Crystal Structure of Rat Apo-Heme Oxygenase-1 (HO-1): Mechanism of Heme Binding in HO-1 Inferred from Structural Comparison of the Apo and Heme Complex Forms
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- 作者：Masakazu Sugishima ; Hiroshi Sakamoto ; Yoshimitsu Kakuta ; Yoshiaki Omata ; Shunsuke Hayashi ; Masato Noguchi ; and Keiichi Fukuyama
- 刊名：Biochemistry
- 出版年：2002
- 出版时间：June 11, 2002
- 年：2002
- 卷：41
- 期：23
- 页码：7293 - 7300
- 全文大小：769K
- 年卷期：v.41,no.23(June 11, 2002)
- ISSN：1520-4995
文摘
Heme oxygenase (HO) catalyzes the oxidative cleavage of heme to biliverdin by utilizing O2and 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 itscomplex with heme (HO-heme) showed three distinct differences. First, the A helix of the eight 
-helices(A-H) in HO-heme, which includes the proximal ligand of heme (His25), is invisible in apoHO. Inaddition, the B helix, a portion of which builds the heme pocket, is shifted toward the heme pocket inapoHO. Second, Gln38 is shifted toward the position where the -meso carbon of heme is located inHO-heme. N
of Gln38 is hydrogen-bonded to the carbonyl group of Glu29 located at the C-terminalside of the A helix in HO-heme, indicative that this hydrogen bond restrains the angle between the Aand B helices in HO-heme. Third, the amide group of Gly143 in the F helix is directed outward from theheme pocket in apoHO, whereas it is directed toward the distal ligand of heme in HO-heme. This meansthat the F helix around Gly143 must change its conformation to accommodate heme binding. The apoHOstructure has the characteristic that the helix on one side of the heme pocket fluctuates, whereas the restof the structure is similar to that of HO-heme, as observed in such hemoproteins as myoglobin andcytochromes b5 and b562. These structural features of apoHO suggest that the orientation of the proximalhelix and the position of His25 are fixed upon heme binding.
-helices(A-H) in HO-heme, which includes the proximal ligand of heme (His25), is invisible in apoHO. Inaddition, the B helix, a portion of which builds the heme pocket, is shifted toward the heme pocket inapoHO. Second, Gln38 is shifted toward the position where the -meso carbon of heme is located inHO-heme. N of Gln38 is hydrogen-bonded to the carbonyl group of Glu29 located at the C-terminalside of the A helix in HO-heme, indicative that this hydrogen bond restrains the angle between the Aand B helices in HO-heme. Third, the amide group of Gly143 in the F helix is directed outward from theheme pocket in apoHO, whereas it is directed toward the distal ligand of heme in HO-heme. This meansthat the F helix around Gly143 must change its conformation to accommodate heme binding. The apoHOstructure has the characteristic that the helix on one side of the heme pocket fluctuates, whereas the restof the structure is similar to that of HO-heme, as observed in such hemoproteins as myoglobin andcytochromes b5 and b562. These structural features of apoHO suggest that the orientation of the proximalhelix and the position of His25 are fixed upon heme binding.