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| | ==Crystal structure of human MCD== | | ==Crystal structure of human MCD== |
| - | <StructureSection load='2ygw' size='340' side='right' caption='[[2ygw]], [[Resolution|resolution]] 2.80Å' scene=''> | + | <StructureSection load='2ygw' size='340' side='right'caption='[[2ygw]], [[Resolution|resolution]] 2.80Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[2ygw]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2YGW OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2YGW FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[2ygw]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2YGW OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2YGW FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene>, <scene name='pdbligand=UNX:UNKNOWN+ATOM+OR+ION'>UNX</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]] 2.8Å</td></tr> |
| - | <tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Malonyl-CoA_decarboxylase Malonyl-CoA decarboxylase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=4.1.1.9 4.1.1.9] </span></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='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=2ygw FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2ygw OCA], [http://www.rcsb.org/pdb/explore.do?structureId=2ygw RCSB], [http://www.ebi.ac.uk/pdbsum/2ygw PDBsum]</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=2ygw FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2ygw OCA], [https://pdbe.org/2ygw PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2ygw RCSB], [https://www.ebi.ac.uk/pdbsum/2ygw PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2ygw ProSAT]</span></td></tr> |
| | </table> | | </table> |
| | == Disease == | | == Disease == |
| - | [[http://www.uniprot.org/uniprot/DCMC_HUMAN DCMC_HUMAN]] Malonic aciduria. Defects in MLYCD are the cause of malonyl-CoA decarboxylase deficiency (MLYCD deficiency) [MIM:[http://omim.org/entry/248360 248360]]. MLYCD deficiency is an autosomal recessive disease characterized by abdominal pain, chronic constipation, episodic vomiting, metabolic acidosis and malonic aciduria. | + | [https://www.uniprot.org/uniprot/DCMC_HUMAN DCMC_HUMAN] Malonic aciduria. Defects in MLYCD are the cause of malonyl-CoA decarboxylase deficiency (MLYCD deficiency) [MIM:[https://omim.org/entry/248360 248360]. MLYCD deficiency is an autosomal recessive disease characterized by abdominal pain, chronic constipation, episodic vomiting, metabolic acidosis and malonic aciduria. |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/DCMC_HUMAN DCMC_HUMAN]] Catalyzes the conversion of malonyl-CoA to acetyl-CoA. In the fatty acid biosynthesis MCD selectively removes malonyl-CoA and thus assures that methyl-malonyl-CoA is the only chain elongating substrate for fatty acid synthase and that fatty acids with multiple methyl side chains are produced. In peroxisomes it may be involved in degrading intraperoxisomal malonyl-CoA, which is generated by the peroxisomal beta-oxidation of odd chain-length dicarboxylic fatty acids. | + | [https://www.uniprot.org/uniprot/DCMC_HUMAN DCMC_HUMAN] Catalyzes the conversion of malonyl-CoA to acetyl-CoA. In the fatty acid biosynthesis MCD selectively removes malonyl-CoA and thus assures that methyl-malonyl-CoA is the only chain elongating substrate for fatty acid synthase and that fatty acids with multiple methyl side chains are produced. In peroxisomes it may be involved in degrading intraperoxisomal malonyl-CoA, which is generated by the peroxisomal beta-oxidation of odd chain-length dicarboxylic fatty acids. |
| | <div style="background-color:#fffaf0;"> | | <div style="background-color:#fffaf0;"> |
| | == Publication Abstract from PubMed == | | == Publication Abstract from PubMed == |
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| | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> |
| | </div> | | </div> |
| | + | <div class="pdbe-citations 2ygw" style="background-color:#fffaf0;"></div> |
| | == References == | | == References == |
| | <references/> | | <references/> |
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| | </StructureSection> | | </StructureSection> |
| | [[Category: Homo sapiens]] | | [[Category: Homo sapiens]] |
| - | [[Category: Malonyl-CoA decarboxylase]] | + | [[Category: Large Structures]] |
| - | [[Category: Allerston, C]] | + | [[Category: Allerston C]] |
| - | [[Category: Arrowsmith, C H]] | + | [[Category: Arrowsmith CH]] |
| - | [[Category: Bountra, C]] | + | [[Category: Bountra C]] |
| - | [[Category: Chaikuad, A]] | + | [[Category: Chaikuad A]] |
| - | [[Category: Delft, F Von]]
| + | [[Category: Edwards A]] |
| - | [[Category: Edwards, A]] | + | [[Category: Gileadi O]] |
| - | [[Category: Gileadi, O]] | + | [[Category: Kavanagh K]] |
| - | [[Category: Kavanagh, K]] | + | [[Category: Krojer T]] |
| - | [[Category: Krojer, T]] | + | [[Category: Oppermann U]] |
| - | [[Category: Oppermann, U]] | + | [[Category: Puranik S]] |
| - | [[Category: Puranik, S]] | + | [[Category: Savitsky P]] |
| - | [[Category: Savitsky, P]] | + | [[Category: Vollmar M]] |
| - | [[Category: Vollmar, M]] | + | [[Category: Weigelt J]] |
| - | [[Category: Weigelt, J]] | + | [[Category: Yue WW]] |
| - | [[Category: Yue, W W]] | + | [[Category: Von Delft F]] |
| - | [[Category: Lyase]] | + | |
| Structural highlights
Disease
DCMC_HUMAN Malonic aciduria. Defects in MLYCD are the cause of malonyl-CoA decarboxylase deficiency (MLYCD deficiency) [MIM:248360. MLYCD deficiency is an autosomal recessive disease characterized by abdominal pain, chronic constipation, episodic vomiting, metabolic acidosis and malonic aciduria.
Function
DCMC_HUMAN Catalyzes the conversion of malonyl-CoA to acetyl-CoA. In the fatty acid biosynthesis MCD selectively removes malonyl-CoA and thus assures that methyl-malonyl-CoA is the only chain elongating substrate for fatty acid synthase and that fatty acids with multiple methyl side chains are produced. In peroxisomes it may be involved in degrading intraperoxisomal malonyl-CoA, which is generated by the peroxisomal beta-oxidation of odd chain-length dicarboxylic fatty acids.
Publication Abstract from PubMed
Malonyl-coenzyme A decarboxylase (MCD) is found from bacteria to humans, has important roles in regulating fatty acid metabolism and food intake, and is an attractive target for drug discovery. We report here four crystal structures of MCD from human, Rhodopseudomonas palustris, Agrobacterium vitis, and Cupriavidus metallidurans at up to 2.3 A resolution. The MCD monomer contains an N-terminal helical domain involved in oligomerization and a C-terminal catalytic domain. The four structures exhibit substantial differences in the organization of the helical domains and, consequently, the oligomeric states and intersubunit interfaces. Unexpectedly, the MCD catalytic domain is structurally homologous to those of the GCN5-related N-acetyltransferase superfamily, especially the curacin A polyketide synthase catalytic module, with a conserved His-Ser/Thr dyad important for catalysis. Our structures, along with mutagenesis and kinetic studies, provide a molecular basis for understanding pathogenic mutations and catalysis, as well as a template for structure-based drug design.
Crystal structures of malonyl-coenzyme a decarboxylase provide insights into its catalytic mechanism and disease-causing mutations.,Froese DS, Forouhar F, Tran TH, Vollmar M, Kim YS, Lew S, Neely H, Seetharaman J, Shen Y, Xiao R, Acton TB, Everett JK, Cannone G, Puranik S, Savitsky P, Krojer T, Pilka ES, Kiyani W, Lee WH, Marsden BD, von Delft F, Allerston CK, Spagnolo L, Gileadi O, Montelione GT, Oppermann U, Yue WW, Tong L Structure. 2013 Jul 2;21(7):1182-92. doi: 10.1016/j.str.2013.05.001. Epub 2013, Jun 20. PMID:23791943[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Froese DS, Forouhar F, Tran TH, Vollmar M, Kim YS, Lew S, Neely H, Seetharaman J, Shen Y, Xiao R, Acton TB, Everett JK, Cannone G, Puranik S, Savitsky P, Krojer T, Pilka ES, Kiyani W, Lee WH, Marsden BD, von Delft F, Allerston CK, Spagnolo L, Gileadi O, Montelione GT, Oppermann U, Yue WW, Tong L. Crystal structures of malonyl-coenzyme a decarboxylase provide insights into its catalytic mechanism and disease-causing mutations. Structure. 2013 Jul 2;21(7):1182-92. doi: 10.1016/j.str.2013.05.001. Epub 2013, Jun 20. PMID:23791943 doi:10.1016/j.str.2013.05.001
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