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| | ==2.0 Angstroms X-ray crystal structure of human 2-amino-3-carboxymuconate-6-semialdehye decarboxylase== | | ==2.0 Angstroms X-ray crystal structure of human 2-amino-3-carboxymuconate-6-semialdehye decarboxylase== |
| - | <StructureSection load='4ofc' size='340' side='right' caption='[[4ofc]], [[Resolution|resolution]] 1.99Å' scene=''> | + | <StructureSection load='4ofc' size='340' side='right'caption='[[4ofc]], [[Resolution|resolution]] 1.99Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[4ofc]] is a 6 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4OFC OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4OFC FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[4ofc]] is a 6 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=4OFC OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4OFC FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=ZN:ZINC+ION'>ZN</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]] 1.99Å</td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">ACMSD ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr>
| + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr> |
| - | <tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Aminocarboxymuconate-semialdehyde_decarboxylase Aminocarboxymuconate-semialdehyde decarboxylase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=4.1.1.45 4.1.1.45] </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=4ofc FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4ofc OCA], [https://pdbe.org/4ofc PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4ofc RCSB], [https://www.ebi.ac.uk/pdbsum/4ofc PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4ofc 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=4ofc FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4ofc OCA], [http://pdbe.org/4ofc PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4ofc RCSB], [http://www.ebi.ac.uk/pdbsum/4ofc PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4ofc ProSAT]</span></td></tr> | + | |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/ACMSD_HUMAN ACMSD_HUMAN]] Converts alpha-amino-beta-carboxymuconate-epsilon-semialdehyde (ACMS) to alpha-aminomuconate semialdehyde (AMS). ACMS can be converted non-enzymatically to quinolate (QA), a key precursor of NAD, and a potent endogenous excitotoxin of neuronal cells which is implicated in the pathogenesis of various neurodegenerative disorders. In the presence of ACMSD, ACMS is converted to AMS, a benign catabolite. ACMSD ultimately controls the metabolic fate of tryptophan catabolism along the kynurenine pathway.<ref>PMID:19843166</ref> <ref>PMID:12140278</ref> | + | [https://www.uniprot.org/uniprot/ACMSD_HUMAN ACMSD_HUMAN] Converts alpha-amino-beta-carboxymuconate-epsilon-semialdehyde (ACMS) to alpha-aminomuconate semialdehyde (AMS). ACMS can be converted non-enzymatically to quinolate (QA), a key precursor of NAD, and a potent endogenous excitotoxin of neuronal cells which is implicated in the pathogenesis of various neurodegenerative disorders. In the presence of ACMSD, ACMS is converted to AMS, a benign catabolite. ACMSD ultimately controls the metabolic fate of tryptophan catabolism along the kynurenine pathway.<ref>PMID:19843166</ref> <ref>PMID:12140278</ref> |
| | <div style="background-color:#fffaf0;"> | | <div style="background-color:#fffaf0;"> |
| | == Publication Abstract from PubMed == | | == Publication Abstract from PubMed == |
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| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Aminocarboxymuconate-semialdehyde decarboxylase]] | + | [[Category: Homo sapiens]] |
| - | [[Category: Human]] | + | [[Category: Large Structures]] |
| - | [[Category: Chen, L]] | + | [[Category: Chen L]] |
| - | [[Category: Hasegawa, Y]] | + | [[Category: Hasegawa Y]] |
| - | [[Category: Huo, L]] | + | [[Category: Huo L]] |
| - | [[Category: Iwaki, H]] | + | [[Category: Iwaki H]] |
| - | [[Category: Liu, A]] | + | [[Category: Liu A]] |
| - | [[Category: Liu, F]] | + | [[Category: Liu F]] |
| - | [[Category: Decarboxylase]]
| + | |
| - | [[Category: Oxidoreductase]]
| + | |
| - | [[Category: Tim-barrel]]
| + | |
| Structural highlights
Function
ACMSD_HUMAN Converts alpha-amino-beta-carboxymuconate-epsilon-semialdehyde (ACMS) to alpha-aminomuconate semialdehyde (AMS). ACMS can be converted non-enzymatically to quinolate (QA), a key precursor of NAD, and a potent endogenous excitotoxin of neuronal cells which is implicated in the pathogenesis of various neurodegenerative disorders. In the presence of ACMSD, ACMS is converted to AMS, a benign catabolite. ACMSD ultimately controls the metabolic fate of tryptophan catabolism along the kynurenine pathway.[1] [2]
Publication Abstract from PubMed
Human alpha-amino-beta-carboxymuconate-epsilon-semialdehyde decarboxylase determines the fate of tryptophan metabolites in the kynurenine pathway by controlling the quinolinate levels for de novo nicotinamide adenine dinucleotide biosynthesis. The unstable nature of its substrate has made gaining insight into its reaction mechanism difficult. Our electron paramagnetic resonance (EPR) spectroscopic study on the Cu-substituted human enzyme suggests that the native substrate does not directly ligate to the metal ion. Substrate binding did not result in a change of either the hyperfine structure or the super-hyperfine structure of the EPR spectrum. We also determined the crystal structure of the human enzyme in its native catalytically active state (at 1.99 A resolution), a substrate analogue-bound form (2.50 A resolution), and a selected active site mutant form with one of the putative substrate binding residues altered (2.32 A resolution). These structures illustrate that each asymmetric unit contains three pairs of dimers. Consistent with the EPR findings, the ligand-bound complex structure shows that the substrate analogue does not directly coordinate to the metal ion but is bound to the active site by two arginine residues through noncovalent interactions. Proteins 2014; (c) 2014 Wiley Periodicals, Inc.
Human alpha-amino-beta-carboxymuconate-epsilon-semialdehyde decarboxylase (ACMSD): A structural and mechanistic unveiling.,Huo L, Liu F, Iwaki H, Li T, Hasegawa Y, Liu A Proteins. 2014 Nov 12. doi: 10.1002/prot.24722. PMID:25392945[3]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Garavaglia S, Perozzi S, Galeazzi L, Raffaelli N, Rizzi M. The crystal structure of human alpha-amino-beta-carboxymuconate-epsilon-semialdehyde decarboxylase in complex with 1,3-dihydroxyacetonephosphate suggests a regulatory link between NAD synthesis and glycolysis. FEBS J. 2009 Nov;276(22):6615-23. Epub 2009 Oct 16. PMID:19843166 doi:10.1111/j.1742-4658.2009.07372.x
- ↑ Fukuoka S, Ishiguro K, Yanagihara K, Tanabe A, Egashira Y, Sanada H, Shibata K. Identification and expression of a cDNA encoding human alpha-amino-beta-carboxymuconate-epsilon-semialdehyde decarboxylase (ACMSD). A key enzyme for the tryptophan-niacine pathway and "quinolinate hypothesis". J Biol Chem. 2002 Sep 20;277(38):35162-7. Epub 2002 Jul 24. PMID:12140278 doi:http://dx.doi.org/10.1074/jbc.M200819200
- ↑ Huo L, Liu F, Iwaki H, Li T, Hasegawa Y, Liu A. Human alpha-amino-beta-carboxymuconate-epsilon-semialdehyde decarboxylase (ACMSD): A structural and mechanistic unveiling. Proteins. 2014 Nov 12. doi: 10.1002/prot.24722. PMID:25392945 doi:http://dx.doi.org/10.1002/prot.24722
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