Heme oxygenase (HO) catalyzes the oxidative cleavage of heme to biliverdin by utilizing O2 and NADPH. HO (apoHO) was crystallized as twinned P32 with three molecules per asymmetric unit, and its crystal structure was determined at 2.55 Å resolution. Structural comparison of apoHO and its complex with heme (HO-heme) showed three distinct differences. First, the A helix of the eight α-helices (A-H) in HO-heme, which includes the proximal ligand of heme (His25), is invisible in apoHO. In addition, the B helix, a portion of which builds the heme pocket, is shifted toward the heme pocket in apoHO. Second, Gln38 is shifted toward the position where the α-meso carbon of heme is located in HO-heme. Nε of Gln38 is hydrogen-bonded to the carbonyl group of Glu29 located at the C-terminal side of the A helix in HO-heme, indicative that this hydrogen bond restrains the angle between the A and B helices in HO-heme. Third, the amide group of Gly143 in the F helix is directed outward from the heme pocket in apoHO, whereas it is directed toward the distal ligand of heme in HO-heme. This means that the F helix around Gly143 must change its conformation to accommodate heme binding. The apoHO structure has the characteristic that the helix on one side of the heme pocket fluctuates, whereas the rest of the structure is similar to that of HO-heme, as observed in such hemoproteins as myoglobin and cytochromes b5 and b562. These structural features of apoHO suggest that the orientation of the proximal helix and the position of His25 are fixed upon heme binding.
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