1dtt: Difference between revisions
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<StructureSection load='1dtt' size='340' side='right' caption='[[1dtt]], [[Resolution|resolution]] 3.00Å' scene=''> | <StructureSection load='1dtt' size='340' side='right' caption='[[1dtt]], [[Resolution|resolution]] 3.00Å' scene=''> | ||
== Structural highlights == | == Structural highlights == | ||
<table><tr><td colspan='2'>[[1dtt]] is a 2 chain structure | <table><tr><td colspan='2'>[[1dtt]] is a 2 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1DTT OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1DTT FirstGlance]. <br> | ||
</td></tr><tr><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=FTC:N-[[3-FLUORO-4-ETHOXY-PYRID-2-YL]ETHYL]-N-[5-CHLORO-PYRIDYL]-THIOUREA'>FTC</scene>< | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=FTC:N-[[3-FLUORO-4-ETHOXY-PYRID-2-YL]ETHYL]-N-[5-CHLORO-PYRIDYL]-THIOUREA'>FTC</scene></td></tr> | ||
<tr><td class="sblockLbl"><b>[[Non-Standard_Residue|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand= | <tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=CSD:3-SULFINOALANINE'>CSD</scene></td></tr> | ||
<tr><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[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]], [[1c1b|1c1b]], [[1c1c|1c1c]], [[1dtq|1dtq]]</td></tr> | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[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]], [[1c1b|1c1b]], [[1c1c|1c1c]], [[1dtq|1dtq]]</td></tr> | ||
<tr><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1dtt FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1dtt OCA], [http://www.rcsb.org/pdb/explore.do?structureId=1dtt RCSB], [http://www.ebi.ac.uk/pdbsum/1dtt PDBsum]</span></td></tr> | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1dtt FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1dtt OCA], [http://www.rcsb.org/pdb/explore.do?structureId=1dtt RCSB], [http://www.ebi.ac.uk/pdbsum/1dtt PDBsum]</span></td></tr> | ||
<table> | </table> | ||
== Evolutionary Conservation == | == Evolutionary Conservation == | ||
[[Image:Consurf_key_small.gif|200px|right]] | [[Image:Consurf_key_small.gif|200px|right]] | ||
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__TOC__ | __TOC__ | ||
</StructureSection> | </StructureSection> | ||
[[Category: Balzarini, J]] | |||
[[Category: Balzarini, J | [[Category: Bird, L E]] | ||
[[Category: Bird, L E | [[Category: Diprose, J]] | ||
[[Category: Diprose, J | [[Category: Esnouf, R M]] | ||
[[Category: Esnouf, R M | [[Category: Ikemizu, S]] | ||
[[Category: Ikemizu, S | [[Category: Milton, J]] | ||
[[Category: Milton, J | [[Category: Ren, J]] | ||
[[Category: Ren, J | [[Category: Slater, M]] | ||
[[Category: Slater, M | [[Category: Stammers, D K]] | ||
[[Category: Stammers, D K | [[Category: Stuart, D I]] | ||
[[Category: Stuart, D I | [[Category: Warren, J]] | ||
[[Category: Warren, J | |||
[[Category: Drug design]] | [[Category: Drug design]] | ||
[[Category: Hiv-1 reverse transcriptase aid]] | [[Category: Hiv-1 reverse transcriptase aid]] | ||
[[Category: Hydrolase-transferase complex]] | [[Category: Hydrolase-transferase complex]] | ||
[[Category: Non-nucleoside inhibitor]] | [[Category: Non-nucleoside inhibitor]] | ||
Revision as of 10:08, 12 November 2014
CRYSTAL STRUCTURE OF HIV-1 REVERSE TRANSCRIPTASE IN COMPLEX WITH PETT-2 (PETT130A94)CRYSTAL STRUCTURE OF HIV-1 REVERSE TRANSCRIPTASE IN COMPLEX WITH PETT-2 (PETT130A94)
Structural highlights
Evolutionary Conservation Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf. Publication Abstract from PubMedMost non-nucleoside reverse transcriptase (RT) inhibitors are specific for HIV-1 RT and demonstrate minimal inhibition of HIV-2 RT. However, we report that members of the phenylethylthiazolylthiourea (PETT) series of non-nucleoside reverse transcriptase inhibitors showing high potency against HIV-1 RT have varying abilities to inhibit HIV-2 RT. Thus, PETT-1 inhibits HIV-1 RT with an IC(50) of 6 nM but shows only weak inhibition of HIV-2 RT, whereas PETT-2 retains similar potency against HIV-1 RT (IC(50) of 5 nM) and also inhibits HIV-2 RT (IC(50) of 2.2 microM). X-ray crystallographic structure determinations of PETT-1 and PETT-2 in complexes with HIV-1 RT reveal the compounds bind in an overall similar conformation albeit with some differences in their interactions with the protein. To investigate whether PETT-2 could be acting at a different site on HIV-2 RT (e.g. the dNTP or template primer binding site), we compared modes of inhibition for PETT-2 against HIV-1 and HIV-2 RT. PETT-2 was a noncompetitive inhibitor with respect to the dGTP substrate for both HIV-1 and HIV-2 RTs. PETT-2 was also a noncompetitive inhibitor with respect to a poly(rC).(dG) template primer for HIV-2 RT. These results are consistent with PETT-2 binding in corresponding pockets in both HIV-1 and HIV-2 RT with amino acid sequence differences in HIV-2 RT affecting the binding of PETT-2 compared with PETT-1. Phenylethylthiazolylthiourea (PETT) non-nucleoside inhibitors of HIV-1 and HIV-2 reverse transcriptases. Structural and biochemical analyses.,Ren J, Diprose J, Warren J, Esnouf RM, Bird LE, Ikemizu S, Slater M, Milton J, Balzarini J, Stuart DI, Stammers DK J Biol Chem. 2000 Feb 25;275(8):5633-9. PMID:10681546[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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