Quantum chemical calculations of the NHA bound nitric oxide synthase active site: O2 binding and implications for the catalytic mechanism.
Density functional theory has been employed to model the binding of the intermediate substrate NHA, by nitric oxide synthases. In particular, the orientation and interactions of possibly catalytically important substrate hydrogens, with and without molecular oxygen bound to the active site heme group, are considered. Without O(2), three possible conformers have been found, with the energetically most favored structure being that in which both protons of the -NHOH moiety of NHA are directed toward the heme group. With oxygen bound, four different structures were found. The energetically lowest structure is again found to have both hydrogens of the -NHOH group pointing toward the heme group, thus forming hydrogen bonds between -NH- and the terminal oxygen, and between -OH and the inner oxygen of the heme-O(2) group. In addition, unprotonated structures of the substrate bound to the active site are considered and the proton affinity calculated.
Contribution from the Department of Chemistry and Biochemistry, University of Windsor, Windsor, Ontario, N9B 3P4 Canada.
Kyung-Bin
KB
Cho
James W
JW
Gauld
D001120:Arginine / Q000031:analogs & derivatives* / Q000737:chemistry* / Q000378:metabolism*; D001665:Binding Sites; D002384:Catalysis; D003198:Computer Simulation; D008958:Models, Molecular; D019001:Nitric Oxide Synthase / Q000737:chemistry* / Q000378:metabolism*; D052247:Nitric Oxide Synthase Type II; D010100:Oxygen / Q000737:chemistry* / Q000378:metabolism*; D011487:Protein Conformation; D011522:Protons; D011789:Quantum Theory; D055672:Static Electricity; D013816:Thermodynamics
D011522:Protons; C068309:N(omega)-hydroxyarginine; D001120:Arginine; D019001:Nitric Oxide Synthase; D052247:Nitric Oxide Synthase Type II; D010100:Oxygen