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[[Image:3klg.png|left|200px]]
==Crystal structure of AZT-resistant HIV-1 Reverse Transcriptase crosslinked to pre-translocation AZTMP-Terminated DNA (COMPLEX N)==
<StructureSection load='3klg' size='340' side='right' caption='[[3klg]], [[Resolution|resolution]] 3.65&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[3klg]] is a 8 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=3KLG OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3KLG FirstGlance]. <br>
</td></tr><tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=ATM:3-AZIDO-3-DEOXYTHYMIDINE-5-MONOPHOSPHATE'>ATM</scene>, <scene name='pdbligand=MRG:N2-(3-MERCAPTOPROPYL)-2-DEOXYGUANOSINE-5-MONOPHOSPHATE'>MRG</scene></td></tr>
<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[3kle|3kle]], [[3klf|3klf]], [[3klh|3klh]], [[3kli|3kli]]</td></tr>
<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">gag-pol ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=11676 Human immunodeficiency virus 1])</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=3klg FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3klg OCA], [http://www.rcsb.org/pdb/explore.do?structureId=3klg RCSB], [http://www.ebi.ac.uk/pdbsum/3klg 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/kl/3klg_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 ==
Human immunodeficiency virus (HIV-1) develops resistance to 3'-azido-2',3'-deoxythymidine (AZT, zidovudine) by acquiring mutations in reverse transcriptase that enhance the ATP-mediated excision of AZT monophosphate from the 3' end of the primer. The excision reaction occurs at the dNTP-binding site, uses ATP as a pyrophosphate donor, unblocks the primer terminus and allows reverse transcriptase to continue viral DNA synthesis. The excision product is AZT adenosine dinucleoside tetraphosphate (AZTppppA). We determined five crystal structures: wild-type reverse transcriptase-double-stranded DNA (RT-dsDNA)-AZTppppA; AZT-resistant (AZTr; M41L D67N K70R T215Y K219Q) RT-dsDNA-AZTppppA; AZTr RT-dsDNA terminated with AZT at dNTP- and primer-binding sites; and AZTr apo reverse transcriptase. The AMP part of AZTppppA bound differently to wild-type and AZTr reverse transcriptases, whereas the AZT triphosphate part bound the two enzymes similarly. Thus, the resistance mutations create a high-affinity ATP-binding site. The structure of the site provides an opportunity to design inhibitors of AZT-monophosphate excision.


{{STRUCTURE_3klg|  PDB=3klg  |  SCENE=  }}
Structural basis of HIV-1 resistance to AZT by excision.,Tu X, Das K, Han Q, Bauman JD, Clark AD Jr, Hou X, Frenkel YV, Gaffney BL, Jones RA, Boyer PL, Hughes SH, Sarafianos SG, Arnold E Nat Struct Mol Biol. 2010 Oct;17(10):1202-9. Epub 2010 Sep 19. PMID:20852643<ref>PMID:20852643</ref>


===Crystal structure of AZT-resistant HIV-1 Reverse Transcriptase crosslinked to pre-translocation AZTMP-Terminated DNA (COMPLEX N)===
From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
 
</div>
{{ABSTRACT_PUBMED_20852643}}
 
==About this Structure==
[[3klg]] is a 8 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=3KLG OCA].


==See Also==
==See Also==
*[[AZT-resistant HIV-1 reverse transcriptase|AZT-resistant HIV-1 reverse transcriptase]]
*[[AZT-resistant HIV-1 reverse transcriptase|AZT-resistant HIV-1 reverse transcriptase]]
*[[Reverse transcriptase|Reverse transcriptase]]
*[[Reverse transcriptase|Reverse transcriptase]]
 
== References ==
==Reference==
<references/>
<ref group="xtra">PMID:020852643</ref><references group="xtra"/>
__TOC__
</StructureSection>
[[Category: Human immunodeficiency virus 1]]
[[Category: Human immunodeficiency virus 1]]
[[Category: Arnold, E.]]
[[Category: Arnold, E]]
[[Category: Sarafianos, S G.]]
[[Category: Sarafianos, S G]]
[[Category: Tu, X.]]
[[Category: Tu, X]]
[[Category: Aid]]
[[Category: Aid]]
[[Category: Azt]]
[[Category: Azt]]
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