NDLI: Identification of the γ Subunit-interacting Residues on Photoreceptor cGMP Phosphodiesterase, PDE6α′

Content Provider	Journal of Biological Chemistry (JBC)
Author	Granovsky, Alexey E. Artemyev, Nikolai O.
Abstract	Photoreceptor cGMP phosphodiesterase (PDE6) is the effector enzyme in the G protein-mediated visual transduction cascade. In the dark, the activity of PDE6 is shut off by the inhibitory γ subunit (Pγ). Chimeric proteins between cone PDE6α′ and cGMP-binding and cGMP-specific PDE (PDE5) have been constructed and expressed in Sf9 cells to study the mechanism of inhibition of PDE6 catalytic activity by Pγ. Substitution of the segment PDE5-(773–820) by the corresponding PDE6α′-(737–784) sequence in the wild-type PDE5 or in a PDE5/PDE6α′ chimera containing the catalytic domain of PDE5 results in chimeric enzymes capable of inhibitory interaction with Pγ. The catalytic properties of the chimeric PDEs remained similar to those of PDE5. Ala-scanning mutational analysis of the Pγ-binding region, PDE6α′-(750–760), revealed PDE6α′ residues essential for the interaction. The M758A mutation markedly impaired and the Q752A mutation moderately impaired the inhibition of chimeric PDE by Pγ. The analysis of the catalytic properties of mutant PDEs and a model of the PDE6 catalytic domain suggest that residues Met758 and Gln752directly bind Pγ. A model of the PDE6 catalytic site shows that PDE6α′-(750–760) forms a loop at the entrance to the cGMP-binding pocket. Binding of Pγ to Met758 would effectively block access of cGMP to the catalytic cavity, providing a structural basis for the mechanism of PDE6 inhibition.
Related Links	http://www.jbc.org/content/275/52/41258.abstract
Ending Page	41262
Starting Page	41258
Page Count	5
File Format	HTM / HTML PDF
ISSN	00219258
Journal	Journal of Biological Chemistry (JBC)
Issue Number	52
Volume Number	275
DOI	10.1074/jbc.M008094200
e-ISSN	1083351X
Language	English
Publisher	American Society for Biochemistry and Molecular Biology
Publisher Date	2000-12-29
Access Restriction	Open
Subject Keyword	CGMP phosphodiesterase (PDE) Α, β, and γ subunits of rod PDE (PDE6αβ and Pγ) Α′ subunit of cone PDE (PDE6α′) CGMP-binding, cGMP-specific PDE (PDE5 family) (PDE5) Polymerase chain reaction (PCR) MECHANISMS OF SIGNAL TRANSDUCTION
Content Type	Text
Resource Type	Article
Subject	Cell Biology Biochemistry Molecular Biology

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