PDBsum entry 5ovt

Hydrolase

PDB id: 5ovt

Contents

Protein chains

(+ 1 more) 183 a.a.

Ligands

ACE-IML-ILE-THR-6VO ×7

PO4 ×7

Waters ×79

PDB id:

5ovt

Name:

Hydrolase

Title:

Thiobacillus denitrificans bph in complex with epoxomicin

Structure:

Bph. Chain: a, b, c, d, e, f, g. Engineered: yes. Epoxomicin. Chain: a, b, c, d, e, f, g. Engineered: yes. Other_details: covalent proteasome inhibitor

Source:

Thiobacillus denitrificans. Organism_taxid: 36861. Expressed in: escherichia coli. Expression_system_taxid: 562. Synthetic: yes. Synthetic construct. Organism_taxid: 32630

Resolution:

2.95Å R-factor: 0.173 R-free: 0.189

Authors:

A.C.D.Fuchs,R.Albrecht,J.Martin,M.D.Hartmann

Key ref:

A.C.D.Fuchs et al. (2018). 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. PubMed id: 29183996

Date:

29-Aug-17 Release date: 06-Dec-17

Protein chains

A0A2R2JFN0  (A0A2R2JFN0_THIDE) -  BPH from Thiobacillus denitrificans

Seq: 201 a.a.

Struc: 183 a.a.

J Biol Chem 293:920-930 (2018)

PubMed id: 29183996

Structural characterization of the bacterial proteasome homolog BPH reveals a tetradecameric double-ring complex with unique inner cavity properties.

A.C.D.Fuchs, L.Maldoner, K.Hipp, M.D.Hartmann, J.Martin.

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 theThiobacillus denitrificansandCupriavidus metalliduransBPHs 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.