5OVT

Thiobacillus denitrificans BPH in complex with Epoxomicin

5OVT の概要

• エントリーDOI: 10.2210/pdb5ovt/pdb
• 分子名称: BPH, Epoxomicin, PHOSPHATE ION, ... (4 entities in total)
• 機能のキーワード: protein degradation, beta-proteobacteria proteasome homologue, hydrolase, covalent proteasome inhibitor
• 由来する生物種: Thiobacillus denitrificans; 詳細
• タンパク質・核酸の鎖数: 14
• 化学式量合計: 158919.57

構造登録者

Fuchs, A.C.D.,Albrecht, R.,Martin, J.,Hartmann, M.D. (登録日: 2017-08-29, 公開日: 2017-12-06, 最終更新日: 2024-10-23)

主引用文献

Fuchs, A.C.D.,Maldoner, L.,Hipp, K.,Hartmann, M.D.,Martin, J.
Structural characterization of the bacterial proteasome homolog BPH reveals a tetradecameric double-ring complex with unique inner cavity properties.
J. Biol. Chem., 293:920-930, 2018

PubMed Abstract: Eukaryotic and archaeal proteasomes are paradigms for self-compartmentalizing proteases. To a large extent, their function requires interplay with hexameric ATPases associated with diverse cellular activities (AAA+) that act as substrate unfoldases. Bacteria have various types of self-compartmentalizing proteases; in addition to the proteasome itself, these include the proteasome homolog HslV, which functions together with the AAA+ HslU; the ClpP protease with its partner AAA+ ClpX; and Anbu, a recently characterized ancestral proteasome variant. Previous bioinformatic analysis has revealed a novel bacterial member of the proteasome family Betaproteobacteria proteasome homolog (BPH). Using cluster analysis, we here affirmed that BPH evolutionarily descends from HslV. Crystal structures of the and BPHs disclosed a homo-oligomeric double-ring architecture in which the active sites face the interior of the cylinder. Using small-angle X-ray scattering (SAXS) and electron microscopy averaging, we found that BPH forms tetradecamers in solution, unlike the dodecamers seen in HslV. Although the highly acidic inner surface of BPH was in striking contrast to the cavity characteristics of the proteasome and HslV, a classical proteasomal reaction mechanism could be inferred from the covalent binding of the proteasome-specific inhibitor epoxomicin to BPH. A ligand-bound structure implied that the elongated BPH inner pore loop may be involved in substrate recognition. The apparent lack of a partner unfoldase and other unique features, such as Ser replacing Thr as the catalytic residue in certain BPH subfamilies, suggest a proteolytic function for BPH distinct from those of known bacterial self-compartmentalizing proteases.

PubMed: 29183996
DOI: 10.1074/jbc.M117.815258

実験手法

X-RAY DIFFRACTION (2.95 Å)