Defining the active site of cytochrome P-450: the crystal and molecular structure of an inhibitor, SKF-525A.
Defining the active site of cytochrome P-450: the crystal and molecular structure of an inhibitor, SKF-525A.
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定义细胞色素 P-450 的活性位点：抑制剂 SKF-525A 的晶体和分子结构。
DOI：
10.1093/carcin/8.7.881
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发表时间：
1987
期刊：
影响因子：
4.7
通讯作者：
Callahan,T
中科院分区：
文献类型：
--
作者：
Rossi,M;Markovitz,S;Callahan,T
报道了细胞色素P-450抑制剂SKF-525A[2-(二乙氨基)2，2-二苯基戊烯酸乙酯；盐酸丙二芬]的晶体和分子结构。盐酸普罗地芬是由空间群P21/c中的乙酸乙酯和醋酸混合物结晶而成，其中一个分子位于不对称单元中。晶胞常数β=109.41(1)°，晶胞常数面积=18.716(4)，b=8.906(1)，c=14.201(3)。使用直接方法求解结构，并将其精化为R值0.047；使用3757次反射加权R值为0.061。从晶体和分子结构可以看出，SKF-525A与可利用的酶有两种主要的互补相互作用模式：极性和非极性。主要涉及氯离子、季氮原子和羰基氧原子的极性相互作用。特别是，存在两个强氢键，一个是在氯之间。。。Hn，3.090(1)ä，另一个介于O2之间。。..H-C111(乙基氢原子之一)，3.411(2)；另一种是通过苯基和烷基的非极性相互作用。将盐酸普罗地芬与其他原子坐标可用的抑制剂进行比较，揭示了与其功能相关的共同特征。这些基团包括提供必要的分子间接触和主体的基团，如苯基和氢键受体，以及允许底物灵活性的四面体原子
The crystal and molecular structure of the cytochrome P-450 inhibitor, SKF-525A [2-(diethy1amino)ethyl 2,2diphenylpentenoate; proadifen hydrochloride] is described. Proadifen hydrochloride crystallized from an ethyl acetate and acetic acid mixture in the space group P21/cwith one molecule in the asymmetric unit. Cell constants area= 18.716(4),b= 8.906(1),c= 14.201(3), β = 109.41(1)°. The structure was solved using directmethods and was refined to anRvalue of 0.047; weightedRof 0.061 using 3757 reflections. From the crystal and molecular structure, it is seen that SKF-525A has two principal modes of complementary interactions with the enzyme available: polar and non-polar. Polar interactions that principally involve the chloride anion, the quaternary nitrogen atom and the carbonyl oxygen atom. In particular, there are two-strong hydrogen bonds, one between Cl . . . HN, 3.090(1) Å, the other between O2 . . ..H-C111 (one of the ethyl hydrogen atoms) at 3.411(2) Å. The other is thrortgh non-polar interactions involving the phenyl and alkyl groups. Comparisons between proadifen hydrochloride and other inhibitors whose atomic coordinates are available reveal common features which correlate with their function. These include groups to provide necessary intermolecular contacts and bulk, such as a pheyl group and a hydrogen bond acceptor, as well as a tetrahedral atom, which allows for substrate flexibility