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Title: Structural basis of cyclic nucleotide selectivity in cGMP dependent protein kinase II

Journal Article · · BMC Pharmacology & Toxicology
 [1];  [2];  [3];  [4];  [3];  [5];  [6];  [7];  [5];  [8];  [9]
  1. Baylor Univ., Waco, TX (United States). College of Medicine. Structural and computational Biology and Molecular Biophysics Program
  2. Rice Univ., Houston, TX (United States). Dept. of Biochemistry & Cell Biology
  3. Baylor Univ., Waco, TX (United States). College of Medicine. Dept. of Pharmacology
  4. Baylor Univ., Waco, TX (United States). College of Medicine. Verna and Marrs McLean Dept. of Biochemistry and Molecular Biology
  5. Univ. of Tokushima Graduate School (Japan). Dept. of Biological Science and Technology
  6. Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States). Berkeley Center for Structural Biology
  7. Univ. of Texas, Houston, TX (United States). MD Anderson Cancer Center. Dept. of Biochemistry and Molecular Biology
  8. Baylor Univ., Waco, TX (United States). College of Medicine. Structural and computational Biology and Molecular Biophysics Program; Univ. of Texas, Houston, TX (United States). MD Anderson Cancer Center. Dept. of Biochemistry and Molecular Biology
  9. Baylor Univ., Waco, TX (United States). College of Medicine. Structural and computational Biology and Molecular Biophysics Program; Baylor Univ., Waco, TX (United States). College of Medicine. Dept. of Pharmacology; Baylor Univ., Waco, TX (United States). College of Medicine. Verna and Marrs McLean Dept. of Biochemistry and Molecular Biology
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As a central mediator of the natriuretic peptide-cGMP signalling cascade, membrane bound type II cGMP dependent protein kinase (PKG II) is a key regulator of bone growth, renin secretion, and memory formation. It represents an important drug target for treating osteoporosis, cystic fibrosis, and memory loss [1-5]. In spite of its crucial physiological roles and its importance as a therapeutic target, little is known about its mechanisms of cyclic nucleotide selectivity and activation due to a lack of structural information. PKG II contains an Nterminal regulatory (R)-domain that binds a C-terminal catalytic (C)-domain in the absence of cGMP. Binding of cGMP to the cyclic nucleotide binding domains (CNB-A and B) within the R-domain releases the C-domain, leading to activation. We sought to understand the cyclic nucleotide selectivity and activation mechanisms of PKG II by studying each CNB domain.

Research Organization:
Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States)
Sponsoring Organization:
USDOE Office of Science (SC)
Grant/Contract Number:
AC02-05CH11231
OSTI ID:
1629590
Journal Information:
BMC Pharmacology & Toxicology, Vol. 16, Issue S1; ISSN 2050-6511
Publisher:
BioMed CentralCopyright Statement
Country of Publication:
United States
Language:
English

References (10)

Sildenafil Acts as Potentiator and Corrector of CFTR but Might be not Suitable for the Treatment of CF Lung Disease journal January 2012
Intestinal Secretory Defects and Dwarfism in Mice Lacking cGMP-Dependent Protein Kinase II journal December 1996
Type II cGMP-dependent Protein Kinase Mediates Osteoblast Mechanotransduction journal March 2009
Molecular properties and biological functions of cGMP-dependent protein kinase II journal January 2005
Membrane targeting of cGMP-dependent protein kinase is required for cystic fibrosis transmembrane conductance regulator Cl- channel activation journal February 1998
Structural Basis for Cyclic-Nucleotide Selectivity and cGMP-Selective Activation of PKG I journal January 2014
Feedback Control Through cGMP-Dependent Protein Kinase Contributes to Differential Regulation and Compartmentation of cGMP in Rat Cardiac Myocytes journal November 2010
Cyclic AMP compartments and signaling specificity: Role of cyclic nucleotide phosphodiesterases journal December 2013
Cell Shape and Negative Links in Regulatory Motifs Together Control Spatial Information Flow in Signaling Networks journal May 2008
Compartmentation and compartment-specific regulation of PDE5 by protein kinase G allows selective cGMP-mediated regulation of platelet functions journal August 2008

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