Heme-binding

A protein, designated cyctochrome c", isolated from the methylotrophic bacterium Methylophilus methylotrophus, has been studied extensively because of its unusual properties and was found to have an average molecular mass of 14293.0 Da and to contain 124 amino acid residues. The A-terminal sequence to residue 62 had been determined and the heme binding site had been located at Cys-49 and Cys-52 [12]. Further studies were concerned with determining the remainder of the sequence. 

Inhibits all forms of P450 Competes with oxygen for heme-binding site Carbene forms generated, and these bind to heme Selective inhibitors... 

Burch, M.K. and Morgan, W.T. (1985) Preferred heme binding sites of histidine-rich glycoprotein. Biochemistry 24, 5919-5924. 

Figure 8.1 Schematic of a typical cytochrome P450 protein showing the approximate locations for the heme binding domain, the proline-rich region and the I helix.

Particular ability of liver P450s3A to catalyze the oxidation of N-omega-hydroxyarginine to citrulline and nitrogen oxides and occurrence in NO synthases of a sequence very similar to the heme-binding sequence in P450s, Biochem. Biophys. Res. Commun. 192 (1993), p. 53-60... 

Yet confusion exists in the literature since authors have not always made a distinction between hemoglobin- and heme-binding plasma proteins. Nyman (N6) and Aber and Rowe (Al) have stressed the difference between these proteins. A recently discovered heme-binding (5-globulin (Nl) [originally called a2-globulin (B6)] with a higher... 

Otto, B. R., Sijbrandi, R., Luirink, J., Oudega, B., Heddle, J. G., Mizutani, K., Park, S. Y., and Tame, J. R. (2005). Crystal structure of hemoglobin protease, a heme binding autotransporter protein from pathogenic Escherichia coli. f. Biol. Chem. 280, 17339-17345. 

Curve D pyranine in the heme binding site of apomyoglobin, a site containing 30 water molecules or less. 

The functionalization of folded motifs is based on an understanding of secondary and tertiary structures (Fig. 2) and must take into account the relative positions of the residues, their rotamer populations and possible interactions with residues that do not form part of the site. For example, glutamic acid in position i has a strong propensity for salt-bridge formation, and thus reduced reactivity, if there is a Lys residue available i-4 in the sequence, but the probabihty is much less if the base is i-3 [60]. Fortunately, there is a wealth of structural information on the structural properties of the common amino acids from studies of natural proteins that provides considerable support for the design of new proteins. The naturally occurring amino acids have so far been used to construct reactive sites for catalysis [11-13], metal- and heme-binding sites [14,15,19,21,22] and for the site-selective functionalization of folded proteins [24,25]. 

B. Mutagenesis of the Proximal Heme Binding Pocket Electron Transfer Reactions of Myoglobin... 

Introduction of tbiolate ligation at position 93 has also been reported (69, 70, 73). Again subtle species-specific differences in sequence on the proximal side of the heme binding pocket result in significant differences in behavior between closely related proteins. In this case, the spectroscopic properties of the human H93C variant (69, 70) were consistent with the presence of five-coordinate, cysteine-coordinated high-spin Fe(III). On the other hand, similar studies of the corresponding... 

Perhaps the most fundamental fimctional property of a heme prosthetic group at the active site of a heme protein is the relative stability of the reduced and oxidized states of the heme iron. A number of structural characteristics of the heme binding environment provided by the apo-protein have been identified as contributing to the regulation of this equilibrium and have been reviewed elsewhere 82-84). Although a comprehensive discussion of these factors is not possible in the space available here, they can be summarized briefly. The two most significant influences of the reduction potential of the heme iron appear to be the dielectric constant of the heme environment 81, 83) and the chemical... 

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