Structural insights into sGC

The membrane and soluble guanylyl cyclases (sGCs) are key families of enzymes that produce the second messenger cGMP. Although both families recognize different ligands and have therefore different N-terminal input domains, they do have similar C-terminal output domains containing a coiled-coil domain and a guanylyl cyclase catalytic domain. We present here our latest structure-function studies on both the sGC and membrane guanylyl cyclases in an effort to enhance our molecular understanding of these receptors to delineate their similarities and differences. Our studies include a new 2.15 Å crystal structure of part of sGC and mutagenesis studies of these families of guanylyl cyclases thereby providing new insights into the structure, activation, and regulation of these receptors. from 4th International Conference of cGMP Generators, Effectors and Therapeutic Implications Regensburg, Germany. 19–21 June 2009