1JD2

Crystal Structure of the yeast 20S Proteasome:TMC-95A complex: A non-covalent Proteasome Inhibitor

1JD2 の概要

• エントリーDOI: 10.2210/pdb1jd2/pdb
• 関連するPDBエントリー: 1G0U 1RYP
• 関連するBIRD辞書のPRD_ID: PRD_001096
• 分子名称: PROTEASOME COMPONENT Y7, PROTEASOME COMPONENT C11, PROTEASOME COMPONENT PRE2, ... (17 entities in total)
• 機能のキーワード: beta-sandwich, proteasome:inhibitor complex, hydrolase, hydrolase-hydrolase inhibitor complex, hydrolase/hydrolase inhibitor
• 由来する生物種: Saccharomyces cerevisiae (baker's yeast); 詳細
• 細胞内の位置: Cytoplasm: P23639 P22141 P30656 P23724 P30657 P38624 P23638 P40303 P32379 P40302 P21242 P21243 P25043 P25451
• タンパク質・核酸の鎖数: 30
• 化学式量合計: 705810.70

構造登録者

Groll, M.,Koguchi, Y.,Huber, R.,Kohno, J. (登録日: 2001-06-12, 公開日: 2002-02-13, 最終更新日: 2017-10-04)

主引用文献

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

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: 11493007
DOI: 10.1006/jmbi.2001.4869

実験手法

X-RAY DIFFRACTION (3 Å)