DFT studies of NO activation of sGC

INOR 100

Alexander Barabanschikov, a.barabanschikov@neu.edu1, J. Timothy Sage, jtsage@neu.edu1, Nathan J. Silvernail2, W. Robert Scheidt, scheidt.1@nd.edu2, Jiyong Zhao, jzhao@aps.anl.gov3, Wolfgang Sturhahn, sturhahn@aps.anl.gov3, and E. Ercan Alp, eea@aps.anl.gov3. (1) Department of Physics, Northeastern University, 110 Forsyth St., Boston, MA 02115, (2) Department of Chemistry and Biochemistry, University of Notre Dame, Notre Dame, IN 46556, (3) Advanced Photon Source, Argonne National Laboratory, 9700 S. Cass Ave., Argonne, IL 60439
Many important cardiovascular and neural system processes are triggered by activation of the enzyme soluble guanylate cyclase (sGC), a sensor of NO widely thought to be activated through binding of NO to heme. We report DFT calculations on various porphyrins and heme protein active sites to test the hypothesis that activation of sGC is associated with disruption of the Fe-histidine bond to the protein. We demonstrate that NO binding significantly weakens this bond. Also, comparing the predicted vibrational spectra of these compounds with nuclear resonance vibrational spectroscopy (NRVS) measurements identifies the Fe-histidine stretching mode, a reaction coordinate for histidine dissociation in NO-ligated heme proteins. Comparison of 5-coordinate and 6-coordinate NO and CO compounds provides additional tests of the hypothesis.
 

Inorganic Modeling of Biological Systems
1:30 PM-5:10 PM, Sunday, August 19, 2007 BCEC -- 208, Oral

Division of Inorganic Chemistry

The 234th ACS National Meeting, Boston, MA, August 19-23, 2007