Distal histidine residue

The A0 component is observed on reducing the pH or mutating the distal histidine residue (His64) [9a, 12]. In addition, an X-ray study of MbCO at low pH [3b] has demonstrated that His64 is far from the ligand and out of the heme pocket. On this basis the A0 state is usually associated with a protein substate in which the CO is in an apolar environment. 

Classical simulations of MbCO using the CHARMM force field were performed for different tautomerization states of the distal histidine residue (His64) [33], These simulations showed that when His64 is protonated at N,5 (denoted the tautomer) it often rotates such that it exposes either the N,>—H bond or the un-protonated N atom to the CO, as depicted in Scheme 3.4. We... 

The first step of peroxidase catalysis involves binding of the peroxide, usually H2C>2, to the heme iron atom to produce a ferric hydroperoxide intermediate [Fe(IE)-OOH]. Kinetic data identify an intermediate prior to Compound I whose formation can be saturated at higher peroxide concentrations. This elusive intermediate, labeled Compound 0, was first observed by Back and Van Wart in the reaction of HRP with H2O2 [14]. They reported that it had absorption maxima at 330 and 410 nm and assigned these spectral properties to the ferric hydroperoxide species [Fe(III)-OOH]. They subsequently detected transient intermediates with similar spectra in the reactions of HRP with alkyl and acyl peroxides [15]. However, other studies questioned whether the species with a split Soret absorption detected by Back and Van Wart was actually the ferric hydroperoxide [16-18], Computational prediction of the spectrum expected for Compound 0 supported the structure proposed by Baek and Van Wart for their intermediate, whereas intermediates observed by others with a conventional, unsplit Soret band may be complexes of ferric HRP with undeprotonated H2O2, that is [Fe(III)-HOOH] [19]. Furthermore, computational analysis of the peroxidase catalytic sequence suggests that the formation of Compound 0 is preceded by formation of an intermediate in which the undeprotonated peroxide is coordinated to the heme iron [20], Indeed, formation of the [Fe(III)-HOOH] complex may be required to make the peroxide sufficiently acidic to be deprotonated by the distal histidine residue in the peroxidase active site [21],... 

A hydrogen bond (dotted green line) donated by the distal histidine residue to the bound oxygen molecule helps stabilize oxymyoglobin. 

E. coli have also been determined (3, 9, 24-26). Figure 1 depicts the polypeptide backbone of the yeast enzyme, indicating the position of the heme, and the proximal and distal histidine residues. The structure can be divided into N- and C-terminal domains, and the heme is in a cavity at the domain interface. The substrate access channel is also at the domain interface and is discussed in Section V. The secondary structure is dominated by a-helices with only a small amount of jS-sheet in the proximal domain. The refined structures of the recombinant wild-type enzymes are essentially identical to that of the yeast enzyme, but small differences are observed in the mutants around the mutated residues (3). 

Given that the distal His52 is a key residue in the rapid formation of compound I, then why does metmyoglobin, which also possesses a distal histidine residue, react with H2O2 much more slowly than CCP The rate constants for the bimolecular reaction of CCP and metmyo-... 

Belleli et al. (111) have utilized RSSF to investigate the influence of the distal histidine residue on the dissociation of cyanide from ferrous (Fe2+) myoglobin. Rapid mixing of a ferric-cyanide complex with dithionite results in the rapid formation of a spectroscopically distinguishable ferrous-cyanide complex, which slowly decomposes to yield reduced myoglobin and HCN. In this study, the RSSF spectral changes and kinetic time courses of both horse heart and sperm... 

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