2VFJ

Structure of the A20 Ovarian Tumour (OTU) domain

Summary for 2VFJ

• Entry DOI: 10.2210/pdb2vfj/pdb
• Descriptor: TUMOR NECROSIS FACTOR, SULFATE ION, MAGNESIUM ION (3 entities in total)
• Functional Keywords: phosphorylation, cysteine protease, metal-binding, ovarian tumour, thiol protease, dna-binding, polymorphism, lys63-linked, hydrolase, cytoplasm, ubiquitin, zinc-finger, deubiquitinating enzyme, cytokine signalling, ubl conjugation pathway, otu, zinc, nf-kb, nucleus, protease, apoptosis
• Biological source: HOMO SAPIENS (HUMAN)
• Cellular location: Cytoplasm: P21580
• Total number of polymer chains: 4
• Total formula weight: 172822.48

Authors

Komander, D.,Barford, D. (deposition date: 2007-11-04, release date: 2007-12-04, Last modification date: 2024-05-08)

Primary citation

Komander, D.,Barford, D.
Structure of the A20 Otu Domain and Mechanistic Insights Into Deubiquitination
Biochem.J., 409:77-, 2008

PubMed Abstract: The NF-kappaB (nuclear factor kappaB) regulator A20 antagonises IKK [IkappaB (inhibitor of kappaB) kinase] activation by modulating Lys63-linked polyubiquitination of cytokine-receptor-associated factors including TRAF2/6 (tumour-necrosis-factor-receptor-associated factor 2/6) and RIP1 (receptor-interacting protein 1). In the present paper we describe the crystal structure of the N-terminal OTU (ovarian tumour) deubiquitinase domain of A20, which differs from other deubiquitinases but shares the minimal catalytic core with otubain-2. Analysis of conserved surface regions allows prediction of ubiquitin-binding sites for the proximal and distal ubiquitin molecules. Structural and biochemical analysis suggests a novel architecture of the catalytic triad, which might be present in a subset of OTU domains including Cezanne and TRABID (TRAF-binding domain). Biochemical analysis shows a preference of the isolated A20 OTU domain for Lys48-linked tetraubiquitin in vitro suggesting that additional specificity factors might be required for the physiological function of A20 in cells.

PubMed: 17961127
DOI: 10.1042/BJ20071399

Experimental method

X-RAY DIFFRACTION (3.2 Å)