Crystal structure of a UBP-family deubiquitinating enzyme in isolation and in complex with ubiquitin aldehyde
Crystal structure of a UBP-family deubiquitinating enzyme in isolation and in complex with ubiquitin aldehyde
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DOI：
10.1016/s0092-8674(02)01199-6
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发表时间：
2002-12-27
期刊：
影响因子：
64.5
通讯作者：
Shi, YG
中科院分区：
文献类型：
--
作者：
Hu, M;Li, PW;Shi, YG
泛素特异性加工蛋白酶（UBP）家族的去泛素化酶在许多细胞过程中起着至关重要的作用。HAUSP，一种代表性的UBP，特异性地去泛素化，从而稳定肿瘤抑制蛋白p53。在这里，我们报告的晶体结构的40 kDa的催化核心结构域的HAUSP在隔离和复杂的泛素醛。这些研究表明，UBP去泛素化酶表现出保守的三个结构域的架构，包括手指，手掌，和拇指。离开的泛素部分由手指特异性地配位，其C末端位于手掌和拇指之间的活性位点。泛素醛的结合诱导活性位点的剧烈构象变化，重新排列催化三联体残基进行催化。
The ubiquitin-specific processing protease (UBP) family of deubiquitinating enzymes plays an essential role in numerous cellular processes. HAUSP, a representative UBP, specifically deubiquitinates and hence stabilizes the tumor suppressor protein p53. Here, we report the crystal structures of the 40 kDa catalytic core domain of HAUSP in isolation and in complex with ubiquitin aldehyde. These studies reveal that the UBP deubiquitinating enzymes exhibit a conserved three-domain architecture, comprising Fingers, Palm, and Thumb. The leaving ubiquitin moiety is specifically coordinated by the Fingers, with its C terminus placed in the active site between the Palm and the Thumb. Binding by ubiquitin aldehyde induces a drastic conformational change in the active site that realigns the catalytic triad residues for catalysis.