Transition state analogue discrimination by related purine nucleoside phosphorylases.
Transition state analogue discrimination by related purine nucleoside phosphorylases.
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相关嘌呤核苷磷酸化酶对过渡态类似物的辨别。
DOI：
10.1021/ja061403n
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发表时间：
2006
影响因子：
15
通讯作者：
Schramm,VernL
中科院分区：
文献类型：
--
作者：
TaylorRingia,ErikaA;Tyler,PeterC;Evans,GaryB;Furneaux,RichardH;Murkin,AndrewS;Schramm,VernL
PNP的过渡态类似物Immucilins和DADMe− Immucilins被设计为分别匹配牛和人PNP的过渡态特征。具有或不具有底物的羟基和羟甲基基团的抑制剂证明，抑制剂几何形状模仿过渡态的几何形状赋予结合亲和力区分。这一发现是显着的，因为晶体学分析表明，在人类和牛的PNP的活性位点残基和接触配体的完全保守。
Transition state analogues of PNP, the Immucillins and DADMe−Immucillins, were designed to match transition state features of bovine and human PNPs, respectively. The inhibitors with or without the hydroxyl and hydroxymethyl groups of the substrate demonstrate that inhibitor geometry mimicking that of the transition state confers binding affinity discrimination. This finding is remarkable since crystallographic analysis indicates complete conservation of active site residues and contacts to ligands in human and bovine PNPs.