View source for 1t02


==Crystal structure of a Statin bound to class II HMG-CoA reductase==
<StructureSection load='1t02' size='340' side='right'caption='[[1t02]], [[Resolution|resolution]] 2.60&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[1t02]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Pseudomonas_mevalonii Pseudomonas mevalonii]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1T02 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1T02 FirstGlance]. <br>
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.6&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=LVA:(3R,5R)-7-((1R,2R,6S,8R,8AS)-2,6-DIMETHYL-8-{[(2R)-2-METHYLBUTANOYL]OXY}-1,2,6,7,8,8A-HEXAHYDRONAPHTHALEN-1-YL)-3,5-DIHYDROXYHEPTANOIC+ACID'>LVA</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></td></tr>
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=1t02 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1t02 OCA], [https://pdbe.org/1t02 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1t02 RCSB], [https://www.ebi.ac.uk/pdbsum/1t02 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1t02 ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/MVAA_PSEMV MVAA_PSEMV] P.mevalonii can use mevalonate as sole carbon source. With this enzyme mevalonate is deacetylated to HMG-CoA.
== 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/t0/1t02_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/main_output.php?pdb_ID=1t02 ConSurf].
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== Publication Abstract from PubMed ==
Hydroxymethylglutaryl-CoA (HMG-CoA) reductase is the primary target in the current clinical treatment of hypercholesterolemias with specific inhibitors of the "statin" family. Statins are excellent inhibitors of the class I (human) enzyme but relatively poor inhibitors of the class II enzymes of important bacterial pathogens. To investigate the molecular basis for this difference we determined the x-ray structure of the class II Pseudomonas mevalonii HMG-CoA reductase in complex with the statin drug lovastatin. The structure shows lovastatin bound in the active site and its interactions with residues critically involved in catalysis and substrate binding. Binding of lovastatin also displaces the flap domain of the enzyme, which contains the catalytic residue His-381. Comparison with the structures of statins bound to the human enzyme revealed a similar mode of binding but marked differences in specific interactions that account for the observed differences in affinity. We suggest that these differences might be exploited to develop selective class II inhibitors for use as antibacterial agents against pathogenic microorganisms.

Crystal structure of a statin bound to a class II hydroxymethylglutaryl-CoA reductase.,Tabernero L, Rodwell VW, Stauffacher CV J Biol Chem. 2003 May 30;278(22):19933-8. Epub 2003 Mar 5. PMID:12621048<ref>PMID:12621048</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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<div class="pdbe-citations 1t02" style="background-color:#fffaf0;"></div>

==See Also==
*[[HMG-CoA Reductase 3D structures|HMG-CoA Reductase 3D structures]]
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Large Structures]]
[[Category: Pseudomonas mevalonii]]
[[Category: Rodwell VW]]
[[Category: Stauffacher C]]
[[Category: Tabernero L]]