5MXR

Crystal Structure of the Acquired VIM-2 Metallo-beta-Lactamase in Complex with ANT-330 Inhibitor

Summary for 5MXR

• Entry DOI: 10.2210/pdb5mxr/pdb
• Descriptor: Beta-lactamase VIM-2, ZINC ION, ACETATE ION, ... (5 entities in total)
• Functional Keywords: metallo-beta-lactamase fold, zinc-dependent hydrolase, pfam00753, alpha-beta-beta-alpha sandwich, hydrolase
• Biological source: Pseudomonas aeruginosa
• Total number of polymer chains: 1
• Total formula weight: 25590.41

Authors

Docquier, J.D.,De Luca, F.,Benvenuti, M.,Di Pisa, F.,Pozzi, C.,Mangani, S. (deposition date: 2017-01-24, release date: 2018-03-14, Last modification date: 2024-05-08)

Primary citation

Leiris, S.,Coelho, A.,Castandet, J.,Bayet, M.,Lozano, C.,Bougnon, J.,Bousquet, J.,Everett, M.,Lemonnier, M.,Sprynski, N.,Zalacain, M.,Pallin, T.D.,Cramp, M.C.,Jennings, N.,Raphy, G.,Jones, M.W.,Pattipati, R.,Shankar, B.,Sivasubrahmanyam, R.,Soodhagani, A.K.,Juventhala, R.R.,Pottabathini, N.,Pothukanuri, S.,Benvenuti, M.,Pozzi, C.,Mangani, S.,De Luca, F.,Cerboni, G.,Docquier, J.D.,Davies, D.T.
SAR Studies Leading to the Identification of a Novel Series of Metallo-beta-lactamase Inhibitors for the Treatment of Carbapenem-Resistant Enterobacteriaceae Infections That Display Efficacy in an Animal Infection Model.
Acs Infect Dis., 5:131-140, 2019

PubMed 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.

PubMed: 30427656
DOI: 10.1021/acsinfecdis.8b00246

Experimental method

X-RAY DIFFRACTION (1.75 Å)