2p3b
From Proteopedia
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|PDB= 2p3b |SIZE=350|CAPTION= <scene name='initialview01'>2p3b</scene>, resolution 2.100Å | |PDB= 2p3b |SIZE=350|CAPTION= <scene name='initialview01'>2p3b</scene>, resolution 2.100Å | ||
|SITE= | |SITE= | ||
| - | |LIGAND= <scene name='pdbligand=3TL:BENZYL (2S,5S,8S,9R,10R,11S,14S,17S)-8,11-DIBENZYL-9,10-DIHYDROXY-5,14-DIISOPROPYL-3,6,13,16-TETRAOXO-4,7,12,15-TETRAAZAOCTADECANE-2,17-DIYLDICARBAMATE'>3TL</scene> | + | |LIGAND= <scene name='pdbligand=3TL:BENZYL+(2S,5S,8S,9R,10R,11S,14S,17S)-8,11-DIBENZYL-9,10-DIHYDROXY-5,14-DIISOPROPYL-3,6,13,16-TETRAOXO-4,7,12,15-TETRAAZAOCTADECANE-2,17-DIYLDICARBAMATE'>3TL</scene>, <scene name='pdbligand=CME:S,S-(2-HYDROXYETHYL)THIOCYSTEINE'>CME</scene> |
| - | |ACTIVITY= [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] | + | |ACTIVITY= <span class='plainlinks'>[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] </span> |
|GENE= gag-pol ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=11676 Human immunodeficiency virus 1]) | |GENE= gag-pol ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=11676 Human immunodeficiency virus 1]) | ||
| + | |DOMAIN= | ||
| + | |RELATEDENTRY=[[3tlh|3TLH]], [[2p3a|2P3A]] | ||
| + | |RESOURCES=<span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2p3b FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2p3b OCA], [http://www.ebi.ac.uk/pdbsum/2p3b PDBsum], [http://www.rcsb.org/pdb/explore.do?structureId=2p3b RCSB]</span> | ||
}} | }} | ||
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[[Category: Sanches, M.]] | [[Category: Sanches, M.]] | ||
[[Category: Wlodawer, A.]] | [[Category: Wlodawer, A.]] | ||
| - | [[Category: 3TL]] | ||
[[Category: protease-inhibitor complex]] | [[Category: protease-inhibitor complex]] | ||
[[Category: tl-3 inhibitor]] | [[Category: tl-3 inhibitor]] | ||
[[Category: wild type subtype b hiv protease]] | [[Category: wild type subtype b hiv protease]] | ||
| - | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Mon Mar 31 04:28:18 2008'' |
Revision as of 01:28, 31 March 2008
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| , resolution 2.100Å | |||||||
|---|---|---|---|---|---|---|---|
| Ligands: | , | ||||||
| Gene: | gag-pol (Human immunodeficiency virus 1) | ||||||
| Activity: | HIV-1 retropepsin, with EC number 3.4.23.16 | ||||||
| Related: | 3TLH, 2P3A
| ||||||
| Resources: | FirstGlance, OCA, PDBsum, RCSB | ||||||
| Coordinates: | save as pdb, mmCIF, xml | ||||||
Crystal Structure of the subtype B 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
2P3B is a Protein complex structure of sequences from Human immunodeficiency virus 1. 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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