Crystal structure of a UBP-family deubiquitinating enzyme in isolation and in complex with ubiquitin aldehyde.

Abstract:

: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.

journal_name

Cell

journal_title

Cell

authors

Hu M,Li P,Li M,Li W,Yao T,Wu JW,Gu W,Cohen RE,Shi Y

doi

10.1016/s0092-8674(02)01199-6

subject

Has Abstract

pub_date

2002-12-27 00:00:00

pages

1041-54

issue

7

eissn

0092-8674

issn

1097-4172

pii

S0092867402011996

journal_volume

111

pub_type

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