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1c1b
From Proteopedia
(New page: 200px<br /> <applet load="1c1b" size="450" color="white" frame="true" align="right" spinBox="true" caption="1c1b, resolution 2.5Å" /> '''CRYSTAL STRUCTURE OF...) |
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| - | [[Image:1c1b.gif|left|200px]]<br /> | + | [[Image:1c1b.gif|left|200px]]<br /><applet load="1c1b" size="350" color="white" frame="true" align="right" spinBox="true" |
| - | <applet load="1c1b" size=" | + | |
caption="1c1b, resolution 2.5Å" /> | caption="1c1b, resolution 2.5Å" /> | ||
'''CRYSTAL STRUCTURE OF HIV-1 REVERSE TRANSCRIPTASE IN COMPLEX WITH GCA-186'''<br /> | '''CRYSTAL STRUCTURE OF HIV-1 REVERSE TRANSCRIPTASE IN COMPLEX WITH GCA-186'''<br /> | ||
==Overview== | ==Overview== | ||
| - | Two analogues of the nonnucleoside inhibitor of HIV-1 RT, MKC-442 | + | 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== | ==About this Structure== | ||
| - | 1C1B is a [http://en.wikipedia.org/wiki/Protein_complex Protein complex] structure of sequences from [http://en.wikipedia.org/wiki/Human_immunodeficiency_virus_1 Human immunodeficiency virus 1] with GCA as [http://en.wikipedia.org/wiki/ligand ligand]. Active as [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] Full crystallographic information is available from [http:// | + | 1C1B is a [http://en.wikipedia.org/wiki/Protein_complex Protein complex] structure of sequences from [http://en.wikipedia.org/wiki/Human_immunodeficiency_virus_1 Human immunodeficiency virus 1] with <scene name='pdbligand=GCA:'>GCA</scene> as [http://en.wikipedia.org/wiki/ligand ligand]. Active as [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] Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1C1B OCA]. |
==Reference== | ==Reference== | ||
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[[Category: RNA-directed DNA polymerase]] | [[Category: RNA-directed DNA polymerase]] | ||
[[Category: Baba, B.]] | [[Category: Baba, B.]] | ||
| - | [[Category: Hopkins, A | + | [[Category: Hopkins, A L.]] |
[[Category: Okamato, M.]] | [[Category: Okamato, M.]] | ||
[[Category: Ren, J.]] | [[Category: Ren, J.]] | ||
| - | [[Category: Stammers, D | + | [[Category: Stammers, D K.]] |
| - | [[Category: Stuart, D | + | [[Category: Stuart, D I.]] |
[[Category: Tanaka, H.]] | [[Category: Tanaka, H.]] | ||
[[Category: GCA]] | [[Category: GCA]] | ||
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[[Category: transferase]] | [[Category: transferase]] | ||
| - | ''Page seeded by [http:// | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 12:01:20 2008'' |
Revision as of 10:01, 21 February 2008
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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 with as ligand. Active as RNA-directed DNA polymerase, with EC number 2.7.7.49 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 Thu Feb 21 12:01:20 2008
