Document Detail

Catalytic site amino acids of PKGI-alpha influence allosteric cGMP binding .
MedLine Citation:
PMID:  23277076     Owner:  NLM     Status:  In-Data-Review    
Ser-64, an autophosphorylation site in the autoinhibitory subdomain of cGMP-dependent protein kinase type I-alpha (PKGI-alpha), lowers affinity for cGMP and suppresses catalytic activity (1). Using the structure of homologous cAMP-dependent protein kinase as a model, three conserved residues (Gln-401, His-404, Cys-518) in the PKGI-alpha catalytic site are predicted to be juxtaposed to Ser-64 (2). Individual point mutants (Q401A, H404A and C518A) and a double mutant (S64A/H404A) have been generated. cGMP or cAMP affinities (Ka) of each mutant protein for phosphotransferase activation and allosteric (3H)cGMP-binding affinity (KD) of each mutant protein are significantly improved over those of wild-type (WT) PKGI-alpha. However, affinities (Km) of the mutant PKGs for peptide substrates or ATP are unaltered. Kinase activity ratio (-GMP/+cGMP) of H404A is greater than that for WT, Q401A, or C518A, and similar to that for S64A and S64A/H404A. These results reveal a unique mechanism whereby catalytic domain residues predicted to be spatially close to Ser-64 of the regulatory domain weaken the intrinsically high affinity of PKGI-alpha for cGMP and provide for autoinhibition of catalytic activity.
Jennifer L Busch; Thomas M Bridges; Robyn Richie-Jannetta; Brian P Hollett; Sharron H Francis; Jackie D Corbin
Related Documents :
24900696 - Selective inhibitors of fibroblast activation protein (fap) with a (4-quinolinoyl)-glyc...
24682446 - A β-glucosidase from novosphingobium sp. gx9 with high catalytic efficiency toward iso...
24115166 - Therapeutic potentials of ecto-nucleoside triphosphate diphosphohydrolase, ecto-nucleot...
23458156 - Cooperative function and mutual stabilization of the half atp-binding cassette transpor...
21380806 - Identification and evaluation of neutral sphingomyelinase 2 inhibitors.
22761366 - Potential electrostatic interactions in multiple regions affect human metapneumovirus f...
Publication Detail:
Type:  Journal Article     Date:  2013-01-01
Journal Detail:
Title:  Frontiers in bioscience (Scholar edition)     Volume:  5     ISSN:  1945-0524     ISO Abbreviation:  Front Biosci (Schol Ed)     Publication Date:  2013  
Date Detail:
Created Date:  2013-01-01     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  101485241     Medline TA:  Front Biosci (Schol Ed)     Country:  United States    
Other Details:
Languages:  eng     Pagination:  650-60     Citation Subset:  IM    
Biology Department, Wheaton College, 501 College Avenue, Wheaton, IL 60187.
Export Citation:
APA/MLA Format     Download EndNote     Download BibTex
MeSH Terms

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine

Previous Document:  Urban PM2.5 activates GAPDH and induces RBC damage in COPD patients .
Next Document:  Migration of retinal pigment epithelial cells is EGFR/PI3K/AKT dependent .