1mu2
CRYSTAL STRUCTURE OF HIV-2 REVERSE TRANSCRIPTASE
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OverviewOverview
The HIV-2 serotype of HIV is a cause of disease in parts of the West, African population, and there is evidence for its spread to Europe and, Asia. HIV-2 reverse transcriptase (RT) demonstrates an intrinsic, resistance to non-nucleoside RT inhibitors (NNRTIs), one of two classes of, anti-AIDS drugs that target the viral RT. We report the crystal structure, of HIV-2 RT to 2.35 A resolution, which reveals molecular details of the, resistance to NNRTIs. HIV-2 RT has a similar overall fold to HIV-1 RT but, has structural differences within the "NNRTI pocket" at both conserved and, nonconserved residues. The structure points to the role of sequence, differences that can give rise to unfavorable inhibitor contacts or, destabilization of part of the binding pocket at positions 101, 106, 138, 181, 188, and 190. We also present evidence that the conformation of, Ile-181 compared with the HIV-1 Tyr-181 could be a significant, contributory factor to this inherent drug resistance of HIV-2 to NNRTIs., The availability of a refined structure of HIV-2 RT will provide a, stimulus for the structure-based design of novel non-nucleoside inhibitors, that could be used against HIV-2 infection.
About this StructureAbout this Structure
1MU2 is a Protein complex structure of sequences from Human immunodeficiency virus 1 with SO4 and GOL as ligands. Active as RNA-directed DNA polymerase, with EC number 2.7.7.49 Full crystallographic information is available from OCA.
ReferenceReference
Structure of HIV-2 reverse transcriptase at 2.35-A resolution and the mechanism of resistance to non-nucleoside inhibitors., Ren J, Bird LE, Chamberlain PP, Stewart-Jones GB, Stuart DI, Stammers DK, Proc Natl Acad Sci U S A. 2002 Oct 29;99(22):14410-5. Epub 2002 Oct 17. PMID:12386343
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