Hemopexin crystal structure

Fig. 6. Deconvolved amide F region FTIR spectra of apo- and heme-hemopexin. The amide F FTIR spectra of apo- and heme-hemopexin in D2 O were recorded and curve-fitted to resolve the individual bands. The differences between the original and fitted curves are shown in the upper traces in the panels. The estimated helix (15%), beta (54%), turn (19%), and coil (12%) content of the apo-protein are not significantly changed upon heme binding 104). This analysis was required because of the positive 231-nm elhpticity band in hemopexin and is consistent with the derived crystal structure results.

Fig. 7. The crystal structure of the C-domain of hemopexin (PDB accession number IHXN) 128) showed a four-bladed p-propeller structure, which because of sequence similarity was also expected in the N-domain. The high degree of beta structure and limited a-helix content agrees with the earlier FTIR analysis.

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.

To date, the crystal structures of 12 different MMPs have been solved. Full structures were obtained for MMP-1 (2CLT), MMP-2 (1CK7), and MMP-7 (IMMP). As for the rest, only the catalytic domains in the presence of different inhibitors were determined. The hemopexin-like domains of MMP-2 (IRTG), MMP-9 (IITV), and MMP-13 (IPEX) were crystallized, and structures were determined separately. Nuclear magnetic resonance (NMR) structures of the catalytic domains of MMP-1 (1AYK), MMP-2 (IHOV), MMP-3 (lUMS), MMP-12 (1YCM), and MMP-13 (lEUB) have also become available. 

The chemistry and biochemistry of Hpx has been reviewed and a crystal structure is available. Hemopexin is present in serum at about 10 pM and its primary function is to transport released heme to its degradation site in the parenchymal cells of the liver via receptor-mediated endocytosis. Encapsulation of a single heme by Hpx occurs via bis-histidyl protein side-chain coordination of the Fe. Spectroelectrochemical investigation of the heme-Hpx assembly gives insight into the role of Hpx in controlling the reduction potential of the heme Fe, the efficiency of electron transfer at the metal centre, the influence of bis-histidyl coordination at the Fe centre, and the possible role of Fe redox in the Hpx-mediated transport and recycling of heme. 

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