Catalytic water co-existing with a product peptide in the active site of HIV-1 protease revealed by X-ray structure analysis.

ABSTRACT:

Background

It is known that HIV-1 protease is an important target for design of antiviral compounds in the treatment of Acquired Immuno Deficiency Syndrome (AIDS). In this context, understanding the catalytic mechanism of the enzyme is of crucial importance as transition state structure directs inhibitor design. Most mechanistic proposals invoke nucleophilic attack on the scissile peptide bond by a water molecule. But such a water molecule coexisting with any ligand in the active site has not been found so far in the crystal structures.

Principal findings

We report here the first observation of the coexistence in the active site, of a water molecule WAT1, along with the carboxyl terminal product (Q product) peptide. The product peptide has been generated in situ through clea

SUBMITTER: Prashar V 

PROVIDER: S-EPMC2775671 | biostudies-literature | 2009 Nov

REPOSITORIES: biostudies-literature