title: DFT analysis of axial and equatorial effects on heme-CO vibrational modes: applications to CooA and H-NOX heme sensor proteins.
abstract: Determinants of the Fe-CO and C-O stretching frequencies in (imidazole)heme-CO adducts have been investigated via density functional theory (DFT) analysis, in connection with puzzling characteristics of the heme sensor protein CooA and of the H-NOX (Heme-Nitric Oxide and/or OXygen binding) family of proteins, including soluble guanylate cyclase (sGC). The computations show that two mechanisms of Fe-histidine bond weakening have opposite effects on the nuFeC/nuCO pattern. Mechanical tension is expected to raise nuFeC with little change in nuCO whereas the weakening of H-bond donation from the imidazole ligand has the opposite effect. Data on CooA indicate imidazole H-bond weakening associated with heme displacement, as part of the activation mechanism. The computations also reveal that protein-induced distortion of the porphyrin ring, a prominent structural feature of the H-NOX protein TtTar4H (Thermoanaerobacter tengcongensis Tar4 protein heme domain), has surprisingly little effect on nuFeC or nuCO. However, another structural feature, strong H-bonding to the propionates, is suggested to account for the weakened back bonding that is evident in sGC. TtTar4H-CO itself has an elevated nuFeC, which is successfully modeled as a compression effect, resulting from steric crowding in the distal pocket. nuFeC/nuCO data, in conjunction with modeling, can provide valuable insight into mechanisms for heme-protein modulation.
authors.affiliation: Department of Chemistry, Princeton University, Princeton, New Jersey 08544, USA.
authors.forename: Changliang
authors.initials: C
authors.lastname: Xu
authors.forename: Mohammed
authors.initials: M
authors.lastname: Ibrahim
authors.forename: Thomas G
authors.initials: TG
authors.lastname: Spiro
mesh_terms: D001426:Bacterial Proteins / Q000737:chemistry; D015374:Biosensing Techniques; D002244:Carbon / Q000737:chemistry*; D002245:Carbon Dioxide / Q000737:chemistry*; D006418:Heme / Q000032:analysis* / Q000737:chemistry* / Q000378:metabolism; D006639:Histidine / Q000737:chemistry; D006860:Hydrogen Bonding; D007093:Imidazoles / Q000737:chemistry; D008954:Models, Biological; D008958:Models, Molecular; D008968:Molecular Conformation; D009569:Nitric Oxide / Q000737:chemistry* / Q000378:metabolism; D010087:Oxides / Q000737:chemistry; D010100:Oxygen / Q000737:chemistry* / Q000378:metabolism; D011166:Porphyrins / Q000737:chemistry; D011422:Propionates / Q000737:chemistry; D017510:Protein Folding; D011789:Quantum Theory; D046968:Thermoanaerobacter; D014732:Vibration
chemical_list: D001426:Bacterial Proteins; D007093:Imidazoles; D010087:Oxides; D011166:Porphyrins; D011422:Propionates; D002245:Carbon Dioxide; C041069:carboxyl radical; D009569:Nitric Oxide; D006418:Heme; D006639:Histidine; D002244:Carbon; C029899:imidazole; D010100:Oxygen