3dox

Publication Abstract from PubMed

HIV-1 protease is an effective target for design of different types of drugs against AIDS. HIV-1 protease is also one of the few enzymes that can cleave substrates containing both proline and nonproline residues at the cleavage site. We report here the first structure of HIV-1 protease complexed with the product peptides SQNY and PIV derived by in situ cleavage of the oligopeptide substrate SQNYPIV, within the crystals. In the structure, refined against 2.0-A resolution synchrotron data, a carboxyl oxygen of SQNY is hydrogen-bonded with the N-terminal nitrogen atom of PIV. At the same time, this proline nitrogen atom does not form any hydrogen bond with catalytic aspartates. These two observations suggest that the protonation of scissile nitrogen, during peptide bond cleavage, is by a gem-hydroxyl of the tetrahedral intermediate rather than by a catalytic aspartic acid. Proteins 2008. (c) 2008 Wiley-Liss, Inc.

X-ray structure of HIV-1 protease in situ product complex.,Bihani S, Das A, Prashar V, Ferrer JL, Hosur MV Proteins. 2008 Aug 14. PMID:18704947^[1]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.