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Titolo:
Three-dimensional model of the cyclin-dependent kinase 1 (CDK1): Ab initioactive site parameters for molecular dynamics studies of CDKs
Autore:
Cavalli, A; Dezi, C; Folkers, G; Scapozza, L; Recanatini, M;
Indirizzi:
Univ Bologna, Dept Pharmaceut Sci, I-40126 Bologna, Italy Univ Bologna Bologna Italy I-40126 harmaceut Sci, I-40126 Bologna, Italy ETH Zurich, Inst Pharmaceut Sci, Dept Appl BioSci, Zurich, Switzerland ETHZurich Zurich Switzerland ci, Dept Appl BioSci, Zurich, Switzerland
Titolo Testata:
PROTEINS-STRUCTURE FUNCTION AND GENETICS
fascicolo: 4, volume: 45, anno: 2001,
pagine: 478 - 485
SICI:
0887-3585(200112)45:4<478:TMOTCK>2.0.ZU;2-W
Fonte:
ISI
Lingua:
ENG
Soggetto:
TYROSINE KINASE; CRYSTAL-STRUCTURE; INSULIN-RECEPTOR; INHIBITORS; PROTEIN; ATP; SUBSTRATE; MECHANISM; P13(SUC1); COMPLEX;
Keywords:
anticancer drugs; homology modeling; metallo-protein; kinase activation; selectivity and flexibility;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
38
Recensione:
Indirizzi per estratti:
Indirizzo: Recanatini, M Univ Bologna, Dept Pharmaceut Sci, Via Belmeloro 6, I-40126 Bologna, Italy Univ Bologna Via Belmeloro 6 Bologna Italy I-40126 a, Italy
Citazione:
A. Cavalli et al., "Three-dimensional model of the cyclin-dependent kinase 1 (CDK1): Ab initioactive site parameters for molecular dynamics studies of CDKs", PROTEINS, 45(4), 2001, pp. 478-485

Abstract

Cyclin-dependent kinase 1 (CDK1) is an interesting target for potential anticancer drugs, and its three-dimensional (3D) structure is presently unknown. The purpose of this work was to build a 3D model of CDK1, which could be used in drug design studies. The protein 3D structure was homology modeled, based on the known crystal structure of CDK2, and new nonbonded parameters for the Mg2+ coordination complex were developed by means of ab initio quantum chemical calculations. These parameters were both obtained and validated using the CDK2 structure as reference, and then they were used for therefinement of the CDK1 model. The resulting CDK1 structure was satisfactory and stable at room temperature, as shown by the molecular dynamics simulations carried out over a I-ns time interval on the entire protein. A numberof representative kinases in the active and inactive form, including the inactive CDK1 modeled in this work, were compared. The results illustrate the conformational variability of the activation loop of the inactive form ofthe kinases and suggest a way for selectively targeting the single CDKs. (C) 2001 Wiley-Liss, Inc.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 06/07/20 alle ore 05:02:37