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Titolo:
SUBSTRATE CHANNELING AND DOMAIN - DOMAIN INTERACTIONS IN BIFUNCTIONALTHYMIDYLATE SYNTHASE - DIHYDROFOLATE-REDUCTASE
Autore:
LIANG PH; ANDERSON KS;
Indirizzi:
YALE UNIV,SCH MED,DEPT PHARMACOL,333 CEDAR ST NEW HAVEN CT 06520 YALE UNIV,SCH MED,DEPT PHARMACOL NEW HAVEN CT 06520
Titolo Testata:
Biochemistry
fascicolo: 35, volume: 37, anno: 1998,
pagine: 12195 - 12205
SICI:
0006-2960(1998)37:35<12195:SCAD-D>2.0.ZU;2-7
Fonte:
ISI
Lingua:
ENG
Soggetto:
TRYPTOPHAN SYNTHASE; ESCHERICHIA-COLI; HETEROLOGOUS EXPRESSION; LEISHMANIA-TROPICA; CRYSTAL-STRUCTURES; TERNARY COMPLEX; KINETIC SCHEME; EPSP SYNTHASE; MECHANISM; SYNTHETASE;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Science Citation Index Expanded
Citazioni:
36
Recensione:
Indirizzi per estratti:
Citazione:
P.H. Liang e K.S. Anderson, "SUBSTRATE CHANNELING AND DOMAIN - DOMAIN INTERACTIONS IN BIFUNCTIONALTHYMIDYLATE SYNTHASE - DIHYDROFOLATE-REDUCTASE", Biochemistry, 37(35), 1998, pp. 12195-12205

Abstract

The thymidylate synthase (TS) and dihydrofolate reductase (DHFR) enzymes are found on a single polypeptide chain in several species of protozoa such as the parasitic Leishmania major. Earlier studies with the bifunctional TS-DHFR enzyme from L. major have suggested that this enzyme exhibits a phenomenon known as substrate channeling [Meek, T. D., et al. (1985) Biochemistry 24, 678-686]. This is a process by which a metabolite or intermediate is directly transferred from one enzyme active site to the next without being released free into solution. The crystal structure for the bifunctional TS-DHFR enzyme from L. major was recently solved, and it was shown that the TS active site was located 40 Angstrom from the DHFR active site [Knighton, D. R., et al. (1994) Nat. Struct. Biol. 1, 186-194]. On the basis of the crystal structure,a novel mechanism has been proposed for the channeling of the intermediate, dihydrofolate, from the TS active site to the DHFR active site [Knighton, D. R., et al. (1994) Not. Struct, Biol. 1, 186-194]. They suggest that the dihydrofolate is transferred via an ''electrostatic'' channel on the protein surface which connects the two active sites. Inthis report, we describe the use of a rapid transient kinetic analysis in examining the kinetics of substrate channeling as well as domain-domain interactions in the bifunctional TS-DHFR from L. major.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 13/07/20 alle ore 14:16:15