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Crystal structure of human otubain 2
Max H Nanao1, Sergey O Tcherniuk, Jadwiga Chroboczek
1Laboratoire de Cristallographie Macromoléculaire, Institut de Biologie Structurale JP Ebel (CEA/CNRS/UJF), 41 rue Jules Horowitz, 38027 Grenoble, France.
EMBO Reports
|July 20, 2004
Summary
Researchers reveal the novel structure of otubain 2, a deubiquitylating enzyme (DUB). This unique fold and active site explain otubain 2's specific substrate interactions and low activity in protein ubiquitylation regulation.
Area of Science:
- Structural Biology
- Biochemistry
- Molecular Biology
Background:
- Ubiquitylation is a key post-translational modification regulating numerous cellular processes.
- Deubiquitylating enzymes (DUBs) reverse ubiquitylation, controlling protein function.
- Otubains, a family of DUBs within the OTU superfamily, play crucial roles in cellular regulation.
Purpose of the Study:
- To determine the crystal structure of otubain 2, an OTU superfamily deubiquitylating enzyme.
- To elucidate the structural basis for otubain 2's enzymatic activity and substrate specificity.
Main Methods:
- X-ray crystallography was employed to determine the 2.1 Å resolution structure of otubain 2.
- Comparative analysis with other DUB structures was performed to model otubain-ubiquitin binding.
Main Results:
- The crystal structure reveals a novel fold for deubiquitylating enzymes within the ovarian tumour (OTU) superfamily.
- Otubain 2 possesses a unique active-site cleft occlusion by a novel loop conformation.
- The oxyanion hole is uniquely formed by backbone amides, and distinct residues stabilize the active-site histidine.
Conclusions:
- The novel structural features of otubain 2, including its active-site topology, provide insights into its low turnover rate and substrate specificity.
- This structural understanding is crucial for deciphering the regulatory mechanisms of ubiquitylation by otubain family DUBs.