4ign

2.32 Angstrom X-ray Crystal structure of R47A mutant of human ACMSD

spinqualitylabelsall models 4ign, resolution 2.33Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 4ign is a 6 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Ligands: ZN Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT 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. 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 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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