Molecular model of the cyclic GMP-binding domain of the cyclic GMP-gated ion channel.
The structure of the cyclic GMP-binding domain of the cyclic GMP-gated ion channel from bovine retinal rod photoreceptors has been modeled by analogy to the crystal structure of the homologous cyclic AMP-binding domain of catabolite gene activator protein (CAP). The modeled cyclic GMP-binding domain has a three-residue deletion and a five-residue insertion between beta strands compared to CAP. The major interactions of the ion channel with cyclic GMP are similar to those observed for cyclic AMP bound to CAP and predicted for cGMP bound to the cGMP-dependent protein kinase: Gly 543 and Glu 544 make hydrogen-bond interactions with the ribose 2'-OH, Arg 559 forms an ion pair with the charged phosphate oxygen, and Thr 560 forms hydrogen-bond interactions with an exocyclic phosphate oxygen and with the 2-amino group of cGMP. Three additional potential interactions were predicted from the model structure. Ile 545 O and Ser 546 OH form hydrogen-bond interactions with an exocyclic phosphate oxygen, and Phe 533 may interact with the aromatic ring of cGMP. This model is in agreement with both the analogue binding experiments and the mutational analysis of Thr 560.
Kumar
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Department of Pharmacology, Jefferson Cancer Institute, Philadelphia, Pennsylvania 19107.
Weber
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D000595:Amino Acid Sequence; D000818:Animals; D002352:Carrier Proteins / Q000737:chemistry*; D002417:Cattle; D002373:Cyclic AMP Receptor Protein / Q000737:chemistry*; D006152:Cyclic GMP / Q000737:chemistry*; D047908:Intracellular Signaling Peptides and Proteins; D015640:Ion Channel Gating; D008958:Models, Molecular; D008969:Molecular Sequence Data; D011487:Protein Conformation; D011956:Receptors, Cell Surface / Q000737:chemistry; D016415:Sequence Alignment; D013329:Structure-Activity Relationship
D002352:Carrier Proteins; D002373:Cyclic AMP Receptor Protein; D047908:Intracellular Signaling Peptides and Proteins; D011956:Receptors, Cell Surface; C022994:cyclic GMP-binding protein; D006152:Cyclic GMP