1rt3

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{{STRUCTURE_1rt3| PDB=1rt3 | SCENE= }}
{{STRUCTURE_1rt3| PDB=1rt3 | SCENE= }}
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'''AZT DRUG RESISTANT HIV-1 REVERSE TRANSCRIPTASE COMPLEXED WITH 1051U91'''
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===AZT DRUG RESISTANT HIV-1 REVERSE TRANSCRIPTASE COMPLEXED WITH 1051U91===
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==Overview==
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HIV reverse transcriptase (RT) is one of the main targets for the action of anti-AIDS drugs. Many of these drugs [e.g., 3'-azido-3'-deoxythymidine (AZT) and 2',3'-dideoxyinosine (ddI)] are analogues of the nucleoside substrates used by the HIV RT. One of the main problems in anti-HIV therapy is the selection of a mutant virus with reduced drug sensitivity. Drug resistance in HIV is generated for nucleoside analogue inhibitors by mutations in HIV RT. However, most of these mutations are situated some distance from the polymerase active site, giving rise to questions concerning the mechanism of resistance. To understand the possible structural bases for this, the crystal structures of AZT- and ddI-resistant RTs have been determined. For the ddI-resistant RT with a mutation at residue 74, no significant conformational changes were observed for the p66 subunit. In contrast, for the AZT-resistant RT (RTMC) bearing four mutations, two of these (at 215 and 219) give rise to a conformational change that propagates to the active site aspartate residues. Thus, these drug resistance mutations produce an effect at the RT polymerase site mediated simply by the protein. It is likely that such long-range effects could represent a common mechanism for generating drug resistance in other systems.
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(as it appears on PubMed at http://www.pubmed.gov), where 9689112 is the PubMed ID number.
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{{ABSTRACT_PUBMED_9689112}}
==About this Structure==
==About this Structure==
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[[Category: Nucleoside inhibitor]]
[[Category: Nucleoside inhibitor]]
[[Category: Nucleotidyltransferase]]
[[Category: Nucleotidyltransferase]]
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Mon Jul 28 03:09:49 2008''

Revision as of 00:09, 28 July 2008

Image:1rt3.png

Template:STRUCTURE 1rt3

AZT DRUG RESISTANT HIV-1 REVERSE TRANSCRIPTASE COMPLEXED WITH 1051U91

Template:ABSTRACT PUBMED 9689112

About this Structure

1RT3 is a Protein complex structure of sequences from Human immunodeficiency virus 1. Full crystallographic information is available from OCA.

Reference

3'-Azido-3'-deoxythymidine drug resistance mutations in HIV-1 reverse transcriptase can induce long range conformational changes., Ren J, Esnouf RM, Hopkins AL, Jones EY, Kirby I, Keeling J, Ross CK, Larder BA, Stuart DI, Stammers DK, Proc Natl Acad Sci U S A. 1998 Aug 4;95(16):9518-23. PMID:9689112

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