1jd2
From Proteopedia
(New page: 200px<br /><applet load="1jd2" size="450" color="white" frame="true" align="right" spinBox="true" caption="1jd2, resolution 3.0Å" /> '''Crystal Structure of ...) |
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| - | [[Image:1jd2.gif|left|200px]]<br /><applet load="1jd2" size=" | + | [[Image:1jd2.gif|left|200px]]<br /><applet load="1jd2" size="350" color="white" frame="true" align="right" spinBox="true" |
caption="1jd2, resolution 3.0Å" /> | caption="1jd2, resolution 3.0Å" /> | ||
'''Crystal Structure of the yeast 20S Proteasome:TMC-95A complex: A non-covalent Proteasome Inhibitor'''<br /> | '''Crystal Structure of the yeast 20S Proteasome:TMC-95A complex: A non-covalent Proteasome Inhibitor'''<br /> | ||
==Overview== | ==Overview== | ||
| - | The 20 S proteasome core particle (CP), a multicatalytic protease, is | + | The 20 S proteasome core particle (CP), a multicatalytic protease, is involved in a variety of biologically important processes, including immune response, cell-cycle control, metabolic adaptation, stress response and cell differentiation. Therefore, selective inhibition of the CP will be one possible way to influence these essential pathways. Recently, a new class of specific proteasome inhibitors, TMC-95s, was investigated and we now present a biochemical and crystallographic characterisation of the yeast proteasome core particle in complex with the natural product TMC-95A. This unusual heterocyclic compound specifically blocks the active sites of CPs non-covalently, without modifying the nucleophilic Thr1 residue. The inhibitor is bound to the CP by specific hydrogen bonds with the main-chain atoms of the protein. Analysis of the crystal structure of the complex has revealed which portions of TMC-95s are essential for binding to the proteasome. This will form the basis for the development of synthetic selective proteasome inhibitors as promising candidates for anti-tumoral or anti-inflammatory drugs. |
==About this Structure== | ==About this Structure== | ||
| - | 1JD2 is a [http://en.wikipedia.org/wiki/Protein_complex Protein complex] structure of sequences from [http://en.wikipedia.org/wiki/Saccharomyces_cerevisiae Saccharomyces cerevisiae] with MG and 95A as [http://en.wikipedia.org/wiki/ligands ligands]. Active as [http://en.wikipedia.org/wiki/Proteasome_endopeptidase_complex Proteasome endopeptidase complex], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.4.25.1 3.4.25.1] Full crystallographic information is available from [http:// | + | 1JD2 is a [http://en.wikipedia.org/wiki/Protein_complex Protein complex] structure of sequences from [http://en.wikipedia.org/wiki/Saccharomyces_cerevisiae Saccharomyces cerevisiae] with <scene name='pdbligand=MG:'>MG</scene> and <scene name='pdbligand=95A:'>95A</scene> as [http://en.wikipedia.org/wiki/ligands ligands]. Active as [http://en.wikipedia.org/wiki/Proteasome_endopeptidase_complex Proteasome endopeptidase complex], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.4.25.1 3.4.25.1] Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1JD2 OCA]. |
==Reference== | ==Reference== | ||
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[[Category: proteasome:inhibitor complex]] | [[Category: proteasome:inhibitor complex]] | ||
| - | ''Page seeded by [http:// | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 13:21:17 2008'' |
Revision as of 11:21, 21 February 2008
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Crystal Structure of the yeast 20S Proteasome:TMC-95A complex: A non-covalent Proteasome Inhibitor
Overview
The 20 S proteasome core particle (CP), a multicatalytic protease, is involved in a variety of biologically important processes, including immune response, cell-cycle control, metabolic adaptation, stress response and cell differentiation. Therefore, selective inhibition of the CP will be one possible way to influence these essential pathways. Recently, a new class of specific proteasome inhibitors, TMC-95s, was investigated and we now present a biochemical and crystallographic characterisation of the yeast proteasome core particle in complex with the natural product TMC-95A. This unusual heterocyclic compound specifically blocks the active sites of CPs non-covalently, without modifying the nucleophilic Thr1 residue. The inhibitor is bound to the CP by specific hydrogen bonds with the main-chain atoms of the protein. Analysis of the crystal structure of the complex has revealed which portions of TMC-95s are essential for binding to the proteasome. This will form the basis for the development of synthetic selective proteasome inhibitors as promising candidates for anti-tumoral or anti-inflammatory drugs.
About this Structure
1JD2 is a Protein complex structure of sequences from Saccharomyces cerevisiae with and as ligands. Active as Proteasome endopeptidase complex, with EC number 3.4.25.1 Full crystallographic information is available from OCA.
Reference
Crystal structure of the 20 S proteasome:TMC-95A complex: a non-covalent proteasome inhibitor., Groll M, Koguchi Y, Huber R, Kohno J, J Mol Biol. 2001 Aug 17;311(3):543-8. PMID:11493007
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