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1kpi

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[[Image:1kpi.gif|left|200px]]<br /><applet load="1kpi" size="350" color="white" frame="true" align="right" spinBox="true"
 
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caption="1kpi, resolution 2.65&Aring;" />
 
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'''Crystal Structure of mycolic acid cyclopropane synthase CmaA2 complexed with SAH and DDDMAB'''<br />
 
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==Overview==
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==Crystal Structure of mycolic acid cyclopropane synthase CmaA2 complexed with SAH and DDDMAB==
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Mycolic acids are major components of the cell wall of Mycobacterium tuberculosis. Several studies indicate that functional groups in the acyl chain of mycolic acids are important for pathogenesis and persistence. There are at least three mycolic acid cyclopropane synthases (PcaA, CmaA1, and CmaA2) that are responsible for these site-specific modifications of mycolic acids. To derive information on the specificity and enzyme mechanism of the family of proteins, the crystal structures of CmaA1, CmaA2, and PcaA were solved to 2-, 2-, and 2.65-A resolution, respectively. All three enzymes have a seven-stranded alpha/beta fold similar to other methyltransferases with the location and interactions with the cofactor S-adenosyl-l-methionine conserved. The structures of the ternary complexes demonstrate the position of the mycolic acid substrate binding site. Close examination of the active site reveals electron density that we believe represents a bicarbonate ion. The structures support the hypothesis that these enzymes catalyze methyl transfer via a carbocation mechanism in which the bicarbonate ion acts as a general base. In addition, comparison of the enzyme structures reveals a possible mechanism for substrate specificity. These structures provide a foundation for rational-drug design, which may lead to the development of new inhibitors effective against persistent bacteria.
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<StructureSection load='1kpi' size='340' side='right'caption='[[1kpi]], [[Resolution|resolution]] 2.65&Aring;' scene=''>
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== Structural highlights ==
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<table><tr><td colspan='2'>[[1kpi]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Mycobacterium_tuberculosis Mycobacterium tuberculosis]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1KPI OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1KPI FirstGlance]. <br>
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</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.65&#8491;</td></tr>
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<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=10A:DIDECYL-DIMETHYL-AMMONIUM'>10A</scene>, <scene name='pdbligand=CO3:CARBONATE+ION'>CO3</scene>, <scene name='pdbligand=SAH:S-ADENOSYL-L-HOMOCYSTEINE'>SAH</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></td></tr>
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<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=1kpi FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1kpi OCA], [https://pdbe.org/1kpi PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1kpi RCSB], [https://www.ebi.ac.uk/pdbsum/1kpi PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1kpi ProSAT], [https://www.topsan.org/Proteins/TBSGC/1kpi TOPSAN]</span></td></tr>
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</table>
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== Function ==
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[https://www.uniprot.org/uniprot/CMAS2_MYCTU CMAS2_MYCTU] Catalyzes the formation of trans cyclopropanated ketomycolate or methoxymycolate through the conversion of a double bond to a cyclopropane ring at the proximal position of an oxygenated mycolic acid via the transfer of a methylene group from S-adenosyl-L-methionine. In the absence of MmaA2, CmaA2 has a non-specific cis-cyclopropanating activity and is able to catalyze the conversion of a double bond to a cis cyclopropane ring at the distal position of an alpha mycolic acid. Cyclopropanated mycolic acids are key factors participating in cell envelope permeability, host immunomodulation and persistence.<ref>PMID:11092877</ref> <ref>PMID:7592990</ref>
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== Evolutionary Conservation ==
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[[Image:Consurf_key_small.gif|200px|right]]
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Check<jmol>
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<jmolCheckbox>
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<scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/kp/1kpi_consurf.spt"</scriptWhenChecked>
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<scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked>
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<text>to colour the structure by Evolutionary Conservation</text>
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</jmolCheckbox>
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</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=1kpi ConSurf].
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<div style="clear:both"></div>
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==About this Structure==
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==See Also==
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1KPI is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Mycobacterium_tuberculosis Mycobacterium tuberculosis] with <scene name='pdbligand=CO3:'>CO3</scene>, <scene name='pdbligand=SO4:'>SO4</scene>, <scene name='pdbligand=SAH:'>SAH</scene> and <scene name='pdbligand=10A:'>10A</scene> as [http://en.wikipedia.org/wiki/ligands ligands]. Active as [http://en.wikipedia.org/wiki/Cyclopropane-fatty-acyl-phospholipid_synthase Cyclopropane-fatty-acyl-phospholipid synthase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.1.1.79 2.1.1.79] Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1KPI OCA].
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*[[Fatty acid synthase 3D structures|Fatty acid synthase 3D structures]]
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== References ==
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==Reference==
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<references/>
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Crystal structures of mycolic acid cyclopropane synthases from Mycobacterium tuberculosis., Huang CC, Smith CV, Glickman MS, Jacobs WR Jr, Sacchettini JC, J Biol Chem. 2002 Mar 29;277(13):11559-69. Epub 2001 Dec 26. PMID:[http://ispc.weizmann.ac.il//pmbin/getpm?pmid=11756461 11756461]
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__TOC__
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[[Category: Cyclopropane-fatty-acyl-phospholipid synthase]]
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</StructureSection>
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[[Category: Large Structures]]
[[Category: Mycobacterium tuberculosis]]
[[Category: Mycobacterium tuberculosis]]
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[[Category: Single protein]]
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[[Category: Glickman MS]]
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[[Category: Glickman, M S.]]
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[[Category: Huang C-C]]
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[[Category: Huang, C C.]]
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[[Category: Jacobs Jr WR]]
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[[Category: Jr., W R.Jacobs.]]
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[[Category: Sacchettini JC]]
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[[Category: Sacchettini, J C.]]
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[[Category: Smith CV]]
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[[Category: Smith, C V.]]
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[[Category: TBSGC, TB Structural Genomics Consortium.]]
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[[Category: 10A]]
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[[Category: CO3]]
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[[Category: SAH]]
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[[Category: SO4]]
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[[Category: mixed alpha beta fold]]
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[[Category: protein structure initiative]]
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[[Category: psi]]
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[[Category: structural genomics]]
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[[Category: tb structural genomics consortium]]
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[[Category: tbsgc]]
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 13:36:34 2008''
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Current revision

Crystal Structure of mycolic acid cyclopropane synthase CmaA2 complexed with SAH and DDDMAB

PDB ID 1kpi

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