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1tv6
From Proteopedia
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|SITE= | |SITE= | ||
|LIGAND= <scene name='pdbligand=CP9:3-[4-(2-METHYL-IMIDAZO[4,5-C]PYRIDIN-1-YL)BENZYL]-3H-BENZOTHIAZOL-2-ONE'>CP9</scene> | |LIGAND= <scene name='pdbligand=CP9:3-[4-(2-METHYL-IMIDAZO[4,5-C]PYRIDIN-1-YL)BENZYL]-3H-BENZOTHIAZOL-2-ONE'>CP9</scene> | ||
| - | |ACTIVITY= [http://en.wikipedia.org/wiki/Sulfate_adenylyltransferase Sulfate adenylyltransferase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.7.4 2.7.7.4] | + | |ACTIVITY= <span class='plainlinks'>[http://en.wikipedia.org/wiki/Sulfate_adenylyltransferase Sulfate adenylyltransferase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.7.4 2.7.7.4] </span> |
|GENE= POL ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id= Human immunodeficiency virus type 1 (isolate BH10)]) | |GENE= POL ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id= Human immunodeficiency virus type 1 (isolate BH10)]) | ||
| + | |DOMAIN= | ||
| + | |RELATEDENTRY=[[3hvt|3HVT]] | ||
| + | |RESOURCES=<span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1tv6 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1tv6 OCA], [http://www.ebi.ac.uk/pdbsum/1tv6 PDBsum], [http://www.rcsb.org/pdb/explore.do?structureId=1tv6 RCSB]</span> | ||
}} | }} | ||
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[[Category: Steitz, T A.]] | [[Category: Steitz, T A.]] | ||
[[Category: Stirtan, W G.]] | [[Category: Stirtan, W G.]] | ||
| - | [[Category: CP9]] | ||
[[Category: transferase]] | [[Category: transferase]] | ||
| - | ''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 00:01:30 2008'' |
Revision as of 21:01, 30 March 2008
| |||||||
| , resolution 2.80Å | |||||||
|---|---|---|---|---|---|---|---|
| Ligands: | |||||||
| Gene: | POL (Human immunodeficiency virus type 1 (isolate BH10)) | ||||||
| Activity: | Sulfate adenylyltransferase, with EC number 2.7.7.4 | ||||||
| Related: | 3HVT
| ||||||
| Resources: | FirstGlance, OCA, PDBsum, RCSB | ||||||
| Coordinates: | save as pdb, mmCIF, xml | ||||||
HIV-1 Reverse Transcriptase Complexed with CP-94,707
Overview
We have determined the crystal structure of the HIV type 1 reverse transcriptase complexed with CP-94,707, a new nonnucleoside reverse transcriptase inhibitor (NNRTI), to 2.8-A resolution. In addition to inhibiting the wild-type enzyme, this compound inhibits mutant enzymes that are resistant to inhibition by nevirapine, efavirenz, and delaviridine. In contrast to other NNRTI complexes where tyrosines 181 and 188 are pointing toward the enzyme active site, the binding pocket in this complex has the tyrosines pointing the opposite direction, as in the unliganded protein structure, to accommodate CP-94,707. This conformation of the pocket has not been observed previously in NNRTI complexes and substantially alters the shape and surface features that are available for interactions with the inhibitor. One ring of CP-94,707 makes extensive stacking interactions with tryptophan 229, one of the few residues in the NNRTI-binding pocket that cannot readily mutate to give rise to drug resistance. In this conformation of the pocket, mutations of tyrosines 181 and 188 are less likely to disrupt inhibitor binding. Modeling the asparagine mutation of lysine 103 shows that a hydrogen bond between it and tyrosine 188 could form as readily in the CP-94,707 complex as it does in the apoenzyme structure, providing an explanation for the activity of this inhibitor against this clinically important mutant.
About this Structure
1TV6 is a Protein complex structure of sequences from Human immunodeficiency virus type 1 (isolate bh10). Full crystallographic information is available from OCA.
Reference
Structure of HIV-1 reverse transcriptase bound to an inhibitor active against mutant reverse transcriptases resistant to other nonnucleoside inhibitors., Pata JD, Stirtan WG, Goldstein SW, Steitz TA, Proc Natl Acad Sci U S A. 2004 Jul 20;101(29):10548-53. Epub 2004 Jul 12. PMID:15249669
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