2vfj

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(New page: 200px<br /><applet load="2vfj" size="350" color="white" frame="true" align="right" spinBox="true" caption="2vfj, resolution 3.2&Aring;" /> '''STRUCTURE OF THE A20 ...)
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==Overview==
==Overview==
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The NF-kappaB regulator A20 antagonises IKK activation by modulating, Lys63-linked polyubiquitination of cytokine receptor associated factors, including TRAF2/6 and RIP1. Here we describe the crystal structure of the, N-terminal Ovarian Tumour (OTU) 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. 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.
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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==
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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].
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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==
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Structure of the A20 OTU domain and mechanistic insights into deubiquitination., Komander D, Barford D, Biochem J. 2007 Oct 26;. PMID:[http://ispc.weizmann.ac.il//pmbin/getpm?pmid=17961127 17961127]
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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]]
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Wed Jan 23 11:53:28 2008''
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''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


2vfj, resolution 3.2Å

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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

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