STRUCTURE AND FUNCTION OF CYTOCHROMES-P450 - A COMPARATIVE-ANALYSIS OF 3 CRYSTAL-STRUCTURES
STRUCTURE AND FUNCTION OF CYTOCHROMES-P450 - A COMPARATIVE-ANALYSIS OF 3 CRYSTAL-STRUCTURES
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DOI：
10.1016/s0969-2126(01)00134-4
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发表时间：
1995-01-15
期刊：
影响因子：
5.7
通讯作者：
DEISENHOFER, J
中科院分区：
文献类型：
--
作者：
HASEMANN, CA;KURUMBAIL, RG;DEISENHOFER, J
背景：细胞色素P450催化多种疏水底物的氧化。P450家族之间的序列同一性通常较低（10-30%），因此，P450之间的结构-功能相关性尚不清楚。最近测定了P450（terp）和P450的血红素蛋白结构域（BM-3）的晶体结构，并与已有的P450（cam）结构进行了比较。血红素结合的核心结构是保守的，除了局部差异的I螺旋。在底物结合区观察到最大的变化。蛋白质的结构叠加允许其他P450的改进的序列比对。在这三种结构中的电荷分布同样是不对称的，并定义了一个分子dipole.Conclusions：基于这种比较，我们相信，所有的P450将被发现具有相同的三级结构。精确预测其他P450底物接触残基的能力受到底物识别区域极端结构异质性的限制。P450（terp）和P45 O（BM-3）的中心I-螺旋结构表明螺旋相关溶剂分子作为催化质子来源的作用，与P450（cam）的机制不同。我们认为P450的P450分子偶极可能有助于氧化还原伴侣对接和催化质子补充。
Background: Cytochromes P450 catalyze the oxidation of a variety of hydrophobic substrates. Sequence identities between P450 families are generally low (10-30%), and consequently, the structure-function correlations among P450s are not clear. The crystal structures of P450(terp) and the hemoprotein domain of P450(BM-3) were recently determined, and are compared here with the previously available structure of P450(cam).Results: The topology of all three enzymes is quite similar. The heme-binding core structure is well conserved, except for local differences in the I helices. The greatest variation is observed in the substrate-binding regions. The structural superposition of the proteins permits an improved sequence alignment of other P450s. The charge distribution in the three structures is similarly asymmetric and defines a molecular dipole.Conclusions: Based on this comparison we believe that all P450s will be found to possess the same tertiary structure. The ability to precisely predict other P450 substratecontact residues is limited by the extreme structural heterogeneity in the substrate-recognition regions. The central I-helix structures of P450(terp) and P45O(BM-3) suggest a role for helix-associated solvent molecules as a source of catalytic protons, distinct from the mechanism for P450(cam). We suggest that the P450 molecular dipole for P450 might aid in both redox-partner docking and proton recruitment for catalysis.