3LFV

crystal structure of unliganded PDE5A GAF domain

Summary for 3LFV

• Entry DOI: 10.2210/pdb3lfv/pdb
• Related: 3MF0
• Descriptor: cGMP-specific 3',5'-cyclic phosphodiesterase (1 entity in total)
• Functional Keywords: gaf, cgmp signaling, hydrolase
• Biological source: Homo sapiens (human)
• Total number of polymer chains: 2
• Total formula weight: 97724.94

Authors

Wang, H.,Robinson, H.,Ke, H. (deposition date: 2010-01-18, release date: 2010-09-22, Last modification date: 2024-02-21)

Primary citation

Wang, H.,Robinson, H.,Ke, H.
Conformation changes, N-terminal involvement, and cGMP signal relay in the phosphodiesterase-5 GAF domain.
J.Biol.Chem., 285:38149-38156, 2010

PubMed Abstract: The activity of phosphodiesterase-5 (PDE5) is specific for cGMP and is regulated by cGMP binding to GAF-A in its regulatory domain. To better understand the regulatory mechanism, x-ray crystallographic and biochemical studies were performed on constructs of human PDE5A1 containing the N-terminal phosphorylation segment, GAF-A, and GAF-B. Superposition of this unliganded GAF-A with the previously reported NMR structure of cGMP-bound PDE5 revealed dramatic conformational differences and suggested that helix H4 and strand B3 probably serve as two lids to gate the cGMP-binding pocket in GAF-A. The structure also identified an interfacial region among GAF-A, GAF-B, and the N-terminal loop, which may serve as a relay of the cGMP signal from GAF-A to GAF-B. N-terminal loop 98-147 was physically associated with GAF-B domains of the dimer. Biochemical analyses showed an inhibitory effect of this loop on cGMP binding and its involvement in the cGMP-induced conformation changes.

PubMed: 20861010
DOI: 10.1074/jbc.M110.141614

Experimental method

X-RAY DIFFRACTION (2.8 Å)