1r5x

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(New page: 200px<br /><applet load="1r5x" size="450" color="white" frame="true" align="right" spinBox="true" caption="1r5x, resolution 2.30&Aring;" /> '''JAMM: A Metalloprote...)
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[[Image:1r5x.gif|left|200px]]<br /><applet load="1r5x" size="450" color="white" frame="true" align="right" spinBox="true"
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[[Image:1r5x.gif|left|200px]]<br /><applet load="1r5x" size="350" color="white" frame="true" align="right" spinBox="true"
caption="1r5x, resolution 2.30&Aring;" />
caption="1r5x, resolution 2.30&Aring;" />
'''JAMM: A Metalloprotease-like Zinc Site in the Proteasome and Signalosome'''<br />
'''JAMM: A Metalloprotease-like Zinc Site in the Proteasome and Signalosome'''<br />
==Overview==
==Overview==
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The JAMM (JAB1/MPN/Mov34 metalloenzyme) motif in Rpn11 and Csn5 underlies, isopeptidase activities intrinsic to the proteasome and signalosome, respectively. We show here that the archaebacterial protein AfJAMM, possesses the key features of a zinc metalloprotease, yet with a distinct, fold. The histidine and aspartic acid of the conserved EX(n)HS/THX(7)SXXD, motif coordinate a zinc, whereas the glutamic acid hydrogen-bonds an aqua, ligand. By analogy to the active site of thermolysin, we predict that the, glutamic acid serves as an acid-base catalyst and the second serine, stabilizes a tetrahedral intermediate. Mutagenesis of Csn5 confirms these, residues are required for Nedd8 isopeptidase activity. The active, site-like architecture specified by the JAMM motif motivates, structure-based approaches to the study of JAMM domain proteins and the, development of therapeutic proteasome and signalosome inhibitors.
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The JAMM (JAB1/MPN/Mov34 metalloenzyme) motif in Rpn11 and Csn5 underlies isopeptidase activities intrinsic to the proteasome and signalosome, respectively. We show here that the archaebacterial protein AfJAMM possesses the key features of a zinc metalloprotease, yet with a distinct fold. The histidine and aspartic acid of the conserved EX(n)HS/THX(7)SXXD motif coordinate a zinc, whereas the glutamic acid hydrogen-bonds an aqua ligand. By analogy to the active site of thermolysin, we predict that the glutamic acid serves as an acid-base catalyst and the second serine stabilizes a tetrahedral intermediate. Mutagenesis of Csn5 confirms these residues are required for Nedd8 isopeptidase activity. The active site-like architecture specified by the JAMM motif motivates structure-based approaches to the study of JAMM domain proteins and the development of therapeutic proteasome and signalosome inhibitors.
==About this Structure==
==About this Structure==
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1R5X is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Archaeoglobus_fulgidus_dsm_4304 Archaeoglobus fulgidus dsm 4304] with ZN as [http://en.wikipedia.org/wiki/ligand ligand]. Full crystallographic information is available from [http://ispc.weizmann.ac.il/oca-bin/ocashort?id=1R5X OCA].
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1R5X is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Archaeoglobus_fulgidus_dsm_4304 Archaeoglobus fulgidus dsm 4304] with <scene name='pdbligand=ZN:'>ZN</scene> as [http://en.wikipedia.org/wiki/ligand ligand]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1R5X OCA].
==Reference==
==Reference==
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[[Category: Archaeoglobus fulgidus dsm 4304]]
[[Category: Archaeoglobus fulgidus dsm 4304]]
[[Category: Single protein]]
[[Category: Single protein]]
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[[Category: Ambroggio, X.I.]]
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[[Category: Ambroggio, X I.]]
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[[Category: Deshaies, R.J.]]
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[[Category: Deshaies, R J.]]
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[[Category: Rees, D.C.]]
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[[Category: Rees, D C.]]
[[Category: ZN]]
[[Category: ZN]]
[[Category: csn5]]
[[Category: csn5]]
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[[Category: structural genomics]]
[[Category: structural genomics]]
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''Page seeded by [http://ispc.weizmann.ac.il/oca OCA ] on Sat Nov 24 22:12:18 2007''
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 14:47:31 2008''

Revision as of 12:47, 21 February 2008

Image:1r5x.gif

1r5x, resolution 2.30Å

Drag the structure with the mouse to rotate

JAMM: A Metalloprotease-like Zinc Site in the Proteasome and Signalosome

Overview

The JAMM (JAB1/MPN/Mov34 metalloenzyme) motif in Rpn11 and Csn5 underlies isopeptidase activities intrinsic to the proteasome and signalosome, respectively. We show here that the archaebacterial protein AfJAMM possesses the key features of a zinc metalloprotease, yet with a distinct fold. The histidine and aspartic acid of the conserved EX(n)HS/THX(7)SXXD motif coordinate a zinc, whereas the glutamic acid hydrogen-bonds an aqua ligand. By analogy to the active site of thermolysin, we predict that the glutamic acid serves as an acid-base catalyst and the second serine stabilizes a tetrahedral intermediate. Mutagenesis of Csn5 confirms these residues are required for Nedd8 isopeptidase activity. The active site-like architecture specified by the JAMM motif motivates structure-based approaches to the study of JAMM domain proteins and the development of therapeutic proteasome and signalosome inhibitors.

About this Structure

1R5X is a Single protein structure of sequence from Archaeoglobus fulgidus dsm 4304 with as ligand. Full crystallographic information is available from OCA.

Reference

JAMM: a metalloprotease-like zinc site in the proteasome and signalosome., Ambroggio XI, Rees DC, Deshaies RJ, PLoS Biol. 2004 Jan;2(1):E2. Epub 2003 Nov 24. PMID:14737182

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