2vfj
From Proteopedia
(New page: 200px<br /><applet load="2vfj" size="350" color="white" frame="true" align="right" spinBox="true" caption="2vfj, resolution 3.2Å" /> '''STRUCTURE OF THE A20 ...) |
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==Overview== | ==Overview== | ||
- | The NF-kappaB regulator A20 antagonises IKK activation by modulating | + | 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. |
==About this Structure== | ==About this Structure== | ||
- | 2VFJ is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] with <scene name='pdbligand=SO4:'>SO4</scene> and <scene name='pdbligand=MG:'>MG</scene> as [http://en.wikipedia.org/wiki/ligands ligands]. Active as [http://en.wikipedia.org/wiki/Ubiquitinyl_hydrolase_1 Ubiquitinyl hydrolase 1], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.4.19.12 3.4.19.12] Known structural/functional Sites: <scene name='pdbsite=AC1:So4 Binding Site For Chain C'>AC1</scene>, <scene name='pdbsite=AC2:So4 Binding Site For Chain D'>AC2</scene>, <scene name='pdbsite=AC3:So4 Binding Site For Chain C'>AC3</scene>, <scene name='pdbsite=AC4:So4 Binding Site For Chain D'>AC4</scene> and <scene name='pdbsite=AC5:Mg Binding Site For Chain D'>AC5</scene>. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2VFJ OCA]. | + | 2VFJ is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] with <scene name='pdbligand=SO4:'>SO4</scene> and <scene name='pdbligand=MG:'>MG</scene> as [http://en.wikipedia.org/wiki/ligands ligands]. Active as [http://en.wikipedia.org/wiki/Ubiquitinyl_hydrolase_1 Ubiquitinyl hydrolase 1], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.4.19.12 3.4.19.12] Known structural/functional Sites: <scene name='pdbsite=AC1:So4+Binding+Site+For+Chain+C'>AC1</scene>, <scene name='pdbsite=AC2:So4+Binding+Site+For+Chain+D'>AC2</scene>, <scene name='pdbsite=AC3:So4+Binding+Site+For+Chain+C'>AC3</scene>, <scene name='pdbsite=AC4:So4+Binding+Site+For+Chain+D'>AC4</scene> and <scene name='pdbsite=AC5:Mg+Binding+Site+For+Chain+D'>AC5</scene>. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2VFJ OCA]. |
==Reference== | ==Reference== | ||
- | Structure of the A20 OTU domain and mechanistic insights into deubiquitination., Komander D, Barford D, Biochem J. | + | Structure of the A20 OTU domain and mechanistic insights into deubiquitination., Komander D, Barford D, Biochem J. 2008 Jan 1;409(1):77-85. PMID:[http://ispc.weizmann.ac.il//pmbin/getpm?pmid=17961127 17961127] |
[[Category: Homo sapiens]] | [[Category: Homo sapiens]] | ||
[[Category: Single protein]] | [[Category: Single protein]] | ||
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[[Category: zinc-finger]] | [[Category: zinc-finger]] | ||
- | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 18:55:35 2008'' |
Revision as of 16:55, 21 February 2008
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STRUCTURE OF THE A20 OVARIAN TUMOUR (OTU) DOMAIN
Overview
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.
About this Structure
2VFJ is a Single protein structure of sequence from Homo sapiens with and as ligands. Active as Ubiquitinyl hydrolase 1, with EC number 3.4.19.12 Known structural/functional Sites: , , , and . Full crystallographic information is available from OCA.
Reference
Structure of the A20 OTU domain and mechanistic insights into deubiquitination., Komander D, Barford D, Biochem J. 2008 Jan 1;409(1):77-85. PMID:17961127
Page seeded by OCA on Thu Feb 21 18:55:35 2008
Categories: Homo sapiens | Single protein | Ubiquitinyl hydrolase 1 | Barford, D. | Komander, D. | MG | SO4 | Apoptosis | Cysteine protease | Cytokine signalling | Cytoplasm | Deubiquitinating enzyme | Dna-binding | Hydrolase | Lys63- linked | Metal-binding | Nf-kb | Nucleus | Otu | Ovarian tumour | Phosphorylation | Polymorphism | Protease | Thiol protease | Ubiquitin | Ubl conjugation pathway | Zinc | Zinc-finger