Solution Structure of the cGMP Binding GAF Domain from Phosphodiesterase 5: Insights into Nucleotide Specificity, Dimerization, and cGMP-Dependent Conformational Change

Journal Article · Fri Aug 15 00:00:00 EDT 2008 · Journal of Biological Chemistry, 283(33):22749-22759

DOI:https://doi.org/10.1074/jbc.M801577200· OSTI ID:937368

Heikaus, Clemens C; Stout, Joseph R; Sekharan, Monica R; Eakin, Catherine M; Rajagopal, Ponni; Brzovic, Peter S; Beavo, Joseph A; Klevit, Rachel E

Phosphodiesterase 5 (PDE5) controls intracellular levels of cGMP through its regulation of cGMP hydrolysis. Hydrolytic activity of the C-terminal catalytic domain is increased by cGMP binding to the N-terminal GAF A domain. We present the NMR solution structure of the cGMP-bound PDE5A GAF A domain. The cGMP orientation in the buried binding pocket was defined through 37 intermolecular NOEs.

• Research Organization: Pacific Northwest National Lab. (PNNL), Richland, WA (United States). Environmental Molecular Sciences Lab. (EMSL)
• Sponsoring Organization: USDOE
• DOE Contract Number: AC05-76RL01830
• OSTI ID: 937368
• Journal Information: Journal of Biological Chemistry, 283(33):22749-22759, Vol. 283, Issue 33; ISSN 0021-9258
• Country of Publication: United States
• Language: English

Related Subjects

59 BASIC BIOLOGICAL SCIENCES
CONFORMATIONAL CHANGES
DIMERIZATION
HYDROLYSIS
NUCLEOTIDES
ORIENTATION
PHOSPHODIESTERASES
REGULATIONS
SPECIFICITY
Environmental Molecular Sciences Laboratory