Jonathan Winger - The crystal structure of the catalytic domain of a eukaryotic guanylate cyclase

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      Publication Details (including relevant citation   information):

      WINGER, JA; DERBYSHIRE, ER; LAMERS, MH; MARLETTA, MA; KURIYAN, J

      BMC STRUCTURAL BIOLOGY Volume: 8 Published: OCT 7 2008

      Abstract:

      Background: Soluble guanylate cyclases generate cyclic GMP when   bound to nitric oxide, thereby linking nitric oxide levels to the   control of processes such as vascular homeostasis and   neurotransmission. The guanylate cyclase catalytic module, for   which no structure has been determined at present, is a class III   nucleotide cyclase domain that is also found in mammalian   membrane-bound guanylate and adenylate cyclases.

      Results: We have determined the crystal structure of the   catalytic domain of a soluble guanylate cyclase from the green   algae Chlamydomonas reinhardtii at 2.55 angstrom resolution, and   show that it is a dimeric molecule.

      Conclusion: Comparison of the structure of the guanylate cyclase   domain with the known structures of adenylate cyclases confirms   the close similarity in architecture between these two enzymes,   as expected from their sequence similarity. The comparison also   suggests that the crystallized guanylate cyclase is in an   inactive conformation, and the structure provides indications as   to how activation might occur. We demonstrate that the two active   sites in the dimer exhibit positive cooperativity, with a Hill   coefficient of similar to 1.5. Positive cooperativity has also   been observed in the homodimeric mammalian membrane-bound   guanylate cyclases. The structure described here provides a   reliable model for functional analysis of mammalian guanylate   cyclases, which are closely related in sequence.

      Address (URL): http://www.biomedcentral.com/1472-6807/8/42