Crystal structure of nitric oxide inhibited cytochrome c peroxidase
- Univ. of California, San Diego, La Jolla (USA)
- Center for Advanced Research in Biotechnology, Rockville, MD (USA)
The authors have collected X-ray diffraction data from a crystal of cytochrome c peroxidase (CCP) complexed with the inhibitor nitric oxide to a resolution of 2.55 {angstrom}. A difference Fourier map shows density indicating the NO ligand is bound to the heme iron at the sixth coordination site in a bent configuration. Structural adjustments were determined by least-squares refinement that yielded an agreement residual of R = 0.18. The orientation of the ligand, tilting toward Arg-48, causes adjustment in the position of this nearby polar side chain. As a model for the substrate hydrogen peroxide, this geometry is consistent with the suggestion that Arg-48 serves to polarize the O-O peroxide bond to promote heterolytic cleavage of the bond. Strong difference density is also observed near residues 190-194, especially around the indole ring of Trp-191. The density indicates movement of the indole ring away from the proximal His-175 imidazole ring by about 0.25 {angstrom}, which appears to cause perturbation of the neighboring residues. The response of Trp-191 on the proximal side of the heme to binding nitric oxide on the distal side probably results from delocalization of the electron density of the ligand. Relevant to this is the recent finding that a mutant in which Trp-191 is replaced by phenylalanine has dramatically reduced activity, less than 0.05% of the parent activity. Characterization of this mutant showed in particular that electron transfer from cytochrome c was severely hindered. This mutagenesis result combined with the sensitivity of the position of Trp-191 to the electronic character of the sixth coordination site ligand leads us to speculate on the role of Trp-191 in electron transfer.
- OSTI ID:
- 7189588
- Journal Information:
- Biochemistry; (USA), Vol. 27:21; ISSN 0006-2960
- Country of Publication:
- United States
- Language:
- English
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Related Subjects
62 RADIOLOGY AND NUCLEAR MEDICINE
NITRIC OXIDE
BIOLOGICAL EFFECTS
PEROXIDASES
INHIBITION
X-RAY DIFFRACTION
ARGININE
COMPLEXES
CRYSTALLOGRAPHY
CYTOCHROMES
FOURIER ANALYSIS
GEOMETRY
HISTIDINE
MOLECULAR STRUCTURE
MUTANTS
PHENYLALANINE
TRYPTOPHAN
YEASTS
AMINO ACIDS
AROMATICS
AZAARENES
AZOLES
CARBOXYLIC ACIDS
CHALCOGENIDES
COHERENT SCATTERING
DIFFRACTION
ENZYMES
EUMYCOTA
FUNGI
HETEROCYCLIC ACIDS
HETEROCYCLIC COMPOUNDS
IMIDAZOLES
INDOLES
MATHEMATICS
MICROORGANISMS
NITROGEN COMPOUNDS
NITROGEN OXIDES
ORGANIC ACIDS
ORGANIC COMPOUNDS
ORGANIC NITROGEN COMPOUNDS
OXIDES
OXIDOREDUCTASES
OXYGEN COMPOUNDS
PIGMENTS
PLANTS
PROTEINS
PYRROLES
SCATTERING
560300* - Chemicals Metabolism & Toxicology
550602 - Medicine- External Radiation in Diagnostics- (1980-)