1c1c
From Proteopedia
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| , resolution 2.5Å | |||||||
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| Ligands: | , | ||||||
| Activity: | RNA-directed DNA polymerase, with EC number 2.7.7.49 | ||||||
| Related: | 1RTV, 1RTH, 1VRU, 1RTI, 1RTJ, 1REV, 1RT1, 1RT2, 1KLM, 1RT3, 1RT4, 1RT5, 1RT6, 1RT7, 1C0T, 1C0U, 1C1B
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| Resources: | FirstGlance, OCA, PDBsum, RCSB | ||||||
| Coordinates: | save as pdb, mmCIF, xml | ||||||
CRYSTAL STRUCTURE OF HIV-1 REVERSE TRANSCRIPTASE IN COMPLEX WITH TNK-6123
Overview
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 Structure
1C1C is a Protein complex structure of sequences from Human immunodeficiency virus 1. Full crystallographic information is available from OCA.
Reference
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
Page seeded by OCA on Sun Mar 30 19:12:29 2008
