Crystal structures, of heme

Fig. 8. Crystal structure of heme-hemopexin. The crystal structure of the rabbit mesoheme-hemopexin complex (PDB accession number IQHU) (11) showed heme to be bound in a relatively exposed site between the N- and C-domains with one axial His ligand being contributed by the hinge or linking region between the domains and the other by the C-domain. Also noteworthy is the disposition of the heme with its propionate residues pointing inward and neutralized by positive charges in the binding site.

Figure 18.4 Structures of heme/Cu oxidases at different levels of detail, (a) Position of the redox-active cofactors relative to the membrane of CcO (left, only two obligatory subunits are shown) and quinol oxidase (right), (b) Electron transfer paths in mammalian CcO. Note that the imidazoles that ligate six-coordinate heme a and the five-coordinate heme are linked by a single amino acid, which can serve as a wire for electron transfer from ferroheme a to ferriheme as. (c) The O2 reduction site of mammalian CcO the numbering of the residues corresponds to that in the crystal structure of bovine heart CcO. The subscript 3 in heme as and heme 03 signifies the heme that binds O2. The structures were generated using coordinates deposited in the Protein Data Bank, lari [Ostermeier et al., 1997] Ifft [Abramson et al., 2000] (a) and locc [Tsukihara et al., 1996] (b, c).

The specific solvation of NO coordinated to Fe(III) and the resulting solvent reorganization upon NO dissociation (Fig. 3) finds some analogy with the nitrophorins, which are heme protein systems for NO transfer found in certain blood sucking insects. The crystal structure of one nitro-phorin, NP4, shows that binding of NO to the Fe(III) center leads to a collapse of the protein around the coordinated NO. The distal hemebinding pocket in nitrophorin NP4 is quite open to solvent in the absence of NO. It was postulated that collapse of the protein around the heme nitrosyl led to increased retention of bound NO at low pH (25). 

Li, H., Raman, C. S., Glaser, C. B., Blasko, E., Young,T. A., Parkinson, J. F., Whitlow, M., Poulos. T. L., Crystal structures of zinc-free and -bound heme domain of human inducible nitric-oxide synthase. Implications for dimer stability and comparison with endothelial nitric-oxide synthase, ]. Biol.Chem. 

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. 

The X-ray crystal structure of the benzhydroxamic acid complex of resting state HRP C has been solved to 2.0 A resolution 196). Important structural elements of the binding site are illustrated in Fig. 9 (see color insert). The donor molecule is located on the distal side of the heme plane and makes both hydrogen-bonded and hydrophobic interactions with the enzyme. Arg38, His42, Pro 139, and a distal water molecule located 2.6 A above heme iron contribute to an extensive hydrogen bond... 

The crystal structure of the eNOS—SEITU complex is shown in Fig. 11. As expected, the ureido group H-bonds with Glu363 similar to the way L-Arg interacts with Glu363. Two water molecules form H-bonding bridges between the inhibitor and heme propionates. The inhibitor sulfur is A from the heme iron but appears not to coordinate with iron,... 

Fig. 12. Crystal structure of the complex formed between the heme and FMN domains of cytochrome P450BM-3 133). The FMN domain docks on the proximal surface of the heme domain. The thicker trace in the heme domain highlights residues 387 to the heme ligand, Cys400. This section of polypeptide contacts the FMN and might provide an electron transfer conduit to the heme ligand. The two interacting surfaces are electrostatically complementary, with similar complementarity expected for HO and NOS.

The crystal structure of human HO-1 complexed with heme has been determined to 2.07 A (163). In order to obtain crystals for high-resolution studies 164), it was necessary to use an E. coli expressed version of HO-1 consisting of residues 1-233 (missing residues 234-288, which includes the C-terminal membrane anchor). This shorter version of HO-1 is soluble and retains about 50% wild-type activity (165). As shown in Fig. 16, HO-1 is formed exclusively by helices and connecting segments of random coil. Although the rich helical content is similar to that of... 

In the HO-1 crystal structure, the heme is hexacoordinate with a water molecule/hydroxide ion 2.0 A from the iron. This is consistent with spectral studies showing that the HO-1 heme converts from high to low spin with a pKs, 7.6-8.0 (169, 177), presumably due to titration of a water molecule resulting in hydroxide binding to heme iron. The... 

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