Lepsik M, Konvalinka J J Med Chem. 2004 Apr 8;47(8):2030-6. PMID:15056001[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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