1dgg
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HUMAN ERYTHROCYTE CATALSE CYANIDE COMPLEX
OverviewOverview
Human catalase is an heme-containing peroxisomal enzyme that breaks down, hydrogen peroxide to water and oxygen; it is implicated in ethanol, metabolism, inflammation, apoptosis, aging and cancer. The 1. 5 A, resolution human enzyme structure, both with and without bound NADPH, establishes the conserved features of mammalian catalase fold and, assembly, implicates Tyr370 as the tyrosine radical, suggests the, structural basis for redox-sensitive binding of cognate mRNA via the, catalase NADPH binding site, and identifies an unexpectedly substantial, number of water-mediated domain contacts. A molecular ruler mechanism, based on observed water positions in the 25 A-long channel resolves, problems for selecting hydrogen peroxide. Control of water-mediated, hydrogen bonds by this ruler selects for the longer hydrogen peroxide and, explains the paradoxical effects of mutations that increase active site, access but lower catalytic rate. The heme active site is tuned without, compromising peroxide binding through a Tyr-Arg-His-Asp charge relay, arginine residue to heme carboxylate group hydrogen bonding, and aromatic, stacking. Structures of the non-specific cyanide and specific 3-amino-1,2, 4-triazole inhibitor complexes of human catalase identify their modes of, inhibition and help reveal the catalytic mechanism of catalase. Taken, together, these resting state and inhibited human catalase structures, support specific, structure-based mechanisms for the catalase substrate, recognition, reaction and inhibition and provide a molecular basis for, understanding ethanol intoxication and the likely effects of human, polymorphisms.
DiseaseDisease
Known disease associated with this structure: Acatalasemia OMIM:[115500]
About this StructureAbout this Structure
1DGG is a Single protein structure of sequence from Homo sapiens with CYN, HEM and NDP as ligands. Active as Catalase, with EC number 1.11.1.6 Full crystallographic information is available from OCA.
ReferenceReference
Active and inhibited human catalase structures: ligand and NADPH binding and catalytic mechanism., Putnam CD, Arvai AS, Bourne Y, Tainer JA, J Mol Biol. 2000 Feb 11;296(1):295-309. PMID:10656833
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