Catalogo Articoli (Spogli Riviste)

OPAC HELP

Titolo:
A MUTATION IN THE HUMAN CYCLIN-DEPENDENT KINASE INTERACTING PROTEIN, CKSHS2, INTERFERES WITH CYCLIN-DEPENDENT KINASE BINDING AND BIOLOGICALFUNCTION, BUT PRESERVES PROTEIN-STRUCTURE AND ASSEMBLY
Autore:
WATSON MH; BOURNE Y; ARVAI AS; HICKEY MJ; SANTIAGO A; BERNSTEIN SL; TAINER JA; REED SI;
Indirizzi:
SCRIPPS CLIN & RES INST,DEPT MOL BIOL,MB-7,10550 N TORREY PINES RD LAJOLLA CA 92037 SCRIPPS CLIN & RES INST,DEPT MOL BIOL LA JOLLA CA 92037 CNRS,UPR 9039 F-13402 MARSEILLE 20 FRANCE
Titolo Testata:
Journal of Molecular Biology
fascicolo: 5, volume: 261, anno: 1996,
pagine: 646 - 657
SICI:
0022-2836(1996)261:5<646:AMITHC>2.0.ZU;2-G
Fonte:
ISI
Lingua:
ENG
Soggetto:
CELL-CYCLE; SCHIZOSACCHAROMYCES-POMBE; SACCHAROMYCES-CEREVISIAE; FISSION YEAST; CRYSTAL-STRUCTURE; DIVISION CYCLE; TRANSITION; MITOSIS; G1; SUBUNIT;
Keywords:
CELL CYCLE; CKSHS2; CYCLIN-DEPENDENT KINASE; SITE-DIRECTED MUTAGENESIS; CRYSTAL STRUCTURE;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Science Citation Index Expanded
Citazioni:
35
Recensione:
Indirizzi per estratti:
Citazione:
M.H. Watson et al., "A MUTATION IN THE HUMAN CYCLIN-DEPENDENT KINASE INTERACTING PROTEIN, CKSHS2, INTERFERES WITH CYCLIN-DEPENDENT KINASE BINDING AND BIOLOGICALFUNCTION, BUT PRESERVES PROTEIN-STRUCTURE AND ASSEMBLY", Journal of Molecular Biology, 261(5), 1996, pp. 646-657

Abstract

A mutation directing an amino acid substitution in the conserved P-hinge region of one of the human Cks isoforms, CksHs2, was constructed by site-directed mutagenesis. Replacement of glutamine for glutamate 63(E63Q) was predicted to stabilize the beta-interchanged dimeric and hexameric assembly of CksHs2. However, such an effect was seen only at high, non-physiological pH. Three-dimensional structures of the E63Q hexameric mutant protein were determined to 2.6 Angstrom resolution in a P4(3)2(1)2 space group and 2.1 Angstrom in the C-2 space group isostructural with wild-type, and both were shown to be virtually identicalto the refined 1.7 Angstrom wild-type structure. Thus, the E63Q mutation did not alter the wild-type structure and assembly of CksHs2 but, surprisingly, disrupted the essential biological function of the protein and significantly reduced its ability to bind to cyclin-dependent kinases. The K-d Of wild-type CksHs2 for CDK2 was 5.05 x 10(-8) M, whereas the affinity of the mutant protein for CDK2 was too low to allow adetermination. These data, coupled with the observation that monomeric but not hexameric CksHs2 interacts with cyclin-dependent kinases, suggest that glutamine 63 is likely to be directly involved in cyclin-dependent kinase binding in vitro and in vivo. (C) 1996 Academic Press Limited

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 04/12/20 alle ore 21:34:36