Heme-hemopexin: A 'chronosteric' heme-protein

Abstract

Hemopexin (HPX) serves as scavenger and transporter of toxic plasma heme to the liver. HPX is formed by two four-bladed β-propeller domains, resembling two thick disks that lock together at a 90° angle. The heme is bound between the two β-propeller domains in a pocket formed by the interdomain linker peptide. Residues His213 and His266 coordinate the heme iron atom giving a stable bis-histidyl complex. The HPX-heme geometry is reminiscent of heme-proteins endowed with ligand binding and (pseudo-)enzymatic properties. HPX-heme binds reversibly CO, •NO, and cyanide by detaching His213; however, O2 induces HPX-heme(II) oxidation. Furthermore, HPX-heme(II) facilitates •NO/O2 and •NO/peroxynitrite scavenging. Heme sequestering by HPX prevents heme-mediated activation of oxidants which induce the low-density lipoprotein oxidation. Here, ligand binding and (pseudo-)enzymatic properties of HPX-heme are reviewed. HPX, acting not only as a heme carrier but also displaying transient heme-based ligand binding and (pseudo-)enzymatic properties, could be considered a 'chronosteric' heme-protein. © 2007 IUBMB.