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Titolo:
Computational studies of the domain movement and the catalytic mechanism of thymidine phosphorylase
Autore:
Rick, SW; Abashkin, YG; Hilderbrandt, RL; Burt, SK;
Indirizzi:
NCI, Adv Biomed Comp Ctr, Frederick Canc Res & Dev Ctr, SAIC Frederick, Frederick, MD 21702 USA NCI Frederick MD USA 21702 v Ctr, SAIC Frederick, Frederick, MD 21702 USA Natl Sci Fdn, Div Chem, Arlington, VA 22230 USA Natl Sci Fdn Arlington VAUSA 22230 dn, Div Chem, Arlington, VA 22230 USA
Titolo Testata:
PROTEINS-STRUCTURE FUNCTION AND GENETICS
fascicolo: 2, volume: 37, anno: 1999,
pagine: 242 - 252
SICI:
0887-3585(19991101)37:2<242:CSOTDM>2.0.ZU;2-M
Fonte:
ISI
Lingua:
ENG
Soggetto:
PURINE NUCLEOSIDE PHOSPHORYLASE; TRANSITION-STATE ANALYSIS; CELL GROWTH-FACTOR; DENSITY-FUNCTIONAL THEORY; MOLECULAR-DYNAMICS; PHOSPHOGLYCERATE KINASE; 3-DIMENSIONAL STRUCTURE; AMP NUCLEOSIDASE; ESCHERICHIA-COLI; SIMULATIONS;
Keywords:
catalytic mechanism; conformational change; domain movement; molecular dynamics; thymidine phosphorylase;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
50
Recensione:
Indirizzi per estratti:
Indirizzo: Rick, SW NCI, Adv Biomed Comp Ctr, Frederick Canc Res & Dev Ctr, SAIC Frederick, Frederick, MD 21702 USA NCI Frederick MD USA 21702 IC Frederick, Frederick, MD 21702 USA
Citazione:
S.W. Rick et al., "Computational studies of the domain movement and the catalytic mechanism of thymidine phosphorylase", PROTEINS, 37(2), 1999, pp. 242-252

Abstract

Thymidine phosphorylase (TP) is a dual substrate enzyme with two domains. Each domain binds a substrate. In the crystal structure of Escherichia coliTP, the two domains are arranged so that the two substrate binding sites are too far away for the two substrates to directly react. Molecular dynamics simulations reveal a different structure of the enzyme in which the two domains have moved to place the two substrates in close contact. This structure has a root-mean-square deviation from the crystal structure of 4.1 Angstrom. Quantum mechanical calculations-using this structure find that the reaction can proceed by a direct nucleophilic attack with a low barrier. Thismechanism is not feasible in the crystal structure environment and is consistent with the mechanism observed for other N-glycosidic enzymes, Important catalytic roles are found for the three highly conserved residues His 85,Arg 171, and Lys 190. Proteins 1999;37:242-252. (C) 1999 Wiley-Liss, Inc.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 18/09/20 alle ore 10:38:37