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Titolo:
Cyclin H activation and drug susceptibility of the Pfmrk cyclin dependent protein kinase from Plasmodium falciparum
Autore:
Waters, NC; Woodard, CL; Prigge, ST;
Indirizzi:
Walter Reed Army Med Ctr, Walter Reed Army Inst Res, Div Expt Therapeut, Washington, DC 20307 USA Walter Reed Army Med Ctr Washington DC USA 20307 Washington, DC 20307 USA
Titolo Testata:
MOLECULAR AND BIOCHEMICAL PARASITOLOGY
fascicolo: 1, volume: 107, anno: 2000,
pagine: 45 - 55
SICI:
0166-6851(20000315)107:1<45:CHAADS>2.0.ZU;2-H
Fonte:
ISI
Lingua:
ENG
Soggetto:
TRANSCRIPTION FACTOR TFIIH; CELL-CYCLE; CDC2-RELATED KINASE; CATALYTIC SUBUNIT; PHOSPHORYLATION; GENE; CDC2; INHIBITORS; COMPLEX; LOCALIZATION;
Keywords:
Pfmrk; cyclin dependent protein kinase; cyclin H; olomoucine; Plasmodium falciparum; drug discovery; molecular model;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
43
Recensione:
Indirizzi per estratti:
Indirizzo: Waters, NC Walter Reed Army Med Ctr, Walter Reed Army Inst Res, Div Expt Therapeut, Washington, DC 20307 USA Walter Reed Army Med Ctr Washington DC USA 20307 DC 20307 USA
Citazione:
N.C. Waters et al., "Cyclin H activation and drug susceptibility of the Pfmrk cyclin dependent protein kinase from Plasmodium falciparum", MOL BIOCH P, 107(1), 2000, pp. 45-55

Abstract

The eukaryotic cell cycle is regulated by a group of highly conserved cyclin dependent protein kinases (CDKs). Several CDKs have been identified in Plasmodium falciparum, however, their regulatory mechanisms as well as theirrole in parasite growth and differentiation are not understood fully. To further our understanding of Plasmodium, CDK regulation, we have characterized Pfmrk kinase activity. Pfmrk was expressed and purified as a 6xHis tagged recombinant protein from Escherichia coli and assayed for histone H1 kinase activity. Pfmrk has significant histone H1 kinase activity and is autophosphorylated in vitro. Human cyclin H forms a stable complex with Pfmrk andstimulates kinase activity. This is the first indication that Plasmodial CDKs are partially regulated by cyclin subunits, as are human CDKs. CDKs areattractive drug targets due to their role in cellular proliferation. Specific CDK inhibitors were selected to evaluate Pfmrk as a potential drug target. Olomoucine and roscovitine failed to inhibit Pfmrk kinase activity which places Pfmrk with a class of CDKs that are insensitive to these compounds. A molecular model of Pfmrk provides a structural explanation for the failure of these compounds to inhibit Pfmrk. (C) 2000 Elsevier Science B.V. Allrights reserved.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 04/07/20 alle ore 14:00:28