View source for 1dtq

==CRYSTAL STRUCTURE OF HIV-1 REVERSE TRANSCRIPTASE IN COMPLEX WITH PETT-1 (PETT131A94)==
<StructureSection load='1dtq' size='340' side='right' caption='[[1dtq]], [[Resolution|resolution]] 2.80&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[1dtq]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/9hiv1 9hiv1]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1DTQ OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1DTQ FirstGlance]. <br>
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=FPT:N-[[3-FLUORO-4-ETHOXY-PYRID-2-YL]ETHYL]-N-[5-NITRILOMETHYL-PYRIDYL]-THIOUREA'>FPT</scene></td></tr>
<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 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]], [[1dtt|1dtt]]</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=1dtq FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1dtq OCA], [http://www.rcsb.org/pdb/explore.do?structureId=1dtq RCSB], [http://www.ebi.ac.uk/pdbsum/1dtq 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/1dtq_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&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>

==See Also==
*[[Reverse transcriptase|Reverse transcriptase]]
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Balzarini, J]]
[[Category: Bird, L E]]
[[Category: Diprose, J]]
[[Category: Esnouf, R M]]
[[Category: Ikemizu, S]]
[[Category: Milton, J]]
[[Category: Ren, J]]
[[Category: Slater, M]]
[[Category: Stammers, D K]]
[[Category: Stuart, D I]]
[[Category: Warren, J]]
[[Category: Drug design]]
[[Category: Hiv-1 reverse transcriptase aid]]
[[Category: Hydrolase-transferase complex]]
[[Category: Non-nucleoside inhibitor]]