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Titolo:
Substrate and inhibitor specificities for human monoamine oxidase A and B are influenced by a single amino acid
Autore:
Geha, RM; Rebrin, I; Chen, K; Shih, JC;
Indirizzi:
Univ So Calif, Sch Pharm, Dept Mol Pharmacol & Toxicol, Los Angeles, CA 90089 USA Univ So Calif Los Angeles CA USA 90089 Toxicol, Los Angeles, CA 90089 USA Univ So Calif, Sch Med, Dept Cell & Neurobiol, Los Angeles, CA 90089 USA Univ So Calif Los Angeles CA USA 90089 urobiol, Los Angeles, CA 90089 USA
Titolo Testata:
JOURNAL OF BIOLOGICAL CHEMISTRY
fascicolo: 13, volume: 276, anno: 2001,
pagine: 9877 - 9882
SICI:
0021-9258(20010330)276:13<9877:SAISFH>2.0.ZU;2-0
Fonte:
ISI
Lingua:
ENG
Soggetto:
SITE-DIRECTED MUTAGENESIS; BEHAVIOR; GENES; SELECTIVITY; FORMS; RAT;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
30
Recensione:
Indirizzi per estratti:
Indirizzo: Shih, JC 1985 Zonal Ave, Los Angeles, CA 90089 USA 1985 Zonal Ave Los Angeles CA USA 90089 os Angeles, CA 90089 USA
Citazione:
R.M. Geha et al., "Substrate and inhibitor specificities for human monoamine oxidase A and B are influenced by a single amino acid", J BIOL CHEM, 276(13), 2001, pp. 9877-9882

Abstract

Monoamine oxidase (MAO) is responsible for the oxidation of biogenic and dietary amines, It exists as two isoforms, A and B, which have a 70% amino acid identity and different substrate and inhibitor specificities. This study reports the identification of residues responsible for conferring this specificity in human MAO A and B, Using site-directed mutagenesis we reciprocally interchanged three pairs of corresponding nonconserved amino acids within the central portion of human MAO. Mutant MAO A-I335Y became like MAO B,which exhibits a higher preference for beta -phenylethylamine than for theMAO A preferred substrate serotonin (5-hydroxytryptamine), and became moresensitive to deprenyl (MAO B-specific inhibitor) than to clorgyline (MAO A-specific inhibitor). The reciprocal mutant MAO B-Y326I exhibited an increased preference for 5-hydroxytryptamine, a decreased preference for beta -phenylethylamine, and, similar to MAO A, was more sensitive to clorgyline than to deprenyl, These mutants also showed a distinct shift in sensitivity for the MAO A- and B-selective inhibitors Ro 41-1049 and Ro 16-6491. Mutant pair MAO A-T245I and MAO B-I236T and mutant pair MAO A-D328G and MAO B-G319Dreduced catalytic activity but did not alter specificity. Our results indicate that Ile-335 in MAO A and Tyr-326 in MAO B play a critical role in determining substrate and inhibitor specificities in human MAO A and B.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 30/03/20 alle ore 19:31:52