2opq: Difference between revisions
No edit summary |
No edit summary |
||
| Line 4: | Line 4: | ||
|PDB= 2opq |SIZE=350|CAPTION= <scene name='initialview01'>2opq</scene>, resolution 2.80Å | |PDB= 2opq |SIZE=350|CAPTION= <scene name='initialview01'>2opq</scene>, resolution 2.80Å | ||
|SITE= | |SITE= | ||
|LIGAND= <scene name='pdbligand= | |LIGAND= <scene name='pdbligand=CSW:CYSTEINE-S-DIOXIDE'>CSW</scene>, <scene name='pdbligand=HBQ:ISOPROPYL+(2S)-2-ETHYL-7-FLUORO-3-OXO-3,4-DIHYDROQUINOXALINE-1(2H)-CARBOXYLATE'>HBQ</scene>, <scene name='pdbligand=PO4:PHOSPHATE+ION'>PO4</scene> | ||
|ACTIVITY= [http://en.wikipedia.org/wiki/RNA-directed_DNA_polymerase RNA-directed DNA polymerase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.7.49 2.7.7.49] | |ACTIVITY= <span class='plainlinks'>[http://en.wikipedia.org/wiki/RNA-directed_DNA_polymerase RNA-directed DNA polymerase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.7.49 2.7.7.49] </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= | |||
|RESOURCES=<span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2opq FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2opq OCA], [http://www.ebi.ac.uk/pdbsum/2opq PDBsum], [http://www.rcsb.org/pdb/explore.do?structureId=2opq RCSB]</span> | |||
}} | }} | ||
| Line 31: | Line 34: | ||
[[Category: Stammers, D K.]] | [[Category: Stammers, D K.]] | ||
[[Category: Weaver, K L.]] | [[Category: Weaver, K L.]] | ||
[[Category: aid]] | [[Category: aid]] | ||
[[Category: drug resistance]] | [[Category: drug resistance]] | ||
| Line 39: | Line 40: | ||
[[Category: nnrti]] | [[Category: nnrti]] | ||
''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 04:21:20 2008'' | ||
Revision as of 04:21, 31 March 2008
| |||||||
| , resolution 2.80Å | |||||||
|---|---|---|---|---|---|---|---|
| Ligands: | , , | ||||||
| Gene: | gag-pol (Human immunodeficiency virus 1) | ||||||
| Activity: | RNA-directed DNA polymerase, with EC number 2.7.7.49 | ||||||
| Resources: | FirstGlance, OCA, PDBsum, RCSB | ||||||
| Coordinates: | save as pdb, mmCIF, xml | ||||||
Crystal Structure of L100I Mutant HIV-1 Reverse Transcriptase in Complex with GW420867X.
OverviewOverview
The selection of drug resistant viruses is a major problem in efforts to combat HIV and AIDS, hence, new compounds are required. We report crystal structures of wild-type and mutant HIV-1 RT with bound non-nucleoside (NNRTI) GW420867X, aimed at investigating the basis for its high potency and improved drug resistance profile compared to the first-generation drug nevirapine. GW420867X occupies a smaller volume than many NNRTIs, yet accesses key regions of the binding pocket. GW420867X has few contacts with Tyr188, hence, explaining the small effect of mutating this residue on inhibitor-binding potency. In a mutated NNRTI pocket, GW420867X either remains in a similar position compared to wild-type (RT(Leu100Ile) and RT(Tyr188Cys)) or rearranges within the pocket (RT(Lys101Glu)). For RT(Leu100Ile), GW420867X does not shift position, in spite of forming different side-chain contacts. The small bulk of GW420867X allows adaptation to a mutated NNRTI binding site by repositioning or readjustment of side-chain contacts with only small reductions in binding affinity.
About this StructureAbout this Structure
2OPQ is a Protein complex structure of sequences from Human immunodeficiency virus 1. Full crystallographic information is available from OCA.
ReferenceReference
Relationship of potency and resilience to drug resistant mutations for GW420867X revealed by crystal structures of inhibitor complexes for wild-type, Leu100Ile, Lys101Glu, and Tyr188Cys mutant HIV-1 reverse transcriptases., Ren J, Nichols CE, Chamberlain PP, Weaver KL, Short SA, Chan JH, Kleim JP, Stammers DK, J Med Chem. 2007 May 17;50(10):2301-9. Epub 2007 Apr 19. PMID:17441703
Page seeded by OCA on Mon Mar 31 04:21:20 2008