Mohammed Ibrahim - Soluble Guanylate Cyclase Is Activated Differently by Excess NO and by YC-1: Resonance Raman Spectroscopic Evidence

Document created by Mohammed Ibrahim on Aug 22, 2014
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  Publication Details (including relevant citation   information):

  Biochemistry 2010, 49,   4864-4871.

  Abstract:

  Modulation of soluble guanylate cyclase (sGC) activity by nitric   oxide (NO) involves two distinct steps. Low-level activation of   sGC is achieved by the stoichiometric binding of NO (1-NO) to the   heme cofactor, while much higher activation is achieved by the   binding of additional NO (xsNO) at a non-heme site. Addition of   the allosteric activator YC-1 to the 1-NO form leads to activity   comparable to that of the xsNO state. In this study, the   mechanisms of sGC activation were investigated using electronic   absorption and resonance Raman (RR) spectroscopic methods. RR   spectroscopy confirmed that the 1-NO form contains   five-coordinate NO-heme and showed that the addition of NO to the   1-NO form has no significant effect on the spectrum. In contrast,   addition of YC-1 to either the 1-NO or xsNO forms alters the RR   spectrum significantly, indicating a protein-induced change in   the heme geometry. This change in the heme geometry was also   observed when BAY 41-2272 was added to the xsNO form. Bands   assigned to bending and stretching motions of the vinyl and   propionate substituents undergo changes in intensity in a pattern   suggesting altered tilting of the pyrrole rings to which they are   attached. In addition, the N−O stretching frequency increases,   with no change in the Fe−NO stretching frequency, an effect   modeled via DFT calculations as resulting from a small opening of   the Fe−N−O angle. These spectral differences demonstrate   different mechanisms of activation by synthetic activators, such   as YC-1 and BAY 41-2272, and excess NO.

  Address (URL): http://pubs.acs.org/doi/abs/10.1021/bi100506j

 

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