Azide-inhibited bacterial heme oxygenases exhibit an S = 3/2 (dxz,dyz)3(dxy)1(dz2)1 spin state: mechanistic implications for heme oxidation.
The azide complexes of heme oxygenase from Pseudomonas aeruginosa (pa-HO) and Neisseriae meningitidis (nm-HO) have been studied with the aid of (1)H and (13)C NMR spectroscopy. These complexes have been shown to exist as an equilibrium mixture of two populations, one exhibiting an S = (1)/(2), (d(xy))(2)(d(xz), d(yz))(3) electron configuration and planar heme and a second with a novel S = (3)/(2), (d(xz), d(yz))(3)(d(xy))(1)(d(z)(2))(1) spin state and nonplanar heme. At physiologically relevant temperatures, the equilibrium shifts in the direction of the population exhibiting the latter electron configuration and nonplanar heme, whereas at temperatures approaching the freezing point of water, the equilibrium shifts in the direction of the population with the former electronic structure and planar heme. These findings indicate that the microenvironment of the distal pocket in heme oxygenase is unique among heme-containing proteins in that it lowers the sigma-donating (field strength) ability of the distal ligand and, therefore, promotes the attainment of heme electronic structures thus far only observed in heme oxygenase. When the field strength of the distal ligand is slightly lower than that of azide, such as OH(-) (J. Am. Chem. Soc. 2003, 125, 11842), the corresponding complex exists as a mixture of populations with nonplanar hemes and electronic structures that place significant spin density at the meso positions. The ease with which these unusual heme electronic structures are attained by heme oxygenase is likely related to activation of meso carbon reactivity which, in turn, facilitates hydroxylation of a meso carbon by the obligatory ferric hydroperoxide intermediate.
Zeng
Yuhong
Y
Department of Chemistry, The University of Kansas, Lawrence, Kansas 66045-7582, USA.
Caignan
Gregori A
GA
Bunce
Richard A
RA
Rodríguez
Juan Carlos
JC
Wilks
Angela
A
Rivera
Mario
M
D000042:Absorption; D001386:Azides / Q000494:pharmacology*; D006418:Heme / Q000737:chemistry* / Q000378:metabolism*; D006419:Heme Oxygenase (Decyclizing) / Q000037:antagonists & inhibitors* / Q000378:metabolism*; D008665:Metalloporphyrins; D015394:Molecular Structure; D009345:Neisseria meningitidis / Q000201:enzymology*; D010084:Oxidation-Reduction / Q000187:drug effects; D011166:Porphyrins / Q000737:chemistry; D011550:Pseudomonas aeruginosa / Q000201:enzymology*; D013057:Spectrum Analysis
D001386:Azides; D008665:Metalloporphyrins; D011166:Porphyrins; D006418:Heme; D006419:Heme Oxygenase (Decyclizing)