Role of the pyrrolidine ring of proline in determining the substrate specificity of cdc2 kinase or cdk5.

Role of the pyrrolidine ring of proline in determining the substrate specificity of cdc2 kinase or cdk5. Research Abstract Details 

Research Abstract Table of Contents

Jump to the:

Role of the pyrrolidine ring of proline in determining the substrate specificity of cdc2 kinase or cdk5. Abstract Text:

S Ando,T Ikuhara,T Kamata,Y Sasaki,S Hisanaga,T Kishimoto,H Ito,M Inagaki,

To examine structural features of proline which are essential for the proline-directed phosphorylation by cdc2 kinase or cdk5, we prepared the peptide representing the cdc2 kinase phosphorylation site at Ser-55 in vimentin [Ser-Leu-Tyr-Ser-Ser-Ser55-Pro56-Gly-Gly58-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-56, 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 4-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 recognized the 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.

Role of the pyrrolidine ring of proline in determining the substrate specificity of cdc2 kinase or cdk5. Publishing Authors By Initials

S Ando,T Ikuhara,T Kamata,Y Sasaki,S Hisanaga,T Kishimoto,H Ito,M Inagaki,

For similar macromolecular substances: polymers: biopolymers: intermediate filament proteins: vimentin research abstracts see: macromolecular substances: polymers: biopolymers: intermediate filament proteins: vimentin research

PUBMED ID PMID:

MEDLINE DATE:

Role of the pyrrolidine ring of proline in determining the substrate specificity of cdc2 kinase or cdk5. Journal Published:

PUBLICATION TYPE: Research Support, Non-U.S. Gov

Journal: Journal of biochemistry

VOLUME: 122

Page Numbers: 409-14

Journal Abbreviation: J. Biochem.

ISSN: 0021-924X

DAY: 19

MONTH: Aug

YEAR: 1997

Role of the pyrrolidine ring of proline in determining the substrate specificity of cdc2 kinase or cdk5. Information

Number of References:

LANGUAGE: eng

NlmUniqueID: 376600

Role of the pyrrolidine ring of proline in determining the substrate specificity of cdc2 kinase or cdk5. Keywords Mesh Terms:

KEYWORDS: Vimentin

MESH TERMS: metabolism

Chemical & Substance for Abstract: Role of the pyrrolidine ring of proline in determining the substrate specificity of cdc2 kinase or cdk5. Information

Substance Name: Protein-Serine-Threonine Kinases

Registry Number: EC 2.7.11.1

Grant and Affiliation Information for Role of the pyrrolidine ring of proline in determining the substrate specificity of cdc2 kinase or cdk5.

AFFILIATION: Laboratory of Chemistry, Saga Medical School. andoh-s@smsnet.saga-med.ac.jp

Country: JAPAN

AGENCY:

GRANT:

ACRONYM:

MEDLINETA: J Biochem

REFSOURCE:

DATABASENAME:

ACCESSION NUMBER:

Number Hits: 0

Role of the pyrrolidine ring of proline in determining the substrate specificity of cdc2 kinase or cdk5 Related Publications

• A novel GIP receptor splice variant influences GIP sensitivity of pancreatic -cells in obese mice.
• An efficient method for protein phosphorylation using the artificially introduced of cognate-binding modules into kinases and substrates.
• Anti-prolactin (PRL) autoantibodies suppress PRL bioactivity in patients with macroprolactinaemia.
• Assessing the monophyly of chlorophyll-c containing plastids by multi-gene phylogenies under the unlinked model conditions.
• Complete sequence-specific 1H nuclear magnetic resonance assignments for mouse epidermal growth factor.
• Conformations of fibroblast and E. coli-derived recombinant human interferon-beta s as studied by nuclear magnetic resonance and circular dichroism.
• Crystallization and preliminary crystallographic analysis of the Tob-hCaf1 complex.
• Determination of Fluorescence-Labeled Asparaginyl-Oligosaccharide in Glycoprotein by Reversed-Phase Ultraperformance Liquid Chromatography with Electrospray Ionization Time-of-Flight Mass Spectrometry.
• Genetic inactivation of GIP signaling reverses aging-associated insulin resistance through body composition changes.
• Histopathological Variation of Primary Mucosa-associated Lymphoid Tissue Lymphoma of the Oral Cavity.
• Identification of phosphorylation sites on glial fibrillary acidic protein for cdc2 kinase and Ca(2+)-calmodulin-dependent protein kinase II.
• Ligand-binding enhances the affinity of dimerization of the extracellular domain of the epidermal growth factor receptor.
• Localization of mouse mitochondrial SIRT proteins: Shift of SIRT3 to nucleus by co-expression with SIRT5.
• MECT1-MAML2 fusion transcript defines a favorable subset of mucoepidermoid carcinoma.
• N-terminal half of a mitochondrial presequence peptide takes a helical conformation when bound to dodecylphosphocholine micelles: a proton nuclear magnetic resonance study.
• Novel oligosaccharides with the sialyl-Le(a) structure in human milk.
• Phosphorylation and reorganization of vimentin by p21-activated kinase (PAK).
• Production of a site- and phosphorylation state-specific antibody.
• Rapid projection of crystal grain orientation distribution in aluminium alloy sheets by synchrotron X-ray diffraction.
• Recombinant expression, biochemical characterization and stabilization through proteolysis of an L-glutamate oxidase from Streptomyces sp. X-119-6.
• Role of the pyrrolidine ring of proline in determining the substrate specificity of cdc2 kinase or cdk5.
• Solution structure of cysteine-rich domain of protein kinase C alpha.
• Solution structure of the SH2 domain of Grb2/Ash complexed with EGF receptor-derived phosphotyrosine-containing peptide.
• Soybean-derived phosphatidylinositol inhibits in vivo low concentrations of amyloid beta protein-induced degeneration of hippocampal neurons in V337M human tau-expressing mice.
• Strategies for regulating allergic responses.
• Structural basis for the transforming activity of human cancer-related signaling adaptor protein CRK.
• Structure and quantum chemical analysis of NAD+-dependent isocitrate dehydrogenase: hydride transfer and co-factor specificity.
• Structure of the antitumour enzyme L-methionine gamma-lyase from Pseudomonas putida at 1.8 A resolution.
• Tertiary structure of mouse epidermal growth factor determined by two-dimensional 1H NMR.
• The cooperative role of OsCnfU-1A domain I and domain II in the iron sulphur cluster transfer process as revealed by NMR.