Cytochrome c´ (cyt c´) is found in the periplasmic space of denitrifying bacteria where it is thought to mediate the transfer of NO between the nitrogen-cycle enzymes dissimilatory nitrite reductase and nitric oxide reductase. It contains a 5-coordinate (5c) His-ligated haem that shares spectroscopic and ligand-binding properties with the haem group in the sensory domain of soluble guanylate cyclase (sGC). The latter is an extremely important enzyme involved in the control of vasodilation and blood clotting. Curiously, the enzyme is activated up to 200-fold by the binding of NO to the haem, whereas the binding of CO gives rise to only a mild stimulation of activity. Through X-ray crystallography we have studied NO and CO binding to cyt c´. CO binds to the distal face to give a 6-coordinate (6c) adduct. By contrast, NO binding gives rise to a 5c adduct through the displacement of the proximal His, to give a novel and unexpected proximal binding mode for NO. These results are also supported by a range of spectroscopies. In the absence of a crystal structure for sGC we propose that cyt c´ provides a structural model for the haem domain of this enzyme and thereby helps to explain the differential effects of NO and CO on its activity.
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Conference Article|
June 01 2003
A two-faced molecule offers NO explanation: the proximal binding of nitric oxide to haem
D.M. Lawson;
D.M. Lawson
1
*Department of Biological Chemistry, John Innes Centre, Norwich NR4 7UH, U.K.
1To whom correspondence should be addressed (e-mail david.lawson@bbsrc.ac.uk).
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C.E.M. Stevenson;
C.E.M. Stevenson
*Department of Biological Chemistry, John Innes Centre, Norwich NR4 7UH, U.K.
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C.R. Andrew;
C.R. Andrew
†Department of Chemistry, Eastern Oregon University, 1 University Boulevard, La Grande, OR 97850-2899, U.S.A.
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S.J. George;
S.J. George
*Department of Biological Chemistry, John Innes Centre, Norwich NR4 7UH, U.K.
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R.R. Eady
R.R. Eady
*Department of Biological Chemistry, John Innes Centre, Norwich NR4 7UH, U.K.
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Publisher: Portland Press Ltd
Online ISSN: 1470-8752
Print ISSN: 0300-5127
© 2003 Biochemical Society
2003
Biochem Soc Trans (2003) 31 (3): 553–557.
Citation
D.M. Lawson, C.E.M. Stevenson, C.R. Andrew, S.J. George, R.R. Eady; A two-faced molecule offers NO explanation: the proximal binding of nitric oxide to haem. Biochem Soc Trans 1 June 2003; 31 (3): 553–557. doi: https://doi.org/10.1042/bst0310553
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