A PROTEIN CATALYTIC FRAMEWORK WITH AN N-TERMINAL NUCLEOPHILE IS CAPABLE OF SELF-ACTIVATION
A PROTEIN CATALYTIC FRAMEWORK WITH AN N-TERMINAL NUCLEOPHILE IS CAPABLE OF SELF-ACTIVATION
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DOI：
10.1038/378416a0
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发表时间：
1995-11-23
期刊：
影响因子：
64.8
通讯作者：
MURZIN, AG
中科院分区：
文献类型：
--
作者：
BRANNIGAN, JA;DODSON, G;MURZIN, AG
最近测定了三种氨基水解酶的晶体结构(1-3)：谷氨酰胺PRPP氨基转移酶(GAT)、青霉素酰化酶和蛋白酶体。这些酶使用氨基末端残基的侧链，结合在β-折叠中，作为亲核剂催化攻击羰基碳。GAT中的亲核物质是半胱氨酸，青霉素酰化酶中的是丝氨酸，蛋白酶体中的是苏氨酸。在这里，我们证明了所有三种酶都有一个不寻常的折叠，其中亲核基和其他催化基团占据了相同的位置。这种折叠既提供了亲核攻击的能力，也提供了自催化处理的可能性。我们建议将这个结构超家族的酶命名为NTN(N-末端亲核试剂)水解酶，这些酶似乎在进化上是相关的，但它们的分歧超出了任何可识别的序列相似性。
THE crystal structures of three amidohydrolases have been determined recently(1-3): glutamine PRPP amidotransferase (GAT), penicillin acylase, and the proteasome. These enzymes use the side chain of the amino-terminal residue, incorporated in a beta-sheet, as the nucleophile in the catalytic attack at the carbonyl carbon. The nucleophile is cysteine in GAT, serine in penicillin acylase, and threonine in the proteasome. Here we show that all three enzymes share an unusual fold in which the nucleophile and other catalytic groups occupy equivalent sites. This fold provides both the capacity for nucleophilic attack and the possibility of autocatalytic processing. We suggest the name Ntn (N-terminal nucleophile) hydrolases for this structural superfamily of enzymes which appear to be evolutionarily related but which have diverged beyond any recognizable sequence similarity.