Theoretical investigation of a proposed (HIS 175-ASP 235-TRP 191) proton transfer system in cytochrome C peroxidase
- Rockefeller Univ., New York City, NY (USA)
- Molecular Research Institute, Palo Alto, CA (USA)
In this study, we have investigated the plausibility of a key postulated transformation of the proximal imidazole ligand (His 175) to an imidazolate by proton transfer to a nearby aspartate (Asp 235) absent in Mb. The proton relay system studied included not only models for the His 175 and Asp 235 residues but also for a nearby Trp 191 residue that could also interact with Asp 235 through hydrogen bonding and polarization. Two semiempirical quantum mechanical methods, Am1 and MNDO/H, with improved capabilities of describing H-bonded systems, were used to calculate the enthalpies of the three tautomeric forms of the proton relay system corresponding to the proton on the His, Asp, and Trp, respectively. These calculations were made for several models of the effect of the iron. Relative tautomeric enthalpies were calculated both with H-atom only optimization, keeping the heavy atoms fixed in their X-ray positions, and additional optimization that allowed the model Asp residue to relax. Transition-state enthalpies for the proton transfer from His to Asp were also calculated. The results of these studies suggest that the crucial postulated proton transfer from His to Asp is energetically favored, but only in the presence of the interaction of the iron with the imidazole ligand. Another stable form of the cluster, with competing proton transfer from the Trp to the Asp, was found only when the Asp position was allowed to optimize.
- OSTI ID:
- 6368823
- Report Number(s):
- CONF-8904365--
- Journal Information:
- International Journal of Quantum Chemistry; (USA), Journal Name: International Journal of Quantum Chemistry; (USA) Vol. 16; ISSN 0020-7608; ISSN IJQCB
- Country of Publication:
- United States
- Language:
- English
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Related Subjects
59 BASIC BIOLOGICAL SCIENCES
AMINO ACIDS
ASPARTIC ACID
AZOLES
BARYONS
CARBOXYLIC ACIDS
CATALYTIC EFFECTS
CYTOCHROMES
ELEMENTARY PARTICLES
ENZYMES
FERMIONS
HADRONS
HETEROCYCLIC COMPOUNDS
IMIDAZOLES
MASS TRANSFER
NUCLEONS
ORGANIC ACIDS
ORGANIC COMPOUNDS
ORGANIC NITROGEN COMPOUNDS
OXIDOREDUCTASES
PEROXIDASES
PIGMENTS
PROTEINS
PROTONS