1c1b: Difference between revisions
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|PDB= 1c1b |SIZE=350|CAPTION= <scene name='initialview01'>1c1b</scene>, resolution 2.5Å | |PDB= 1c1b |SIZE=350|CAPTION= <scene name='initialview01'>1c1b</scene>, resolution 2.5Å | ||
|SITE= | |SITE= | ||
|LIGAND= <scene name='pdbligand=GCA:6-(3 | |LIGAND= <scene name='pdbligand=GCA:6-(3',5'-DIMETHYLBENZYL)-1-ETHOXYMETHYL-5-ISOPROPYLURACIL'>GCA</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= [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] | ||
|GENE= | |GENE= | ||
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[[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 Sun Mar 23 11:19:16 2008'' | ||
Revision as of 12:19, 23 March 2008
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| , resolution 2.5Å | |||||||
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| Activity: | RNA-directed DNA polymerase, with EC number 2.7.7.49 | ||||||
| Coordinates: | save as pdb, mmCIF, xml | ||||||
CRYSTAL STRUCTURE OF HIV-1 REVERSE TRANSCRIPTASE IN COMPLEX WITH GCA-186
OverviewOverview
Two analogues of the nonnucleoside inhibitor of HIV-1 RT, MKC-442 (emivirine), containing different C6 substituents have been designed to be less susceptible to the commonly found drug-resistance mutation of Tyr181Cys. Compound TNK-6123 had a C6 thiocyclohexyl group designed to have more flexibility in adapting to the mutated drug-binding site. GCA-186 had additional 3',5'-dimethyl substituents aimed at forming close contacts with the conserved residue Trp229. Both compounds showed approximately 30-fold greater inhibitory effect than MKC-442 to the Tyr181Cys mutant virus as well as to the clinically important Lys103Asn virus. X-ray crystallographic structure determination of complexes with HIV-1 RT confirmed the predicted binding modes. These strategies might be used to improve the resilience of other NNRTI series against common drug-resistance mutations.
About this StructureAbout this Structure
1C1B is a Protein complex structure of sequences from Human immunodeficiency virus 1. Full crystallographic information is available from OCA.
ReferenceReference
Design of MKC-442 (emivirine) analogues with improved activity against drug-resistant HIV mutants., Hopkins AL, Ren J, Tanaka H, Baba M, Okamato M, Stuart DI, Stammers DK, J Med Chem. 1999 Nov 4;42(22):4500-5. PMID:10579814
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