User:Rick H. Cote

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  • Professor of Biochemistry (Ph.D. in Molecular Biology, Univ. Wisconsin-Madison)
  • Chair, Department of Molecular, Cellular and Biomedical Sciences
  • 306 Rudman Hall
  • University of New Hampshire
  • Durham NH 03824
  • lab group web site:

Structural approaches to understanding the visual signaling pathway

Light stimulation causes the activation of the cGMP phosphodiesterase (PDE6), the central effector of the visual transduction pathway. Precise regulation of the lifetime of PDE6 activation is required to control the sensitivity, amplitude and kinetics of the light response. Our lab focuses on understanding the sequence of steps by which transducin relieves the inhibited state of the PDE6 holoenzyme, as well as identifying other proteins which may form a multi-protein complex with PDE6 to further regulate its hydrolytic activity.

Several putative PDE6 binding partners have been reported, but the significance of most of these interactions for the phototransduction mechanism is not known. In collaboration with the Chu lab (UNH), we are using protemic tools to study the ‘interactome’ of PDE6 and to characterize the PDE6 signaling complex in its dark-adapted, transiently activated, and persistently activated states.

Another active area of investigation relates to the structural and functional relatedness of the photoreceptor PDE6 enzyme family with PDE5, prevalent in vascular smooth muscle and a therapeutic target of drugs increasingly used for treatments of the cardiovascular and urogenital systems. Adverse visual effects can accompany administration of PDE5 inhibitors due to the lack of selectivity of most drugs for PDE6. Whereas PDE5 is readily expressed as a recombinant protein, efforts to express the structurally and functionally related PDE6 have met with failure. Using replacement of evolutionarily conserved amino acids that differ between the PDE5 and PDE6 families, we are identifying the amino acids that confer drug specificity and catalytic efficiency of PDE6.

Proteopedia Page Contributors and Editors (what is this?)

Rick H. Cote, Eran Hodis

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