Novel cyanide inhibition at cytochrome c1 of Rhodobacter capsulatus cytochrome bc1.

Oxidized cytochrome c(1) in photosynthetic bacterium Rhodobacter capsulatus cytochrome bc(1) reversibly binds cyanide with surprisingly high, micromolar affinity. The binding dramatically lowers the redox midpoint potential of heme c(1) and inhibits steady-state turnover activity of the enzyme. As cytochrome c(1), an auxiliary redox center of the high-potential chain of cytochrome bc(1), does not interact directly with the catalytic quinone/quinol binding sites Q(o) and Q(i), cyanide introduces a novel, Q-site independent locus of inhibition. This is the first report of a reversible inhibitor that manipulates the energetics and electron transfers of the high-potential redox chain of cytochrome bc(1), while maintaining quinone substrate catalytic sites in an intact form.

[1]  C. Slaughter,et al.  Hydroubiquinone-cytochrome c2 oxidoreductase from Rhodobacter capsulatus: definition of a minimal, functional isolated preparation. , 1993, Biochemistry.

[2]  A. Schejter,et al.  The reaction of cytochrome c with imidazole. , 1969, Biochemistry.

[3]  G. Babcock,et al.  Dioxygen activation and bond cleavage by mixed-valence cytochrome c oxidase. , 1998, Proceedings of the National Academy of Sciences of the United States of America.

[4]  J Koepke,et al.  Structure at 2.3 A resolution of the cytochrome bc(1) complex from the yeast Saccharomyces cerevisiae co-crystallized with an antibody Fv fragment. , 2000, Structure.

[5]  G. Feher,et al.  Crystallization and X-ray structure determination of cytochrome c2 from Rhodobacter sphaeroides in three crystal forms. , 1995, Acta crystallographica. Section D, Biological crystallography.

[6]  N. Sutin,et al.  Mechanisms of the reactions of cytochrome c. Rate and equilibrium constants for ligand binding to horse heart ferricytochrome c. , 1972, The Journal of biological chemistry.

[7]  J. Deisenhofer,et al.  Inhibitor binding changes domain mobility in the iron-sulfur protein of the mitochondrial bc1 complex from bovine heart. , 1998, Proceedings of the National Academy of Sciences of the United States of America.

[8]  James Barber,et al.  Length, time, and energy scales of photosystems. , 2003, Advances in protein chemistry.

[9]  J Deisenhofer,et al.  Crystal structure of the cytochrome bc1 complex from bovine heart mitochondria. , 1997, Science.

[10]  P. Rich,et al.  Cyanide and carbon monoxide binding to the reduced form of cytochrome bo from Escherichia coli. , 1995, Biochemistry.

[11]  T. A. Link,et al.  Use of specific inhibitors on the mitochondrial bc1 complex. , 1986, Methods in enzymology.

[12]  F. Daldal,et al.  Size of the amino acid side chain at position 158 of cytochrome b is critical for an active cytochrome bc1 complex and for photosynthetic growth of Rhodobacter capsulatus. , 1991, Proceedings of the National Academy of Sciences of the United States of America.

[13]  P. Rich,et al.  Photolysis of the cyanide adduct of ferrous horseradish peroxidase , 1997 .

[14]  P. Dutton,et al.  Controlling the functionality of cytochrome c(1) redox potentials in the Rhodobacter capsulatus bc(1) complex through disulfide anchoring of a loop and a beta-branched amino acid near the heme-ligating methionine. , 2001, Biochemistry.

[15]  D. J. Cohen,et al.  Spectroelectrochemical and electrochemical determination of ligand binding and electron transfer properties of myoglobin, cyanomyoglobin, and imidazolemyoglobin , 1998 .

[16]  T. A. Link,et al.  Complete structure of the 11-subunit bovine mitochondrial cytochrome bc1 complex. , 1998, Science.

[17]  A. Desideri,et al.  Azide, cyanide, fluoride, imidazole and pyridine binding to ferric and ferrous native horse heart cytochrome c and to its carboxymethylated derivative: a comparative study. , 1996, Journal of inorganic biochemistry.

[18]  L. Yu,et al.  Use of a photoactivated ruthenium dimer complex to measure electron transfer between the Rieske iron-sulfur protein and cytochrome c(1) in the cytochrome bc(1) complex. , 2000, Biochemistry.

[19]  T. Meyer,et al.  Imidazole binding to Rhodobacter capsulatus cytochrome c2. Effect of site-directed mutants on ligand binding. , 1998, The Journal of biological chemistry.

[20]  Sung-Hou Kim,et al.  Electron transfer by domain movement in cytochrome bc1 , 1998, Nature.

[21]  P. Dutton,et al.  Isolation and characterization of a two-subunit cytochrome b-c1 subcomplex from Rhodobacter capsulatus and reconstitution of its ubihydroquinone oxidation (Qo) site with purified Fe-S protein subunit. , 1998, Biochemistry.

[22]  T. Meyer,et al.  Protein dynamics: imidazole binding to class I C-type cytochromes. , 1999, Archives of biochemistry and biophysics.

[23]  U. Brandt,et al.  What information do inhibitors provide about the structure of the hydroquinone oxidation site of ubihydroquinone: Cytochromec oxidoreductase? , 1993, Journal of bioenergetics and biomembranes.

[24]  L. Esser,et al.  The crystal structure of mitochondrial cytochrome bc1 in complex with famoxadone: the role of aromatic-aromatic interaction in inhibition. , 2002, Biochemistry.