7DTN

Crystal structure of metallo-beta-lactamase IMP-1 mutant (D120E) in complex with citrate.

Summary for 7DTN

• Entry DOI: 10.2210/pdb7dtn/pdb
• Descriptor: Metallo-beta-lactamase type 2, ZINC ION, CITRATE ANION, ... (5 entities in total)
• Functional Keywords: metallo-beta-lactamase, zinc(ii) ion, citrate, hydrolase
• Biological source: Serratia marcescens
• Total number of polymer chains: 4
• Total formula weight: 102651.16

Authors

Yamaguchi, Y.,Kurosaki, H. (deposition date: 2021-01-06, release date: 2021-08-04, Last modification date: 2023-11-29)

Primary citation

Yamaguchi, Y.,Kato, K.,Ichimaru, Y.,Jin, W.,Sakai, M.,Abe, M.,Wachino, J.I.,Arakawa, Y.,Miyagi, Y.,Imai, M.,Fukuishi, N.,Yamagata, Y.,Otsuka, M.,Fujita, M.,Kurosaki, H.
Crystal Structures of Metallo-beta-Lactamase (IMP-1) and Its D120E Mutant in Complexes with Citrate and the Inhibitory Effect of the Benzyl Group in Citrate Monobenzyl Ester.
J.Med.Chem., 64:10019-10026, 2021

PubMed Abstract: The emergence and rapid spread of carbapenem-resistant pathogens producing metallo-β-lactamases such as IMP-1 and NDM-1 have been of great concern in the global clinical setting. The X-ray crystal structures of IMP-1 from and its single mutant, D120E, in complexes with citrate were determined at resolutions of 2.00 and 1.85 Å, respectively. Two crystal structures indicate that a single mutation at position 120 caused a structural change around Zn1, where the geometry changes from a tetrahedron in the native IMP-1 to a square pyramid in D120E. Based on these two complex structures, the authors synthesized citrate monobenzyl ester to evaluate the structural requirement for the inhibitory activity against IMP-1 and compared the inhibitory activities with nonsubstituted citrate. The introduction of a benzyl group into citrate enhanced the inhibitory activity in comparison to citrate (IC > 5 mM).

PubMed: 34242022
DOI: 10.1021/acs.jmedchem.1c00308

Experimental method

X-RAY DIFFRACTION (1.85 Å)