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2p3d

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{{STRUCTURE_2p3d| PDB=2p3d | SCENE= }}
{{STRUCTURE_2p3d| PDB=2p3d | SCENE= }}
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'''Crystal Structure of the multi-drug resistant mutant subtype F HIV protease complexed with TL-3 inhibitor'''
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===Crystal Structure of the multi-drug resistant mutant subtype F HIV protease complexed with TL-3 inhibitor===
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==Overview==
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Although a majority of HIV-1 infections in Brazil are caused by the subtype B virus (also prevalent in the United States and Western Europe), viral subtypes F and C are also found very frequently. Genomic differences between the subtypes give rise to sequence variations in the encoded proteins, including the HIV-1 protease. The current anti-HIV drugs have been developed primarily against subtype B and the effects arising from the combination of drug-resistance mutations with the naturally existing polymorphisms in non-B HIV-1 subtypes are only beginning to be elucidated. To gain more insights into the structure and function of different variants of HIV proteases, we have determined a 2.1 A structure of the native subtype F HIV-1 protease (PR) in complex with the protease inhibitor TL-3. We have also solved crystal structures of two multi-drug resistant mutant HIV PRs in complex with TL-3, from subtype B (Bmut) carrying the primary mutations V82A and L90M, and from subtype F (Fmut) carrying the primary mutation V82A plus the secondary mutation M36I, at 1.75 A and 2.8 A resolution, respectively. The proteases Bmut, Fwt and Fmut exhibit sevenfold, threefold, and 54-fold resistance to TL-3, respectively. In addition, the structure of subtype B wild type HIV-PR in complex with TL-3 has been redetermined in space group P6(1), consistent with the other three structures. Our results show that the primary mutation V82A causes the known effect of collapsing the S1/S1' pockets that ultimately lead to the reduced inhibitory effect of TL-3. Our results further indicate that two naturally occurring polymorphic substitutions in subtype F and other non-B HIV proteases, M36I and L89M, may lead to early development of drug resistance in patients infected with non-B HIV subtypes.
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(as it appears on PubMed at http://www.pubmed.gov), where 17467738 is the PubMed ID number.
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{{ABSTRACT_PUBMED_17467738}}
==About this Structure==
==About this Structure==
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[[Category: Protease-inhibitor complex]]
[[Category: Protease-inhibitor complex]]
[[Category: Tl-3 inhibitor]]
[[Category: Tl-3 inhibitor]]
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Mon Jul 28 21:24:44 2008''

Revision as of 18:24, 28 July 2008

Image:2p3d.png

Template:STRUCTURE 2p3d

Crystal Structure of the multi-drug resistant mutant subtype F HIV protease complexed with TL-3 inhibitor

Template:ABSTRACT PUBMED 17467738

About this Structure

Full crystallographic information is available from OCA.

Reference

Structural characterization of B and non-B subtypes of HIV-protease: insights into the natural susceptibility to drug resistance development., Sanches M, Krauchenco S, Martins NH, Gustchina A, Wlodawer A, Polikarpov I, J Mol Biol. 2007 Jun 15;369(4):1029-40. Epub 2007 Mar 24. PMID:17467738

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