3BDM

yeast 20S proteasome:glidobactin A-complex

3BDM の概要

• エントリーDOI: 10.2210/pdb3bdm/pdb
• 関連するPDBエントリー: 1IRU 1PMA 1RYP 2ZCY
• 分子名称: Proteasome component Y7, Proteasome component C11, Proteasome component PRE2, ... (16 entities in total)
• 機能のキーワード: proteasome, ubiquitin, proteolysis, pathogen, virulence factor, cytoplasm, hydrolase, nucleus, protease, threonine protease, ubl conjugation, phosphoprotein, zymogen
• 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: 28
• 化学式量合計: 741454.12

構造登録者

Groll, M.,Dudler, R.,Kaiser, M. (登録日: 2007-11-15, 公開日: 2008-04-08, 最終更新日: 2023-11-01)

主引用文献

Groll, M.,Schellenberg, B.,Bachmann, A.S.,Archer, C.R.,Huber, R.,Powell, T.K.,Lindow, S.,Kaiser, M.,Dudler, R.
A plant pathogen virulence factor inhibits the eukaryotic proteasome by a novel mechanism
Nature, 452:755-758, 2008

PubMed Abstract: Pathogenic bacteria often use effector molecules to increase virulence. In most cases, the mode of action of effectors remains unknown. Strains of Pseudomonas syringae pv. syringae (Pss) secrete syringolin A (SylA), a product of a mixed non-ribosomal peptide/polyketide synthetase, in planta. Here we identify SylA as a virulence factor because a SylA-negative mutant in Pss strain B728a obtained by gene disruption was markedly less virulent on its host, Phaseolus vulgaris (bean). We show that SylA irreversibly inhibits all three catalytic activities of eukaryotic proteasomes, thus adding proteasome inhibition to the repertoire of modes of action of virulence factors. The crystal structure of the yeast proteasome in complex with SylA revealed a novel mechanism of covalent binding to the catalytic subunits. Thus, SylA defines a new class of proteasome inhibitors that includes glidobactin A (GlbA), a structurally related compound from an unknown species of the order Burkholderiales, for which we demonstrate a similar proteasome inhibition mechanism. As proteasome inhibitors are a promising class of anti-tumour agents, the discovery of a novel family of inhibitory natural products, which we refer to as syrbactins, may also have implications for the development of anti-cancer drugs. Homologues of SylA and GlbA synthetase genes are found in some other pathogenic bacteria, including the human pathogen Burkholderia pseudomallei, the causative agent of melioidosis. It is thus possible that these bacteria are capable of producing proteasome inhibitors of the syrbactin class.

PubMed: 18401409
DOI: 10.1038/nature06782

実験手法

X-RAY DIFFRACTION (2.7 Å)