Investigation of the mechanisms of regulations, activation, and deactivation of Guanylate Cyclase, the endogenous NO-receptor, and NO-sensors

Abstract : The endogenous NO receptor, soluble guanylate cyclase (sGC) is the subject of this thesis. This enzyme synthesizes cGMP after NO binding. The main tool used is time-resolved picosecond-nanosecond absorption spectroscopy. We have shown that the simultaneous binding of CO and activators (YC-1, Bay 41-2272) induce a 5c heme-CO, like NO, explaining the synergistic activation. We identified all steps of the sGC-NO interaction by measuring the dynamics from picosecond to second. This dynamics of the entire protein is compared with that of the isolated beta subunit (1-190) and bacterial NO sensors. A myoglobin mutant (H93C) was used as a model for the study of heme in the 4- and 5-coordinated states. Finally, we measured the band III absorption of Mb and Hb to measure the movement of the heme iron after NO binding. We also investigated a potential inhibitor and an endogenous ligand of sGC.
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Life Sciences [q-bio]. Ecole Polytechnique X, 2010. English
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Byung-Kuk Yoo. Investigation of the mechanisms of regulations, activation, and deactivation of Guanylate Cyclase, the endogenous NO-receptor, and NO-sensors. Life Sciences [q-bio]. Ecole Polytechnique X, 2010. English. 〈tel-00557106〉

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