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Titolo:
ROLE OF THE PYRROLIDINE RING OF PROLINE IN DETERMINING THE SUBSTRATE-SPECIFICITY OF CDC2 KINASE OR CDK5
Autore:
ANDO S; IKUHARA T; KAMATA T; SASAKI Y; HISANAGA S; KISHIMOTO T; ITO H; INAGAKI M;
Indirizzi:
SAGA MED SCH,CHEM LAB SAGA 849 JAPAN ASAHI CHEM IND CO LTD,ANALYT RES & COMP SCI CTR FUJI SHIZUOKA 416 JAPAN TOKYO INST TECHNOL,FAC BIOSCI,LAB CELL & DEV BIOL YOKOHAMA KANAGAWA 227 JAPAN AICHI CANC CTR,RES INST,BIOCHEM LAB NAGOYA AICHI 464 JAPAN
Titolo Testata:
Journal of Biochemistry
fascicolo: 2, volume: 122, anno: 1997,
pagine: 409 - 414
SICI:
0021-924X(1997)122:2<409:ROTPRO>2.0.ZU;2-E
Fonte:
ISI
Lingua:
ENG
Soggetto:
DIRECTED PROTEIN-KINASE; INTERMEDIATE FILAMENT REORGANIZATION; NEURONAL CDC2-LIKE KINASE; CYCLIN-DEPENDENT KINASE-5; TAU-PROTEIN; TAIL DOMAIN; BETA-TURNS; VIMENTIN; SUBUNIT; BRAIN;
Keywords:
CDC2 KINASE; CDK5; MOLECULAR DYNAMICS AND MOLECULAR MECHANICS SIMULATIONS; PEPTIDE SYNTHESIS; PHOSPHORYLATION;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Science Citation Index Expanded
Citazioni:
39
Recensione:
Indirizzi per estratti:
Citazione:
S. Ando et al., "ROLE OF THE PYRROLIDINE RING OF PROLINE IN DETERMINING THE SUBSTRATE-SPECIFICITY OF CDC2 KINASE OR CDK5", Journal of Biochemistry, 122(2), 1997, pp. 409-414

Abstract

To examine structural features of proline which are essential for theproline-directed phosphorylation by cdc2 kinase or cdk5, we prepared the peptide representing the cdc2 kinase phosphorylation site at Ser-55 in vimentin -Ser-Ser-Ser(55)-Pro(56)-Gly-Gly(58)-Ala-Tyr-NH2], the peptide containing arginine in place of Gly-58, and their derivatives containing various N-methylamino acids or proline homologs in place of Pro-BE, and tested them as substrates for the kinases, While substitution of the proline by proline homologs (L-pipecolic acid or L-azetidine-2-carboxylic acid) increased the K-m value 2- to ii-fold at utmost, substitution by N-methylamino acids (sarcosine, L-N-methylalanine, L-N-methylvaline, or L-N-methylleucine) increased the K-m value 7- to 40-fold for cdc2 kinase, For cdk5, these substitutions led to parallel effects on the K-m value to those found for cdc2 kinase; cdk5 recognizedthe peptides with a proline specificity similar to that for cdc2 kinase, These results suggest that the pyrrolidine ring of proline is important for substrate recognition by cdc2 kinase or cdk5, Molecular dynamics and molecular mechanics simulations indicated that the pyrrolidine ring of proline is optimal to stabilize a beta-turn at the phosphorylation site and that the K-m values of the peptides for the enzymes might be related to the probability of the turn structure, The results obtained here also suggest that the pyrrolidine ring of proline is required to maintain a high V-max value for cdc2 kinase or especially for cdk5, These will aid in designing specific substrates or inhibitors for cdc2 kinase or cdk5.

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Documento generato il 28/03/20 alle ore 13:28:23