Sopory, Shailaja and Balaji, S and Srinivasan, N and Visweswariah, Sandhya S (2003) Modeling and mutational analysis of the GAF domain of the cGMP-binding, cGMP-specific phosphodiesterase, PDE5. In: FEBS Letters, 539 (1-3). pp. 161-166.
Restricted to Registered users only
Download (328Kb) | Request a copy
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.
|Item Type:||Journal Article|
|Additional Information:||Copyright of this article belongs to Elsevier.|
|Keywords:||cGMP;GAF domain;PDE5;Homology modeling;PDE2|
|Department/Centre:||Division of Biological Sciences > Molecular Biophysics Unit
Division of Biological Sciences > Molecular Reproduction, Development & Genetics (formed by the merger of DBGL and CRBME)
|Date Deposited:||28 Sep 2007|
|Last Modified:||19 Sep 2010 04:39|
Actions (login required)