Crystal Structure of Rat Heme Oxygenase-1 in Complex with Biliverdin-Iron Chelate
Crystal Structure of Rat Heme Oxygenase-1 in Complex with Biliverdin-Iron Chelate
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DOI：
10.1074/jbc.m303682200
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发表时间：
2003-08
影响因子：
4.8
通讯作者：
M. Sugishima;H. Sakamoto;Y. Higashimoto;M. Noguchi;K. Fukuyama
中科院分区：
文献类型：
--
作者：
M. Sugishima;H. Sakamoto;Y. Higashimoto;M. Noguchi;K. Fukuyama
大鼠血红素氧合酶-1与胆汁素-铁螯合物（胆汁素(Fe)-HO-1）的结晶体结构，最终产物胆汁素的直接前体，已在2.4-Å分辨率下测定。血红素口袋中的电子密度清楚地表明血红素的四吡咯环在α-中位边缘被切割。与与HO-1结合的血红素一样，胆绿素-铁螯合物位于远端和近端螺旋之间，但由于溶剂暴露的丙酸基团和乙烯基的无序性，其调节状态似乎不太稳定。在胆绿素(Fe)-HO-1中，远端螺旋的中间从活性部位的中心移位，增加了血红素口袋的大小。glu29和Gln-38之间的氢键相互作用被认为是抑制血红素-HO-1络合物中近端螺旋的方向，但在胆绿素(Fe)-HO-1中失去了，导致螺旋松弛。胆绿素具有扭曲的螺旋构象；其吡咯环a的内酰胺氧原子通过氢键溶剂网络与Asp-140相互作用。由于缺乏远端水配体，铁原子与His-25和四个吡咯氮原子五配位。配位几何很大程度上偏离了方形金字塔，这表明铁可能很容易解离。我们推测血红素口袋的开放构象促进了顺序产物的释放，首先是铁，然后是胆绿素，并且由于胆绿素的灵活性增加，铁的释放触发了其缓慢的解离。
The crystal structure of rat heme oxygenase-1 in complex with biliverdin-iron chelate (biliverdin(Fe)-HO-1), the immediate precursor of the final product, biliverdin, has been determined at a 2.4-Å resolution. The electron density in the heme pocket clearly showed that the tetrapyrrole ring of heme is cleaved at the α-meso edge. Like the heme bound to HO-1, biliverdin-iron chelate is located between the distal and proximal helices, but its accommodation state seems to be less stable in light of the disordering of the solvent-exposed propionate and vinyl groups. The middle of the distal helix is shifted away from the center of the active site in biliverdin(Fe)-HO-1, increasing the size of the heme pocket. The hydrogen-bonding interaction between Glu-29 and Gln-38, considered to restrain the orientation of the proximal helix in the heme-HO-1 complex, was lost in biliverdin(Fe)-HO-1, leading to relaxation of the helix. Biliverdin has a distorted helical conformation; the lactam oxygen atom of its pyrrole ring-A interacted with Asp-140 through a hydrogen-bonding solvent network. Because of the absence of a distal water ligand, the iron atom is five-coordinated with His-25 and four pyrrole nitrogen atoms. The coordination geometry deviates considerably from a square pyramid, suggesting that the iron may be readily dissociated. We speculate that the opened conformation of the heme pocket facilitates sequential product release, first iron then biliverdin, and that because of biliverdin's increased flexibility, iron release triggers its slow dissociation.