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. IUBMB Life, 59: 700‐708, 2007