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- Title
Modeling and mutational analysis of the GAF domain of the cGMP-binding, cGMP-specific phosphodiesterase, PDE5
- Authors
Sopory, Shailaja; Balaji, S.; Srinivasan, N.; Visweswariah, Sandhya S.
- Abstract
The GAFa domain of the cGMP-binding, cGMP-specific phosphodiesterase (PDE5A) was modeled on the crystal structure of PDE2A GAF domain and residues involved in cGMP binding identified. Tandem GAFa and GAFb domains of PDE5A, expressed in Escherichia coli, bound cGMP (Kd 27 nM). Mutation of aspartate-299 in GAFa, suggested earlier to be critical for cGMP binding, did not abrogate cGMP binding, but mutation of F205, which formed a stacking interaction with the guanine ring of cGMP, led to complete loss of cGMP binding. Therefore, the GAFa domain of PDE5A adopts a structure similar to the GAFb domain of PDE2A, and provides the sole site for cGMP binding in PDE5A.
- Subjects
ESCHERICHIA coli; PHOSPHODIESTERASES
- Publication
FEBS Letters, 2003, Vol 539, Issue 1-3, p161
- ISSN
0014-5793
- Publication type
Article
- DOI
10.1016/S0014-5793(03)00219-9