Structural basis for the specificity of ubiquitin C-terminal hydrolases
Structural basis for the specificity of ubiquitin C-terminal hydrolases
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DOI：
10.1093/emboj/18.14.3877
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发表时间：
1999-07-15
期刊：
影响因子：
11.4
通讯作者：
Hill, CP
中科院分区：
文献类型：
--
作者：
Johnston, SC;Riddle, SM;Hill, CP
泛素从与其他蛋白质和加合物的连接中释放对于泛素生物合成、蛋白酶体降解和其他细胞过程至关重要。去泛素化部分由UCH（泛素C-末端水解酶）家族的成员完成。我们已经确定了酵母UGH，Yuhl的2.25埃分辨率晶体结构，在与抑制剂泛素醛（Ubal）的复合物中，该结构模拟反应途径中的四面体中间体，并解释了非常高的酶特异性，与相关的比较，未配体的UCH结构表明泛素结合与重排偶联，在没有真实底物的情况下，位点分裂。值得注意的是，在结合Ubal后变得有序的21个残基环直接位于活性位点上，有效处理的底物显然通过该环，并且对环构象的限制可能起到控制UCH特异性的作用。
The release of ubiquitin from attachment to other proteins and adducts is critical for ubiquitin biosynthesis, proteasomal degradation and other cellular processes, De-ubiquitination is accomplished in part by members of the UCH (ubiquitin C-terminal hydrolase) family of enzymes. We have determined the 2.25 Angstrom resolution crystal structure of the yeast UGH, Yuhl, in a complex with the inhibitor ubiquitin aldehyde (Ubal), The structure mimics the tetrahedral intermediate in the reaction pathway and explains the very high enzyme specificity, Comparison with a related, unliganded UCH structure indicates that ubiquitin binding is coupled to rearrangements which block the active-site cleft in the absence of authentic substrate. Remarkably, a 21-residue loop that becomes ordered upon binding Ubal lies directly over the active site, Efficiently processed substrates apparently pass through this loop, and constraints on the loop conformation probably function to control UCH specificity.