1c1b
From Proteopedia
| Line 4: | Line 4: | ||
|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',5'-DIMETHYLBENZYL)-1-ETHOXYMETHYL-5-ISOPROPYLURACIL'>GCA</scene> | + | |LIGAND= <scene name='pdbligand=CSW:CYSTEINE-S-DIOXIDE'>CSW</scene>, <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= <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= | |GENE= | ||
| + | |DOMAIN= | ||
| + | |RELATEDENTRY=[[1rtv|1rtv]], [[1rth|1rth]], [[1vru|1vru]], [[1rti|1rti]], [[1rtj|1rtj]], [[1rev|1rev]], [[1rt1|1rt1]], [[1rt2|1rt2]], [[1klm|1klm]], [[1rt3|1rt3]], [[1rt4|1rt4]], [[1rt5|1rt5]], [[1rt6|1rt6]], [[1rt7|1rt7]], [[1c0t|1c0t]], [[1c0u|1c0u]], [[1c1c|1C1C]] | ||
| + | |RESOURCES=<span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1c1b FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1c1b OCA], [http://www.ebi.ac.uk/pdbsum/1c1b PDBsum], [http://www.rcsb.org/pdb/explore.do?structureId=1c1b RCSB]</span> | ||
}} | }} | ||
| Line 30: | Line 33: | ||
[[Category: Stuart, D I.]] | [[Category: Stuart, D I.]] | ||
[[Category: Tanaka, H.]] | [[Category: Tanaka, H.]] | ||
| - | [[Category: GCA]] | ||
[[Category: aid]] | [[Category: aid]] | ||
[[Category: drug design]] | [[Category: drug design]] | ||
| Line 37: | Line 39: | ||
[[Category: transferase]] | [[Category: transferase]] | ||
| - | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sun Mar | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sun Mar 30 19:12:27 2008'' |
Revision as of 16:12, 30 March 2008
| |||||||
| , resolution 2.5Å | |||||||
|---|---|---|---|---|---|---|---|
| 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, 1C1C
| ||||||
| Resources: | FirstGlance, OCA, PDBsum, RCSB | ||||||
| Coordinates: | save as pdb, mmCIF, xml | ||||||
CRYSTAL STRUCTURE OF HIV-1 REVERSE TRANSCRIPTASE IN COMPLEX WITH GCA-186
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
1C1B 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 19:12:27 2008
