1JD2
Crystal Structure of the yeast 20S Proteasome:TMC-95A complex: A non-covalent Proteasome Inhibitor
Summary for 1JD2
| Entry DOI | 10.2210/pdb1jd2/pdb |
| Related | 1G0U 1RYP |
| Related PRD ID | PRD_001096 |
| Descriptor | PROTEASOME COMPONENT Y7, PROTEASOME COMPONENT C11, PROTEASOME COMPONENT PRE2, ... (17 entities in total) |
| Functional Keywords | beta-sandwich, proteasome:inhibitor complex, hydrolase, hydrolase-hydrolase inhibitor complex, hydrolase/hydrolase inhibitor |
| Biological source | Saccharomyces cerevisiae (baker's yeast) More |
| Cellular location | Cytoplasm: P23639 P22141 P30656 P23724 P30657 P38624 P23638 P40303 P32379 P40302 P21242 P21243 P25043 P25451 |
| Total number of polymer chains | 30 |
| Total formula weight | 705810.70 |
| Authors | Groll, M.,Koguchi, Y.,Huber, R.,Kohno, J. (deposition date: 2001-06-12, release date: 2002-02-13, Last modification date: 2017-10-04) |
| Primary citation | Groll, M.,Koguchi, Y.,Huber, R.,Kohno, J. Crystal structure of the 20 S proteasome:TMC-95A complex: a non-covalent proteasome inhibitor. J.Mol.Biol., 311:543-548, 2001 Cited by PubMed Abstract: 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. PubMed: 11493007DOI: 10.1006/jmbi.2001.4869 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (3 Å) |
Structure validation
Download full validation report
