title: Weak-field anions displace the histidine ligand in a synthetic heme peptide but not in N-acetylmicroperoxidase-8: possible role of heme geometry differences.
abstract: We have recently reported that aquo and thioether complexes of the ferric cytochrome c heme peptide N-acetylmicroperoxidase-8 (FeIII-1) exhibit greater low-spin character than do the corresponding complexes of a synthetic, water-soluble, monohistidine-ligated heme peptide (FeIII-2; Cowley, A. B.; Lukat-Rodgers, G. S.; Rodgers, K. R.; Benson, D. R. Biochemistry 2004, 43, 1656-1666). Herein we report results of studies showing that weak-field ligands bearing a full (fluoride, chloride, hydroxide) or partial (phenoxide, thiocyanate) negative charge on the coordinating atom trigger dissociation of the axial His ligand in FeIII-2 but not in FeIII-1. We attribute the greater sensitivity of His ligation in FeIII-1 to weak-field anionic ligands than to weak-field neutral ligands to the following phenomena: (1) anionic ligands pull FeIII further from the mean plane of a porphyrin than do neutral ligands, which will have the effect of straining the His-Fe bond in FeIII-2, and (2) heme in FeIII-2 is likely to undergo a modest doming distortion following anion binding that will render the His-ligated side of the porphyrin concave, thereby increasing porphyrin/ligand steric interactions. We propose that ruffling of the heme in FeIII-1 is an important factor contributing to its ability to resist His dissociation by weak-field anions. First, ruffling should allow His to more closely approach the porphyrin than is possible in FeIII-2, thereby reducing bond strain following anion binding. Second, the ruffling deformation in FeIII-1, which is enforced by the double covalent heme-peptide linkage, will almost certainly prevent significant porphyrin doming.
authors.affiliation: Department of Chemistry, University of Kansas, Lawrence, Kansas 66045, USA.
authors.forename: Aaron B
authors.initials: AB
authors.lastname: Cowley
authors.forename: David R
authors.initials: DR
authors.lastname: Benson
mesh_terms: D000818:Animals; D000838:Anions; D001386:Azides / Q000737:chemistry; D001665:Binding Sites; D003486:Cyanides / Q000737:chemistry; D045304:Cytochromes c / Q000737:chemistry / Q000378:metabolism; D005459:Fluorides / Q000737:chemistry; D006418:Heme / Q000138:chemical synthesis / Q000737:chemistry* / Q000378:metabolism; D006420:Hemeproteins / Q000737:chemistry*; D006639:Histidine / Q000737:chemistry*; D006736:Horses; D008024:Ligands; D015394:Molecular Structure; D009206:Myocardium / Q000201:enzymology; D010446:Peptide Fragments / Q000737:chemistry*; D010455:Peptides / Q000138:chemical synthesis* / Q000737:chemistry / Q000378:metabolism; D011487:Protein Conformation
chemical_list: D000838:Anions; D001386:Azides; D003486:Cyanides; D006420:Hemeproteins; D008024:Ligands; D010446:Peptide Fragments; D010455:Peptides; D006418:Heme; D006639:Histidine; D045304:Cytochromes c; C071067:N(alpha)-acetylmicroperoxidase-8; D005459:Fluorides