This old version of Proteopedia is provided for student assignments while the new version is undergoing repairs. Content and edits done in this old version of Proteopedia after March 1, 2026 will eventually be lost when it is retired in about June of 2026.
Apply for new accounts at the new Proteopedia. Your logins will work in both the old and new versions.
2p3d
From Proteopedia
| Line 1: | Line 1: | ||
[[Image:2p3d.gif|left|200px]] | [[Image:2p3d.gif|left|200px]] | ||
| - | + | <!-- | |
| - | + | The line below this paragraph, containing "STRUCTURE_2p3d", creates the "Structure Box" on the page. | |
| - | + | You may change the PDB parameter (which sets the PDB file loaded into the applet) | |
| - | + | or the SCENE parameter (which sets the initial scene displayed when the page is loaded), | |
| - | + | or leave the SCENE parameter empty for the default display. | |
| - | | | + | --> |
| - | | | + | {{STRUCTURE_2p3d| PDB=2p3d | SCENE= }} |
| - | + | ||
| - | + | ||
| - | }} | + | |
'''Crystal Structure of the multi-drug resistant mutant subtype F HIV protease complexed with TL-3 inhibitor''' | '''Crystal Structure of the multi-drug resistant mutant subtype F HIV protease complexed with TL-3 inhibitor''' | ||
| Line 19: | Line 16: | ||
==About this Structure== | ==About this Structure== | ||
| - | + | Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2P3D OCA]. | |
==Reference== | ==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:[http://www.ncbi.nlm.nih.gov/pubmed/17467738 17467738] | 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:[http://www.ncbi.nlm.nih.gov/pubmed/17467738 17467738] | ||
[[Category: HIV-1 retropepsin]] | [[Category: HIV-1 retropepsin]] | ||
| - | [[Category: Human immunodeficiency virus 1]] | ||
| - | [[Category: Protein complex]] | ||
[[Category: Gustchina, A.]] | [[Category: Gustchina, A.]] | ||
[[Category: Krauchenco, S.]] | [[Category: Krauchenco, S.]] | ||
| Line 32: | Line 27: | ||
[[Category: Sanches, M.]] | [[Category: Sanches, M.]] | ||
[[Category: Wlodawer, A.]] | [[Category: Wlodawer, A.]] | ||
| - | [[Category: | + | [[Category: Multi-drug resistant mutant subtype f hiv protease]] |
| - | [[Category: | + | [[Category: Non-b hiv protease]] |
| - | [[Category: | + | [[Category: Protease-inhibitor complex]] |
| - | [[Category: | + | [[Category: Tl-3 inhibitor]] |
| - | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sun May 4 12:15:37 2008'' | |
| - | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on | + | |
Revision as of 09:15, 4 May 2008
Crystal Structure of the multi-drug resistant mutant subtype F 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
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 Page seeded by OCA on Sun May 4 12:15:37 2008
