PDBsum entry 5mxr

Hydrolase

PDB id: 5mxr

Contents

Protein chain

232 a.a.

Ligands

ACT

JTY ×2

Metals

_ZN ×3

Waters ×120

PDB id:

5mxr

Name:

Hydrolase

Title:

Crystal structure of the acquired vim-2 metallo-beta-lactamase in complex with ant-330 inhibitor

Structure:

Beta-lactamase vim-2. Chain: a. Fragment: vim-2 mature protein. Synonym: class b beta-lactamase,class b carbapenemase vim-2,metallo beta lactamase vim-2,metallo beta-lactamase,metallo-beta-lactamase, metallo-beta-lactamase vim-2,metallo-beta-lactamase vim-2,vim-2 metallo-beta-lactamase,vim-2 protein. Engineered: yes

Source:

Pseudomonas aeruginosa. Organism_taxid: 287. Gene: blavim-2, bla vim-2, bla-vim-2, blasvim-2, blavim2, blm, vim- 2, vim-2, paerug_p32_london_17_vim_2_10_11_06255. Expressed in: escherichia coli. Expression_system_taxid: 469008.

Resolution:

1.75Å R-factor: 0.200 R-free: 0.242

Authors:

J.D.Docquier,F.De Luca,M.Benvenuti,F.Di Pisa,C.Pozzi,S.Mangani

Key ref:

S.Leiris et al. (2019). SAR Studies Leading to the Identification of a Novel Series of Metallo-β-lactamase Inhibitors for the Treatment of Carbapenem-Resistant Enterobacteriaceae Infections That Display Efficacy in an Animal Infection Model. ACS Infect Dis, 5, 131-140. PubMed id: 30427656 DOI: 10.1021/acsinfecdis.8b00246

Date:

24-Jan-17 Release date: 14-Mar-18

Protein chain

Q9K2N0  (Q9K2N0_PSEAI) -  Metallo-beta-lactamase type 2 from Pseudomonas aeruginosa

Seq: 266 a.a.

Struc: 232 a.a.

Enzyme reactions

• Enzyme class: E.C.3.5.2.6 - beta-lactamase.
• Pathway: Penicillin Biosynthesis and Metabolism
• Reaction: a beta-lactam + H2O = a substituted beta-amino acid
• Cofactor: Zn(2+)

DOI no: 10.1021/acsinfecdis.8b00246

ACS Infect Dis 5:131-140 (2019)

PubMed id: 30427656

SAR Studies Leading to the Identification of a Novel Series of Metallo-β-lactamase Inhibitors for the Treatment of Carbapenem-Resistant Enterobacteriaceae Infections That Display Efficacy in an Animal Infection Model.

S.Leiris, A.Coelho, J.Castandet, M.Bayet, C.Lozano, J.Bougnon, J.Bousquet, M.Everett, M.Lemonnier, N.Sprynski, M.Zalacain, T.D.Pallin, M.C.Cramp, N.Jennings, G.Raphy, M.W.Jones, R.Pattipati, B.Shankar, R.Sivasubrahmanyam, A.K.Soodhagani, R.R.Juventhala, N.Pottabathini, S.Pothukanuri, M.Benvenuti, C.Pozzi, S.Mangani, F.De Luca, G.Cerboni, J.D.Docquier, D.T.Davies.

ABSTRACT

The clinical effectiveness of carbapenem antibiotics such as meropenem is becoming increasingly compromised by the spread of both metallo-β-lactamase (MBL) and serine-β-lactamase (SBL) enzymes on mobile genetic elements, stimulating research to find new β-lactamase inhibitors to be used in conjunction with carbapenems and other β-lactam antibiotics. Herein, we describe our initial exploration of a novel chemical series of metallo-β-lactamase inhibitors, from concept to efficacy, in a survival model using an advanced tool compound (ANT431) in conjunction with meropenem.