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Titolo:
CRYSTAL-STRUCTURE OF A EUKARYOTIC (PEA SEEDLING) COPPER-CONTAINING AMINE OXIDASE AT 2.2-ANGSTROM RESOLUTION
Autore:
KUMAR V; DOOLEY DM; FREEMAN HC; GUSS JM; HARVEY I; MCGUIRL MA; WILCE MCJ; ZUBAK VM;
Indirizzi:
UNIV SYDNEY,SCH CHEM SYDNEY NSW 2006 AUSTRALIA UNIV SYDNEY,SCH CHEM SYDNEY NSW 2006 AUSTRALIA MONTANA STATE UNIV,DEPT CHEM & BIOCHEM BOZEMAN MT 59717 UNIV SYDNEY,DEPT BIOCHEM SYDNEY NSW 2006 AUSTRALIA
Titolo Testata:
Structure
fascicolo: 8, volume: 4, anno: 1996,
pagine: 943 - 955
SICI:
0969-2126(1996)4:8<943:COAE(S>2.0.ZU;2-2
Fonte:
ISI
Lingua:
ENG
Soggetto:
DIAMINE OXIDASE; ACTIVE-SITE; COORDINATION CHEMISTRY; SULFHYDRYL-GROUPS; TOPA QUINONE; PROTEIN; SUBSTRATE; MECHANISM; CRYSTALLIZATION; PURIFICATION;
Keywords:
AMINE OXIDASE; COPPER PROTEIN; CRYSTAL STRUCTURE; TOPA QUINONE;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Science Citation Index Expanded
Science Citation Index Expanded
Citazioni:
51
Recensione:
Indirizzi per estratti:
Citazione:
V. Kumar et al., "CRYSTAL-STRUCTURE OF A EUKARYOTIC (PEA SEEDLING) COPPER-CONTAINING AMINE OXIDASE AT 2.2-ANGSTROM RESOLUTION", Structure, 4(8), 1996, pp. 943-955

Abstract

Background: Copper-containing amine oxidases catalyze the oxidative deamination of primary amines to aldehydes, in a reaction that requiresfree radicals. These enzymes are important in many biological processes, including cell differentiation and growth, wound healing, detoxification and signalling. The catalytic reaction requires a redox cofactor, topa quinone (TPQ), which is derived by post-translational modification of an invariant tyrosine residue. Both the biogenesis of the TPQ cofactor and the reaction catalyzed by the enzyme require the presenceof a copper atom at the active site. The crystal structure of a prokaryotic copper amine oxidase from E. coli (ECAO) has recently been reported. Results: The first structure of a eukaryotic (pea seedling) amine oxidase (PSAO) has been solved and refined at 2.2 Angstrom resolution. The crystallographic phases were derived from a single phosphotungstic acid derivative. The positions of the tungsten atoms in the W-12 clusters were obtained by molecular replacement using E. coli amine oxidase as a search model. The methodology avoided bias from the search model, and provides an essentially independent view of a eukaryotic amine oxidase. The PSAO molecule is a homodimer; each subunit has three domains, The active site of each subunil: lies near an edge of the beta-sandwich of the largest domain, but is not accessible from the solvent. The essential active-site copper atom is coordinated by three histidine side chains and two water molecules in an approximately square-pyramidal arrangement, All the atoms of the TPQ cofactor are unambiguously defined, the shortest distance to the copper atom being similar to 6 Angstrom. Conclusions: There is considerable structural homology between PSAO and ECAO, A combination of evidence from both structures indicates that the TPQ side chain is sufficiently flexible to permit the aromatic group to rotate about the C beta-C gamma bond, and to move between bonding and non-bonding positions with respect to the Cu atom. Conformational flexibility is also required at the surface of the molecule to allow the substrates access to the active site, which is inaccessible to solvent, as expected for an enzyme that uses radical chemistry.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 26/11/20 alle ore 20:25:13