2p3c
From Proteopedia
(New page: 200px<br /> <applet load="2p3c" size="450" color="white" frame="true" align="right" spinBox="true" caption="2p3c, resolution 2.100Å" /> '''Crystal Structure ...) |
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caption="2p3c, resolution 2.100Å" /> | caption="2p3c, resolution 2.100Å" /> | ||
'''Crystal Structure of the subtype F wild type HIV protease complexed with TL-3 inhibitor'''<br /> | '''Crystal Structure of the subtype F wild type HIV protease complexed with TL-3 inhibitor'''<br /> | ||
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==About this Structure== | ==About this Structure== | ||
| - | 2P3C is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Human_immunodeficiency_virus_1 Human immunodeficiency virus 1] with 3TL and ACY as [http://en.wikipedia.org/wiki/ligands ligands]. Active as [http://en.wikipedia.org/wiki/HIV-1_retropepsin HIV-1 retropepsin], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.4.23.16 3.4.23.16] Full crystallographic information is available from [http:// | + | 2P3C is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Human_immunodeficiency_virus_1 Human immunodeficiency virus 1] with <scene name='pdbligand=3TL:'>3TL</scene> and <scene name='pdbligand=ACY:'>ACY</scene> as [http://en.wikipedia.org/wiki/ligands ligands]. Active as [http://en.wikipedia.org/wiki/HIV-1_retropepsin HIV-1 retropepsin], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.4.23.16 3.4.23.16] Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2P3C OCA]. |
==Reference== | ==Reference== | ||
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[[Category: wild type subtype f hiv protease]] | [[Category: wild type subtype f hiv protease]] | ||
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Revision as of 13:05, 23 January 2008
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Crystal Structure of the subtype F wild type HIV protease complexed with TL-3 inhibitor
Overview
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.
About this Structure
2P3C is a Single protein structure of sequence from Human immunodeficiency virus 1 with and as ligands. Active as HIV-1 retropepsin, with EC number 3.4.23.16 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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