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1dtt
From Proteopedia
(Difference between revisions)
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| - | [[ | + | ==CRYSTAL STRUCTURE OF HIV-1 REVERSE TRANSCRIPTASE IN COMPLEX WITH PETT-2 (PETT130A94)== |
| + | <StructureSection load='1dtt' size='340' side='right' caption='[[1dtt]], [[Resolution|resolution]] 3.00Å' scene=''> | ||
| + | == Structural highlights == | ||
| + | <table><tr><td colspan='2'>[[1dtt]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Human_immunodeficiency_virus_1 Human immunodeficiency virus 1]. 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><br> | ||
| + | <tr><td class="sblockLbl"><b>[[Non-Standard_Residue|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=CSW:CYSTEINE-S-DIOXIDE'>CSW</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><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> | ||
| + | == Evolutionary Conservation == | ||
| + | [[Image:Consurf_key_small.gif|200px|right]] | ||
| + | Check<jmol> | ||
| + | <jmolCheckbox> | ||
| + | <scriptWhenChecked>select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/dt/1dtt_consurf.spt"</scriptWhenChecked> | ||
| + | <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked> | ||
| + | <text>to colour the structure by Evolutionary Conservation</text> | ||
| + | </jmolCheckbox> | ||
| + | </jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/chain_selection.php?pdb_ID=2ata ConSurf]. | ||
| + | <div style="clear:both"></div> | ||
| + | <div style="background-color:#fffaf0;"> | ||
| + | == Publication Abstract from PubMed == | ||
| + | Most 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<ref>PMID:10681546</ref> | |
| - | + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |
| - | + | </div> | |
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==See Also== | ==See Also== | ||
*[[Reverse transcriptase|Reverse transcriptase]] | *[[Reverse transcriptase|Reverse transcriptase]] | ||
| - | + | == References == | |
| - | == | + | <references/> |
| - | < | + | __TOC__ |
| + | </StructureSection> | ||
[[Category: Human immunodeficiency virus 1]] | [[Category: Human immunodeficiency virus 1]] | ||
[[Category: Balzarini, J.]] | [[Category: Balzarini, J.]] | ||
Revision as of 10:44, 10 September 2014
CRYSTAL STRUCTURE OF HIV-1 REVERSE TRANSCRIPTASE IN COMPLEX WITH PETT-2 (PETT130A94)
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Categories: Human immunodeficiency virus 1 | Balzarini, J. | Bird, L E. | Diprose, J. | Esnouf, R M. | Ikemizu, S. | Milton, J. | Ren, J. | Slater, M. | Stammers, D K. | Stuart, D I. | Warren, J. | Drug design | Hiv-1 reverse transcriptase aid | Hydrolase-transferase complex | Non-nucleoside inhibitor
