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Titolo:
Crystal structure of the tumor-promoter okadaic acid bound to protein phosphatase-1
Autore:
Maynes, JT; Bateman, KS; Cherney, MM; Das, AK; Luu, HA; Holmes, CFB; James, MNG;
Indirizzi:
Univ Alberta, Fac Med, Dept Biochem, Grp Prot Struct & Funct,Canadian InstHlth Res, Edmonton, AB T6G 2H7, Canada Univ Alberta Edmonton AB Canada T6G2H7 Res, Edmonton, AB T6G 2H7, Canada Indian Inst Technol, Dept Biotechnol, Kharagpur 721302, W Bengal, India Indian Inst Technol Kharagpur W Bengal India 721302 1302, W Bengal, India
Titolo Testata:
JOURNAL OF BIOLOGICAL CHEMISTRY
fascicolo: 47, volume: 276, anno: 2001,
pagine: 44078 - 44082
SICI:
0021-9258(20011123)276:47<44078:CSOTTO>2.0.ZU;2-R
Fonte:
ISI
Lingua:
ENG
Soggetto:
NATURAL PRODUCT INHIBITORS; SER-THR PHOSPHATASES; CATALYTIC SUBUNIT; CELLULAR-REGULATION; SPONGE TOXIN; CALYCULIN-A; BINDING; COMPLEX; MODEL; PP2A;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
36
Recensione:
Indirizzi per estratti:
Indirizzo: James, MNG Univ Alberta, Fac Med, Dept Biochem, Grp Prot Struct & Funct,Canadian InstHlth Res, Edmonton, AB T6G 2H7, Canada Univ Alberta Edmonton ABCanada T6G 2H7 on, AB T6G 2H7, Canada
Citazione:
J.T. Maynes et al., "Crystal structure of the tumor-promoter okadaic acid bound to protein phosphatase-1", J BIOL CHEM, 276(47), 2001, pp. 44078-44082

Abstract

Protein phosphatase-1 (PP1) plays a key role in dephosphorylation in numerous biological processes such as glycogen metabolism, cell cycle regulation, smooth muscle contract-ion, and protein synthesis. Microorganisms producea variety of inhibitors of PP1, which include the microcystin class of inhibitors and okadaic acid, the latter being the major cause of diarrhetic shellfish poisoning and a powerful tumor promoter. We have determined the crystal structure of the molecular complex of okadaic acid bound to PPI to a resolution of 1.9 Angstrom. This structure reveals that the acid binds in a hydrophobic groove adjacent to the active site of the protein and interactswith basic residues within the active site. Okadaic acid exhibits a cyclicstructure, which is maintained via an intramolecular hydrogen bond. This is reminiscent of other macrocyclic protein phosphatase inhibitors. The inhibitor-bound enzyme shows very little conformational change when compared with two other PPI structures, except in the inhibitor-sensitive beta 12-beta13 loop region. The selectivity of okadaic acid for protein phosphatases-1and -2A but not PP-2B (calcineurin) may be reassessed in light of this study.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 28/03/20 alle ore 14:07:24