title: Bis-histidine-coordinated hemes in four-helix bundles: how the geometry of the bundle controls the axial imidazole plane orientations in transmembrane cytochromes of mitochondrial complexes II and III and related proteins.
abstract: Early investigation of the electron paramagnetic resonance spectra of bis-histidine-coordinated membrane-bound ferriheme proteins led to the description of a spectral signal that had only one resolved feature. These became known as "highly anisotropic low-spin" or "large g(max)" ferriheme centers. Extensive work with small-molecule model heme complexes showed that this spectroscopic signature occurs in bis-imidazole ferrihemes in which the planes of the imidazole ligands are nearly perpendicular, deltaphi = 57-90 degrees. In the last decade protein crystallographic studies have revealed the atomic structures of a number of examples of bis-histidine heme proteins. A frequent characteristic of these large g(max) ferrihemes in membrane-bound proteins is the occurrence of the heme within a four-helix bundle with a left-handed twist. The histidine ligands occur at the same level on two diametrically opposed helices of the bundle. These ligands have the same side-chain conformation and ligate heme iron on the bundle axis, resulting in a quasi-twofold symmetric structure. The two non-ligand-bearing helices also obey this symmetry, and have a conserved small residue, usually glycine, where the edge of the heme ring makes contact with the helix backbones. In many cases this small residue is preceded by a threonine or serine residue whose side-chain hydroxyl oxygen acts as a hydrogen-bond acceptor from the N(delta1) atom of the heme-ligating histidine. The deltaphi angle is thus determined by the common histidine side-chain conformation and the crossing angle of the ligand-bearing helices, in some cases constrained by hydrogen bonds to the serine/threonine residues on the non-ligand-bearing helices.
authors.affiliation: Department of Biochemistry and Molecular Biology, SUNY Upstate Medical University, 750 East Adams Street, Syracuse, NY 13210, USA.
authors.forename: Edward A
authors.initials: EA
authors.lastname: Berry
authors.forename: F Ann
authors.initials: FA
authors.lastname: Walker
mesh_terms: D002462:Cell Membrane / Q000737:chemistry / Q000201:enzymology*; D003580:Cytochromes / Q000737:chemistry* / Q000378:metabolism*; D006418:Heme / Q000737:chemistry* / Q000378:metabolism*; D006639:Histidine / Q000737:chemistry / Q000378:metabolism; D007093:Imidazoles / Q000737:chemistry*; D008928:Mitochondria / Q000737:chemistry / Q000201:enzymology*
chemical_list: D003580:Cytochromes; D007093:Imidazoles; D006418:Heme; D006639:Histidine; C029899:imidazole