Brannigan J A, Dodson G, Duggleby H J, Moody P C, Smith J L, Tomchick D R, Murzin A G
Chemistry Department, University of York, UK.
Nature. 1995 Nov 23;378(6555):416-9. doi: 10.1038/378416a0.
The crystal structures of three amidohydrolases have been determined recently: 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.
谷氨酰胺磷酸核糖焦磷酸酰胺转移酶（GAT）、青霉素酰化酶和蛋白酶体。这些酶将位于β-折叠中的氨基末端残基的侧链用作亲核试剂，对羰基碳进行催化攻击。亲核试剂在GAT中是半胱氨酸，在青霉素酰化酶中是丝氨酸，在蛋白酶体中是苏氨酸。在此我们表明，这三种酶都具有一种不寻常的折叠结构，其中亲核试剂和其他催化基团占据等效位点。这种折叠结构既提供了亲核攻击的能力，也提供了自催化加工的可能性。我们建议将这个酶的结构超家族命名为Ntn（氨基末端亲核试剂）水解酶，它们似乎在进化上相关，但已分化到没有任何可识别的序列相似性。
