2a7s: Difference between revisions

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==Crystal Structure of the Acyl-CoA Carboxylase, AccD5, from Mycobacterium tuberculosis==
==Crystal Structure of the Acyl-CoA Carboxylase, AccD5, from Mycobacterium tuberculosis==
<StructureSection load='2a7s' size='340' side='right' caption='[[2a7s]], [[Resolution|resolution]] 2.90&Aring;' scene=''>
<StructureSection load='2a7s' size='340' side='right'caption='[[2a7s]], [[Resolution|resolution]] 2.90&Aring;' scene=''>
== Structural highlights ==
== Structural highlights ==
<table><tr><td colspan='2'>[[2a7s]] is a 6 chain structure with sequence from [http://en.wikipedia.org/wiki/"bacillus_tuberculosis"_(zopf_1883)_klein_1884 "bacillus tuberculosis" (zopf 1883) klein 1884]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2A7S OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2A7S FirstGlance]. <br>
<table><tr><td colspan='2'>[[2a7s]] is a 6 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=2A7S OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2A7S FirstGlance]. <br>
</td></tr><tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">accD5, pccB ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=1773 "Bacillus tuberculosis" (Zopf 1883) Klein 1884])</td></tr>
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.9&#8491;</td></tr>
<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Propionyl-CoA_carboxylase Propionyl-CoA carboxylase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=6.4.1.3 6.4.1.3] </span></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=2a7s FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2a7s OCA], [https://pdbe.org/2a7s PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2a7s RCSB], [https://www.ebi.ac.uk/pdbsum/2a7s PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2a7s ProSAT]</span></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=2a7s FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2a7s OCA], [http://pdbe.org/2a7s PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=2a7s RCSB], [http://www.ebi.ac.uk/pdbsum/2a7s PDBsum]</span></td></tr>
</table>
</table>
== Function ==
[https://www.uniprot.org/uniprot/ACCD5_MYCTU ACCD5_MYCTU] Component of a biotin-dependent acyl-CoA carboxylase complex. This subunit transfers the CO2 from carboxybiotin to the CoA ester substrate (PubMed:16354663, PubMed:16385038, PubMed:28222482). When associated with the alpha3 subunit AccA3, is involved in the carboxylation of acetyl-CoA and propionyl-CoA, with a preference for propionyl-CoA (PubMed:16354663, PubMed:16385038, PubMed:28222482). Is also required for the activity of the long-chain acyl-CoA carboxylase (LCC) complex (PubMed:28222482).<ref>PMID:16354663</ref> <ref>PMID:16385038</ref> <ref>PMID:28222482</ref>
== Evolutionary Conservation ==
== Evolutionary Conservation ==
[[Image:Consurf_key_small.gif|200px|right]]
[[Image:Consurf_key_small.gif|200px|right]]
Check<jmol>
Check<jmol>
   <jmolCheckbox>
   <jmolCheckbox>
     <scriptWhenChecked>select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/a7/2a7s_consurf.spt"</scriptWhenChecked>
     <scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/a7/2a7s_consurf.spt"</scriptWhenChecked>
     <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked>
     <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked>
     <text>to colour the structure by Evolutionary Conservation</text>
     <text>to colour the structure by Evolutionary Conservation</text>
   </jmolCheckbox>
   </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].
</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=2a7s ConSurf].
<div style="clear:both"></div>
<div style="clear:both"></div>
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
Mycolic acids and multimethyl-branched fatty acids are found uniquely in the cell envelope of pathogenic mycobacteria. These unusually long fatty acids are essential for the survival, virulence, and antibiotic resistance of Mycobacterium tuberculosis. Acyl-CoA carboxylases (ACCases) commit acyl-CoAs to the biosynthesis of these unique fatty acids. Unlike other organisms such as Escherichia coli or humans that have only one or two ACCases, M. tuberculosis contains six ACCase carboxyltransferase domains, AccD1-6, whose specific roles in the pathogen are not well defined. Previous studies indicate that AccD4, AccD5, and AccD6 are important for cell envelope lipid biosynthesis and that its disruption leads to pathogen death. We have determined the 2.9-Angstroms crystal structure of AccD5, whose sequence, structure, and active site are highly conserved with respect to the carboxyltransferase domain of the Streptomyces coelicolor propionyl-CoA carboxylase. Contrary to the previous proposal that AccD4-5 accept long-chain acyl-CoAs as their substrates, both crystal structure and kinetic assay indicate that AccD5 prefers propionyl-CoA as its substrate and produces methylmalonyl-CoA, the substrate for the biosyntheses of multimethyl-branched fatty acids such as mycocerosic, phthioceranic, hydroxyphthioceranic, mycosanoic, and mycolipenic acids. Extensive in silico screening of National Cancer Institute compounds and the University of California, Irvine, ChemDB database resulted in the identification of one inhibitor with a K(i) of 13.1 microM. Our results pave the way toward understanding the biological roles of key ACCases that commit acyl-CoAs to the biosynthesis of cell envelope fatty acids, in addition to providing a target for structure-based development of antituberculosis therapeutics.
Structure-based inhibitor design of AccD5, an essential acyl-CoA carboxylase carboxyltransferase domain of Mycobacterium tuberculosis.,Lin TW, Melgar MM, Kurth D, Swamidass SJ, Purdon J, Tseng T, Gago G, Baldi P, Gramajo H, Tsai SC Proc Natl Acad Sci U S A. 2006 Feb 28;103(9):3072-7. Epub 2006 Feb 21. PMID:16492739<ref>PMID:16492739</ref>
From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 2a7s" style="background-color:#fffaf0;"></div>
== References ==
== References ==
<references/>
<references/>
__TOC__
__TOC__
</StructureSection>
</StructureSection>
[[Category: Propionyl-CoA carboxylase]]
[[Category: Large Structures]]
[[Category: Lin, T]]
[[Category: Mycobacterium tuberculosis]]
[[Category: Melgar, M]]
[[Category: Lin T]]
[[Category: Purdon, J]]
[[Category: Melgar M]]
[[Category: Tsai, S C]]
[[Category: Purdon J]]
[[Category: Tseng, T]]
[[Category: Tsai SC]]
[[Category: Acetyl-coa carboxylase]]
[[Category: Tseng T]]
[[Category: Acyl-coa carboxylase]]
[[Category: Carboxylase]]
[[Category: Carboxyltransferase]]
[[Category: Fatty acid]]
[[Category: Ligase]]
[[Category: Mycolic acid]]
[[Category: Polyketide]]
[[Category: Propionyl-coa carboxylase]]

Latest revision as of 12:11, 14 February 2024

Crystal Structure of the Acyl-CoA Carboxylase, AccD5, from Mycobacterium tuberculosisCrystal Structure of the Acyl-CoA Carboxylase, AccD5, from Mycobacterium tuberculosis

Structural highlights

2a7s is a 6 chain structure with sequence from Mycobacterium tuberculosis. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:X-ray diffraction, Resolution 2.9Å
Resources:FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

ACCD5_MYCTU Component of a biotin-dependent acyl-CoA carboxylase complex. This subunit transfers the CO2 from carboxybiotin to the CoA ester substrate (PubMed:16354663, PubMed:16385038, PubMed:28222482). When associated with the alpha3 subunit AccA3, is involved in the carboxylation of acetyl-CoA and propionyl-CoA, with a preference for propionyl-CoA (PubMed:16354663, PubMed:16385038, PubMed:28222482). Is also required for the activity of the long-chain acyl-CoA carboxylase (LCC) complex (PubMed:28222482).[1] [2] [3]

Evolutionary Conservation

Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.

References

  1. ↑ Oh TJ, Daniel J, Kim HJ, Sirakova TD, Kolattukudy PE. Identification and characterization of Rv3281 as a novel subunit of a biotin-dependent acyl-CoA Carboxylase in Mycobacterium tuberculosis H37Rv. J Biol Chem. 2006 Feb 17;281(7):3899-908. PMID:16354663 doi:10.1074/jbc.M511761200
  2. ↑ Gago G, Kurth D, Diacovich L, Tsai SC, Gramajo H. Biochemical and structural characterization of an essential acyl coenzyme A carboxylase from Mycobacterium tuberculosis. J Bacteriol. 2006 Jan;188(2):477-86. PMID:16385038 doi:10.1128/JB.188.2.477-486.2006
  3. ↑ Bazet Lyonnet B, Diacovich L, Gago G, Spina L, Bardou F, Lemassu A, Quémard A, Gramajo H. Functional reconstitution of the Mycobacterium tuberculosis long-chain acyl-CoA carboxylase from multiple acyl-CoA subunits. FEBS J. 2017 Apr;284(7):1110-1125. PMID:28222482 doi:10.1111/febs.14046

2a7s, resolution 2.90Å

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