1SDU

Crystal structures of HIV protease V82A and L90M mutants reveal changes in indinavir binding site.

Summary for 1SDU

• Entry DOI: 10.2210/pdb1sdu/pdb
• Related: 1FF0 1SDT 1SDV
• Descriptor: protease RETROPEPSIN, SULFATE ION, ACETATE ION, ... (5 entities in total)
• Functional Keywords: drug resistance hiv-1 protease, hydrolase
• Biological source: Human immunodeficiency virus 1
• Cellular location: Matrix protein p17: Virion (Potential). Capsid protein p24: Virion (Potential). Nucleocapsid protein p7: Virion (Potential). Reverse transcriptase/ribonuclease H: Virion (Potential). Integrase: Virion (Potential): P03367
• Total number of polymer chains: 2
• Total formula weight: 22286.33

Authors

Mahalingam, B.,Wang, Y.-F.,Boross, P.I.,Tozser, J.,Louis, J.M.,Harrison, R.W.,Weber, I.T. (deposition date: 2004-02-14, release date: 2004-05-25, Last modification date: 2024-02-14)

Primary citation

Mahalingam, B.,Wang, Y.-F.,Boross, P.I.,Tozser, J.,Louis, J.M.,Harrison, R.W.,Weber, I.T.
Crystal structures of HIV protease V82A and L90M mutants reveal changes in the indinavir-binding site
Eur.J.Biochem., 271:1516-1524, 2004

PubMed Abstract: The crystal structures of the wild-type HIV-1 protease (PR) and the two resistant variants, PR(V82A) and PR(L90M), have been determined in complex with the antiviral drug, indinavir, to gain insight into the molecular basis of drug resistance. V82A and L90M correspond to an active site mutation and nonactive site mutation, respectively. The inhibition (K(i)) of PR(V82A) and PR(L90M) was 3.3- and 0.16-fold, respectively, relative to the value for PR. They showed only a modest decrease, of 10-15%, in their k(cat)/K(m) values relative to PR. The crystal structures were refined to resolutions of 1.25-1.4 A to reveal critical features associated with inhibitor resistance. PR(V82A) showed local changes in residues 81-82 at the site of the mutation, while PR(L90M) showed local changes near Met90 and an additional interaction with indinavir. These structural differences concur with the kinetic data.

PubMed: 15066177
DOI: 10.1111/j.1432-1033.2004.04060.x

Experimental method

X-RAY DIFFRACTION (1.25 Å)