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| | <StructureSection load='7agp' size='340' side='right'caption='[[7agp]], [[Resolution|resolution]] 2.40Å' scene=''> | | <StructureSection load='7agp' size='340' side='right'caption='[[7agp]], [[Resolution|resolution]] 2.40Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[7agp]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Mycbo Mycbo]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7AGP OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=7AGP FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[7agp]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Mycobacterium_tuberculosis_variant_bovis_AF2122/97 Mycobacterium tuberculosis variant bovis AF2122/97]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7AGP OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7AGP FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene></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]] 2.4Å</td></tr> |
| - | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat"><div style='overflow: auto; max-height: 3em;'>[[7agq|7agq]], [[7agr|7agr]], [[7ags|7ags]], [[7agt|7agt]], [[7agu|7agu]]</div></td></tr>
| + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene></td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">mas, BQ2027_MB2965C ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=233413 MYCBO])</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=7agp FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7agp OCA], [https://pdbe.org/7agp PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7agp RCSB], [https://www.ebi.ac.uk/pdbsum/7agp PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7agp ProSAT]</span></td></tr> |
| - | <tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Mycocerosate_synthase Mycocerosate synthase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.3.1.111 2.3.1.111] </span></td></tr>
| + | |
| - | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://proteopedia.org/fgij/fg.htm?mol=7agp FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7agp OCA], [http://pdbe.org/7agp PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=7agp RCSB], [http://www.ebi.ac.uk/pdbsum/7agp PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=7agp ProSAT]</span></td></tr> | + | |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/MCAS_MYCBO MCAS_MYCBO]] Catalyzes the elongation of long-chain fatty acyl-CoA with 3 or 4 methylmalonyl-CoA (not malonyl-CoA) as the elongating agent to form tri- or tetramethylated-branched fatty acids known as mycocerosyl lipids.<ref>PMID:3880746</ref> | + | [https://www.uniprot.org/uniprot/MCAS_MYCBO MCAS_MYCBO] Catalyzes the elongation of long-chain fatty acyl-CoA with 3 or 4 methylmalonyl-CoA (not malonyl-CoA) as the elongating agent to form tri- or tetramethylated-branched fatty acids known as mycocerosyl lipids.<ref>PMID:3880746</ref> |
| | <div style="background-color:#fffaf0;"> | | <div style="background-color:#fffaf0;"> |
| | == Publication Abstract from PubMed == | | == Publication Abstract from PubMed == |
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| | </StructureSection> | | </StructureSection> |
| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| - | [[Category: Mycbo]] | + | [[Category: Mycobacterium tuberculosis variant bovis AF2122/97]] |
| - | [[Category: Mycocerosate synthase]]
| + | [[Category: Brison Y]] |
| - | [[Category: Brison, Y]] | + | [[Category: Maveyraud L]] |
| - | [[Category: Maveyraud, L]] | + | [[Category: Mourey L]] |
| - | [[Category: Mourey, L]] | + | [[Category: Nahoum V]] |
| - | [[Category: Nahoum, V]] | + | |
| - | [[Category: Acyltransferase domain]]
| + | |
| - | [[Category: Mycobacterium tuberculosis]]
| + | |
| - | [[Category: Mycocerosic acid synthase]]
| + | |
| - | [[Category: Polyketide synthase]]
| + | |
| - | [[Category: Transferase]]
| + | |
| Structural highlights
Function
MCAS_MYCBO Catalyzes the elongation of long-chain fatty acyl-CoA with 3 or 4 methylmalonyl-CoA (not malonyl-CoA) as the elongating agent to form tri- or tetramethylated-branched fatty acids known as mycocerosyl lipids.[1]
Publication Abstract from PubMed
Mycobacterium tuberculosis is the causative agent of the tuberculosis disease, which claims more human lives each year than any other bacterial pathogen. M. tuberculosis and other mycobacterial pathogens have developed a range of unique features that enhance their virulence and promote their survival in the human host. Among these features lies the particular cell envelope with high lipid content, which plays a substantial role in mycobacterial pathogenicity. Several envelope components of M. tuberculosis and other mycobacteria, e.g., mycolic acids, phthiocerol dimycocerosates, and phenolic glycolipids, belong to the "family" of polyketides, secondary metabolites synthesized by fascinating versatile enzymes-polyketide synthases. These megasynthases consist of multiple catalytic domains, among which the acyltransferase domain plays a key role in selecting and transferring the substrates required for polyketide extension. Here, we present three new crystal structures of acyltransferase domains of mycobacterial polyketide synthases and, for one of them, provide evidence for the identification of residues determining extender unit specificity. Unravelling the molecular basis for such specificity is of high importance considering the role played by extender units for the final structure of key mycobacterial components. This work provides major advances for the use of mycobacterial polyketide synthases as potential therapeutic targets and, more generally, contributes to the prediction and bioengineering of polyketide synthases with desired specificity.
Molecular Basis for Extender Unit Specificity of Mycobacterial Polyketide Synthases.,Grabowska AD, Brison Y, Maveyraud L, Gavalda S, Faille A, Nahoum V, Bon C, Guilhot C, Pedelacq JD, Chalut C, Mourey L ACS Chem Biol. 2020 Nov 25. doi: 10.1021/acschembio.0c00772. PMID:33237724[2]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Rainwater DL, Kolattukudy PE. Fatty acid biosynthesis in Mycobacterium tuberculosis var. bovis Bacillus Calmette-Guerin. Purification and characterization of a novel fatty acid synthase, mycocerosic acid synthase, which elongates n-fatty acyl-CoA with methylmalonyl-CoA. J Biol Chem. 1985 Jan 10;260(1):616-23. PMID:3880746
- ↑ Grabowska AD, Brison Y, Maveyraud L, Gavalda S, Faille A, Nahoum V, Bon C, Guilhot C, Pedelacq JD, Chalut C, Mourey L. Molecular Basis for Extender Unit Specificity of Mycobacterial Polyketide Synthases. ACS Chem Biol. 2020 Nov 25. doi: 10.1021/acschembio.0c00772. PMID:33237724 doi:http://dx.doi.org/10.1021/acschembio.0c00772
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