2qc3: Difference between revisions
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New page: left|200px<br /><applet load="2qc3" size="350" color="white" frame="true" align="right" spinBox="true" caption="2qc3, resolution 2.3Å" /> '''Crystal strucuture of... |
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== | ==Crystal structure of MCAT from Mycobacterium tuberculosis== | ||
The malonyl coenzyme A (CoA)-acyl carrier protein (ACP) transacylase | <StructureSection load='2qc3' size='340' side='right'caption='[[2qc3]], [[Resolution|resolution]] 2.30Å' scene=''> | ||
== Structural highlights == | |||
<table><tr><td colspan='2'>[[2qc3]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Mycobacterium_tuberculosis_H37Rv Mycobacterium tuberculosis H37Rv]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2QC3 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2QC3 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]] 2.3Å</td></tr> | |||
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=ACY:ACETIC+ACID'>ACY</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=2qc3 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2qc3 OCA], [https://pdbe.org/2qc3 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2qc3 RCSB], [https://www.ebi.ac.uk/pdbsum/2qc3 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2qc3 ProSAT]</span></td></tr> | |||
</table> | |||
== Function == | |||
[https://www.uniprot.org/uniprot/FABD_MYCTU FABD_MYCTU] | |||
== 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/qc/2qc3_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=2qc3 ConSurf]. | |||
<div style="clear:both"></div> | |||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
The malonyl coenzyme A (CoA)-acyl carrier protein (ACP) transacylase (MCAT) plays a key role in cell wall biosynthesis in Mycobacterium tuberculosis and other bacteria. The M. tuberculosis MCAT (MtMCAT) is encoded by the FabD gene and catalyzes the transacylation of malonate from malonyl-CoA to holo-ACP. Malonyl-ACP is the substrate in fatty acid biosynthesis and is a by-product of the transacylation reaction. This ability for fatty acid biosynthesis enables M. tuberculosis to survive in hostile environments, and thus understanding the mechanism of biosynthesis is important for the design of new anti-tuberculosis drugs. The 2.3 A crystal structure of MtMCAT reported here shows that its catalytic mechanism differs from those of ScMCAT and EcMCAT, whose structures have previously been determined. In MtMCAT, the C(beta)-O(gamma) bond of Ser91 turns upwards, resulting in a different orientation and thus an overall change of the active pocket compared to other known MCAT enzymes. We identify three new nucleophilic attack chains from the MtMCAT structure: His90-Ser91, Asn155-Wat6-Ser91 and Asn155-His90-Ser91. Enzyme activity assays show that His90A, Asn155A and His90A-Asn155A mutants all have substantially reduced MCAT activity, indicating that M. tuberculosis MCAT supports a unique means of proton transfer. Furthermore, His194 cannot form part of a His-Ser catalytic dyad and only stabilizes the substrate. This new discovery should provide a deeper insight into the catalytic mechanisms of MCATs. | |||
The crystal structure of MCAT from Mycobacterium tuberculosis reveals three new catalytic models.,Li Z, Huang Y, Ge J, Fan H, Zhou X, Li S, Bartlam M, Wang H, Rao Z J Mol Biol. 2007 Aug 24;371(4):1075-83. Epub 2007 Jun 9. PMID:17604051<ref>PMID:17604051</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
</div> | |||
<div class="pdbe-citations 2qc3" style="background-color:#fffaf0;"></div> | |||
[[Category: | == References == | ||
[[Category: | <references/> | ||
[[Category: Bartlam | __TOC__ | ||
[[Category: Ge | </StructureSection> | ||
[[Category: Huang | [[Category: Large Structures]] | ||
[[Category: Li | [[Category: Mycobacterium tuberculosis H37Rv]] | ||
[[Category: Rao | [[Category: Bartlam M]] | ||
[[Category: Wang | [[Category: Ge J]] | ||
[[Category: Huang Y]] | |||
[[Category: Li Z]] | |||
[[Category: Rao Z]] | |||
[[Category: Wang H]] | |||
Latest revision as of 14:28, 30 August 2023
Crystal structure of MCAT from Mycobacterium tuberculosisCrystal structure of MCAT from Mycobacterium tuberculosis
Structural highlights
FunctionEvolutionary Conservation Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf. Publication Abstract from PubMedThe malonyl coenzyme A (CoA)-acyl carrier protein (ACP) transacylase (MCAT) plays a key role in cell wall biosynthesis in Mycobacterium tuberculosis and other bacteria. The M. tuberculosis MCAT (MtMCAT) is encoded by the FabD gene and catalyzes the transacylation of malonate from malonyl-CoA to holo-ACP. Malonyl-ACP is the substrate in fatty acid biosynthesis and is a by-product of the transacylation reaction. This ability for fatty acid biosynthesis enables M. tuberculosis to survive in hostile environments, and thus understanding the mechanism of biosynthesis is important for the design of new anti-tuberculosis drugs. The 2.3 A crystal structure of MtMCAT reported here shows that its catalytic mechanism differs from those of ScMCAT and EcMCAT, whose structures have previously been determined. In MtMCAT, the C(beta)-O(gamma) bond of Ser91 turns upwards, resulting in a different orientation and thus an overall change of the active pocket compared to other known MCAT enzymes. We identify three new nucleophilic attack chains from the MtMCAT structure: His90-Ser91, Asn155-Wat6-Ser91 and Asn155-His90-Ser91. Enzyme activity assays show that His90A, Asn155A and His90A-Asn155A mutants all have substantially reduced MCAT activity, indicating that M. tuberculosis MCAT supports a unique means of proton transfer. Furthermore, His194 cannot form part of a His-Ser catalytic dyad and only stabilizes the substrate. This new discovery should provide a deeper insight into the catalytic mechanisms of MCATs. The crystal structure of MCAT from Mycobacterium tuberculosis reveals three new catalytic models.,Li Z, Huang Y, Ge J, Fan H, Zhou X, Li S, Bartlam M, Wang H, Rao Z J Mol Biol. 2007 Aug 24;371(4):1075-83. Epub 2007 Jun 9. PMID:17604051[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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