Molecular mechanism of heme degradation catalyzed by heme oxygenase

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(1) We observed the resonance Raman spectra for alpha-hydroxyheme and verdoheme complexes of heme oxygensae (HO). We found that the ferric alpha-hydroxyheme and ferrous verdoheme complexes showed atypical Raman patterns, which are interpreted. as the result of the symmnetry lowering of the porphyrin-conjugating pi-electron system.(2) previously we found that histidine residue of HO was the proximal lignd of heme. To identify the axial heme lignd of HO-2, we prepared His45 to Ala (H45A) and His152 to Ala (H152A) mutants. H45A could form a 1 : 1 complex with hemin but was completely devoid of the heme degradation activity. A 5-coordinate-type ferrous NO EPR spectrum was observed for the heme-H45A complex. On the contrary, H152A mutant exhibited spectroscopic and enzymatic properties identical to those of wild-type. His132 of HO-1, Which corresponds to His152 of HO-2, was also not important for the heme degradation activity.(3) The O_2 and CO reactions with the heme, alpha-hydroxyheme, and veroheme complexes of HO were studied. The heme complexs of HO-1 and HO-2 have similar O_2 and CO binding properties. The O_2 affinities for heme and hydroxyheme・are very high, but the CO affinities are only 1-6-fold higher than the O_2 affinities. Thus, HO discriminate much more strongly against CO binding than myoglobin. The CO affinities of the verdoheme complex are about 10,000 times weaker than those of the heme complex. The positive charge on the verdoporphyrin ring causes a large decrease in reactivity of the iron.