Crystal structure of the human adenovirus proteinase with its 11 amino acid cofactor
Crystal structure of the human adenovirus proteinase with its 11 amino acid cofactor
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DOI：
10.1002/j.1460-2075.1996.tb00526.x
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发表时间：
1996-04-15
期刊：
影响因子：
11.4
通讯作者：
Mangel, WF
中科院分区：
文献类型：
--
作者：
Ding, JZ;McGrath, WJ;Mangel, WF
通过 X 射线晶体分析以 2.6 埃分辨率测定了与其 11 个氨基酸辅因子 pVIc 复合的人腺病毒 2 蛋白酶的三维结构。这种蛋白质的折叠以前从未见过。然而，它代表了微妙分歧或强烈趋同进化的一个例子，因为活性位点包含半胱氨酸-组氨酸-谷氨酸三联体和氧阴离子孔，其排列与木瓜蛋白酶类似。因此，腺病毒蛋白酶代表了第五组新的酶，含有催化三联体，pVIc，它在主链中延伸了β-折叠，远离活性位点，但它的结合使底物水解的催化速率常数增加了300倍。该结构揭示了抗病毒治疗的几个潜在靶点。
The three-dimensional structure of the human adenovirus-2 proteinase complexed with its 11 amino acid cofactor, pVIc, was determined at 2.6 Angstrom resolution by X-ray crystallographic analysis. The fold of this protein has not been seen before. However, it represents an example of either subtly divergent or powerfully convergent evolution, because the active site contains a Cys-His-Glu triplet and oxyanion hole in an arrangement similar to that in papain. Thus, the adenovirus proteinase represents a new, fifth group of enzymes that contain catalytic triads, pVIc, which extends a beta-sheet in the main chain, is distant from the active site, yet its binding increases the catalytic rate constant 300-fold for substrate hydrolysis. The structure reveals several potential targets for antiviral therapy.