1jd2
From Proteopedia
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| , resolution 3.0Å | |||||||
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| Ligands: | , | ||||||
| Activity: | Proteasome endopeptidase complex, with EC number 3.4.25.1 | ||||||
| Related: | 1RYP, 1G0U
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| Resources: | FirstGlance, OCA, PDBsum, RCSB | ||||||
| Coordinates: | save as pdb, mmCIF, xml | ||||||
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. 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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