1s9e: Difference between revisions
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|SITE= | |SITE= | ||
|LIGAND= <scene name='pdbligand=ADB:4-[4-AMINO-6-(2,6-DICHLORO-PHENOXY)-[1,3,5]TRIAZIN-2-YLAMINO]-BENZONITRILE'>ADB</scene> | |LIGAND= <scene name='pdbligand=ADB:4-[4-AMINO-6-(2,6-DICHLORO-PHENOXY)-[1,3,5]TRIAZIN-2-YLAMINO]-BENZONITRILE'>ADB</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= POL ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=11676 Human immunodeficiency virus 1]) | |GENE= POL ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=11676 Human immunodeficiency virus 1]) | ||
|DOMAIN= | |||
|RELATEDENTRY=[[1hnv|1HNV]], [[1hni|1HNI]], [[2hmi|2HMI]], [[1s6q|1S6Q]], [[1s6p|1S6P]], [[1s9e|1S9E]] | |||
|RESOURCES=<span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1s9e FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1s9e OCA], [http://www.ebi.ac.uk/pdbsum/1s9e PDBsum], [http://www.rcsb.org/pdb/explore.do?structureId=1s9e RCSB]</span> | |||
}} | }} | ||
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[[Category: Lewi, P J.]] | [[Category: Lewi, P J.]] | ||
[[Category: Ludovici, D W.]] | [[Category: Ludovici, D W.]] | ||
[[Category: aid]] | [[Category: aid]] | ||
[[Category: drug design]] | [[Category: drug design]] | ||
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[[Category: rt]] | [[Category: rt]] | ||
''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sun Mar 30 23:39:03 2008'' | ||
Revision as of 23:39, 30 March 2008
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| , resolution 2.60Å | |||||||
|---|---|---|---|---|---|---|---|
| Ligands: | |||||||
| Gene: | POL (Human immunodeficiency virus 1) | ||||||
| Activity: | RNA-directed DNA polymerase, with EC number 2.7.7.49 | ||||||
| Related: | 1HNV, 1HNI, 2HMI, 1S6Q, 1S6P, 1S9E
| ||||||
| Resources: | FirstGlance, OCA, PDBsum, RCSB | ||||||
| Coordinates: | save as pdb, mmCIF, xml | ||||||
CRYSTAL STRUCTURE OF HIV-1 REVERSE TRANSCRIPTASE (RT) IN COMPLEX WITH JANSSEN-R129385
OverviewOverview
Anti-AIDS drug candidate and non-nucleoside reverse transcriptase inhibitor (NNRTI) TMC125-R165335 (etravirine) caused an initial drop in viral load similar to that observed with a five-drug combination in naive patients and retains potency in patients infected with NNRTI-resistant HIV-1 variants. TMC125-R165335 and related anti-AIDS drug candidates can bind the enzyme RT in multiple conformations and thereby escape the effects of drug-resistance mutations. Structural studies showed that this inhibitor and other diarylpyrimidine (DAPY) analogues can adapt to changes in the NNRTI-binding pocket in several ways: (1). DAPY analogues can bind in at least two conformationally distinct modes; (2). within a given binding mode, torsional flexibility ("wiggling") of DAPY analogues permits access to numerous conformational variants; and (3). the compact design of the DAPY analogues permits significant repositioning and reorientation (translation and rotation) within the pocket ("jiggling"). Such adaptations appear to be critical for potency against wild-type and a wide range of drug-resistant mutant HIV-1 RTs. Exploitation of favorable components of inhibitor conformational flexibility (such as torsional flexibility about strategically located chemical bonds) can be a powerful drug design concept, especially for designing drugs that will be effective against rapidly mutating targets.
About this StructureAbout this Structure
1S9E is a Protein complex structure of sequences from Human immunodeficiency virus 1. Full crystallographic information is available from OCA.
ReferenceReference
Roles of conformational and positional adaptability in structure-based design of TMC125-R165335 (etravirine) and related non-nucleoside reverse transcriptase inhibitors that are highly potent and effective against wild-type and drug-resistant HIV-1 variants., Das K, Clark AD Jr, Lewi PJ, Heeres J, De Jonge MR, Koymans LM, Vinkers HM, Daeyaert F, Ludovici DW, Kukla MJ, De Corte B, Kavash RW, Ho CY, Ye H, Lichtenstein MA, Andries K, Pauwels R, De Bethune MP, Boyer PL, Clark P, Hughes SH, Janssen PA, Arnold E, J Med Chem. 2004 May 6;47(10):2550-60. PMID:15115397
Page seeded by OCA on Sun Mar 30 23:39:03 2008
Proteopedia Page Contributors and Editors (what is this?)Proteopedia Page Contributors and Editors (what is this?)
OCA- Pages with broken file links
- Human immunodeficiency virus 1
- Protein complex
- RNA-directed DNA polymerase
- Arnold, E.
- Das, K.
- Decorte, B.
- Hughes, S H.
- Janssen, P A.
- Jr., A D.Clark.
- Kukla, M J.
- Lewi, P J.
- Ludovici, D W.
- Aid
- Drug design
- Hiv
- Nnrti
- Nonnucleoside inhibitor
- Protein-inhibitor complex
- R129385
- Reverse transcriptase
- Rt