title: Quantum chemical evaluation of protein control over heme ligation: CO/O2 discrimination in myoglobin.
abstract: Control of O2 versus CO binding in myoglobin (Mb) is tuned by a distal histidine residue through steric and H-bonding interactions. These interactions have been evaluated via Car-Parrinello DFT calculations, whose efficiency allows full quantum mechanical treatment of the 13 closest residues surrounding the heme. The small (8 degrees ) deviation of the Fe-C-O bond angle from linearity results from the steric influence of a distal valine residue and not the distal histidine. H-bond energies were evaluated by replacing the distal histidine with the non-H-bonding residue isoleucine. Binding energies for CO and O2 decreased by 0.8 and 4.1 kcal/mol for MbCO and MbO2, in good agreement with experimental H-bond estimates. Ligand discrimination is dominated by distal histidine H-bonding, which is also found to stabilize a metastable side-on isomer of MbO2 that may play a key role in MbO2 photodynamics.
authors.affiliation: Chemistry Department, Princeton University, Princeton, New Jersey 08544, USA.
authors.forename: Filippo
authors.initials: F
authors.lastname: De Angelis
authors.forename: Andrzej A
authors.initials: AA
authors.lastname: Jarzecki
authors.forename: Roberto
authors.initials: R
authors.lastname: Car
authors.forename: Thomas G
authors.initials: TG
authors.lastname: Spiro
mesh_terms: D000818:Animals; D001665:Binding Sites; D002244:Carbon / Q000737:chemistry; D002248:Carbon Monoxide / Q000737:chemistry*; D006418:Heme / Q000737:chemistry*; D006639:Histidine / Q000737:chemistry; D007532:Isoleucine / Q000737:chemistry; D008958:Models, Molecular; D008968:Molecular Conformation; D009211:Myoglobin / Q000737:chemistry*; D010100:Oxygen / Q000737:chemistry*; D010777:Photochemistry / Q000379:methods; D011485:Protein Binding; D011789:Quantum Theory; D012984:Software
chemical_list: D009211:Myoglobin; D007532:Isoleucine; D006418:Heme; D006639:Histidine; D002244:Carbon; D002248:Carbon Monoxide; D010100:Oxygen