The human soluble Guanylate Cyclase (sGC) is a heterodimeric enzyme capable of converting GTP to cyclic GMP. cGMP is an important signaling molecule that activates a cascade of secondary pathways. Activation of sGC is normally initiated by NO binding to the heme of the N-terminal HNOX domain. Under oxidative stress heme loss is observed leading to loss of function and eventually proteosomal degradation of the enzyme.<br/>We will present the first structure of the human HNOX domain in a form where the heme has been substituted by the pharmacologically relevant sGC activator, cinaciguat. This NMR derived structure is complemented with relaxation measurements that probe the dynamics of the system.<br/>We will also discuss how the increased mobility of the system may be related to the mechanism of activation of sGC.

Structure and dynamics of the HNOX domain of the human soluble guanylate cyclase

251st National Meeting (2016)

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