Biochemical and structural characterization of the subclass B1 metallo-beta-lactamase VIM-4

Patricia Lassaux, Daouda A K Traore, Elodie Loisel, Jean -Denis Docquier, Jean Sebasiten Sohier, Clementine Laurent, Carine Bebrone, Jean -Marie Frere, Jean -Luc Ferrer, Moreno Galleni

Research output: Contribution to journalArticleResearchpeer-review

Abstract

The metallo-beta-lactamase VIM-4, mainly found in Pseudomonas aeruginosa or Acinetobacter baumannii, was produced in Escherichia coli and characterized by biochemical and X-ray techniques. A detailed kinetic study performed in the presence of Zn2+ at concentrations ranging from 0.4 to 100 uM showed that VIM-4 exhibits a kinetic profile similar to the profiles of VIM-2 and VIM-1. However, VIM-4 is more active than VIM-1 against benzylpenicillin, cephalothin, nitrocefin, and imipenem and is less active than VIM-2 against ampicillin and meropenem. The crystal structure of the dizinc form of VIM-4 was solved at 1.9 ??. The sole difference between VIM-4 and VIM-1 is found at residue 228, which is Ser in VIM-1 and Arg in VIM-4. This substitution has a major impact on the VIM-4 catalytic efficiency compared to that of VIM-1. In contrast, the differences between VIM-2 and VIM-4 seem to be due to a different position of the flapping loop and two substitutions in loop 2. Study of the thermal stability and the activity of the holo- and apo-VIM-4 enzymes revealed that Zn2+ ions have a pronounced stabilizing effect on the enzyme and are necessary for preserving the structure.
Original languageEnglish
Pages (from-to)1248 - 1255
Number of pages8
JournalAntimicrobial Agents and Chemotherapy
Volume55
Issue number3
DOIs
Publication statusPublished - 2011
Externally publishedYes

Cite this

Lassaux, Patricia ; Traore, Daouda A K ; Loisel, Elodie ; Docquier, Jean -Denis ; Sohier, Jean Sebasiten ; Laurent, Clementine ; Bebrone, Carine ; Frere, Jean -Marie ; Ferrer, Jean -Luc ; Galleni, Moreno. / Biochemical and structural characterization of the subclass B1 metallo-beta-lactamase VIM-4. In: Antimicrobial Agents and Chemotherapy. 2011 ; Vol. 55, No. 3. pp. 1248 - 1255.
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title = "Biochemical and structural characterization of the subclass B1 metallo-beta-lactamase VIM-4",
abstract = "The metallo-beta-lactamase VIM-4, mainly found in Pseudomonas aeruginosa or Acinetobacter baumannii, was produced in Escherichia coli and characterized by biochemical and X-ray techniques. A detailed kinetic study performed in the presence of Zn2+ at concentrations ranging from 0.4 to 100 uM showed that VIM-4 exhibits a kinetic profile similar to the profiles of VIM-2 and VIM-1. However, VIM-4 is more active than VIM-1 against benzylpenicillin, cephalothin, nitrocefin, and imipenem and is less active than VIM-2 against ampicillin and meropenem. The crystal structure of the dizinc form of VIM-4 was solved at 1.9 ??. The sole difference between VIM-4 and VIM-1 is found at residue 228, which is Ser in VIM-1 and Arg in VIM-4. This substitution has a major impact on the VIM-4 catalytic efficiency compared to that of VIM-1. In contrast, the differences between VIM-2 and VIM-4 seem to be due to a different position of the flapping loop and two substitutions in loop 2. Study of the thermal stability and the activity of the holo- and apo-VIM-4 enzymes revealed that Zn2+ ions have a pronounced stabilizing effect on the enzyme and are necessary for preserving the structure.",
author = "Patricia Lassaux and Traore, {Daouda A K} and Elodie Loisel and Docquier, {Jean -Denis} and Sohier, {Jean Sebasiten} and Clementine Laurent and Carine Bebrone and Frere, {Jean -Marie} and Ferrer, {Jean -Luc} and Moreno Galleni",
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doi = "10.1128/AAC.01486-09",
language = "English",
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pages = "1248 -- 1255",
journal = "Antimicrobial Agents and Chemotherapy",
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Lassaux, P, Traore, DAK, Loisel, E, Docquier, J-D, Sohier, JS, Laurent, C, Bebrone, C, Frere, J-M, Ferrer, J-L & Galleni, M 2011, 'Biochemical and structural characterization of the subclass B1 metallo-beta-lactamase VIM-4' Antimicrobial Agents and Chemotherapy, vol. 55, no. 3, pp. 1248 - 1255. https://doi.org/10.1128/AAC.01486-09

Biochemical and structural characterization of the subclass B1 metallo-beta-lactamase VIM-4. / Lassaux, Patricia; Traore, Daouda A K; Loisel, Elodie; Docquier, Jean -Denis; Sohier, Jean Sebasiten; Laurent, Clementine; Bebrone, Carine; Frere, Jean -Marie; Ferrer, Jean -Luc; Galleni, Moreno.

In: Antimicrobial Agents and Chemotherapy, Vol. 55, No. 3, 2011, p. 1248 - 1255.

Research output: Contribution to journalArticleResearchpeer-review

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T1 - Biochemical and structural characterization of the subclass B1 metallo-beta-lactamase VIM-4

AU - Lassaux, Patricia

AU - Traore, Daouda A K

AU - Loisel, Elodie

AU - Docquier, Jean -Denis

AU - Sohier, Jean Sebasiten

AU - Laurent, Clementine

AU - Bebrone, Carine

AU - Frere, Jean -Marie

AU - Ferrer, Jean -Luc

AU - Galleni, Moreno

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N2 - The metallo-beta-lactamase VIM-4, mainly found in Pseudomonas aeruginosa or Acinetobacter baumannii, was produced in Escherichia coli and characterized by biochemical and X-ray techniques. A detailed kinetic study performed in the presence of Zn2+ at concentrations ranging from 0.4 to 100 uM showed that VIM-4 exhibits a kinetic profile similar to the profiles of VIM-2 and VIM-1. However, VIM-4 is more active than VIM-1 against benzylpenicillin, cephalothin, nitrocefin, and imipenem and is less active than VIM-2 against ampicillin and meropenem. The crystal structure of the dizinc form of VIM-4 was solved at 1.9 ??. The sole difference between VIM-4 and VIM-1 is found at residue 228, which is Ser in VIM-1 and Arg in VIM-4. This substitution has a major impact on the VIM-4 catalytic efficiency compared to that of VIM-1. In contrast, the differences between VIM-2 and VIM-4 seem to be due to a different position of the flapping loop and two substitutions in loop 2. Study of the thermal stability and the activity of the holo- and apo-VIM-4 enzymes revealed that Zn2+ ions have a pronounced stabilizing effect on the enzyme and are necessary for preserving the structure.

AB - The metallo-beta-lactamase VIM-4, mainly found in Pseudomonas aeruginosa or Acinetobacter baumannii, was produced in Escherichia coli and characterized by biochemical and X-ray techniques. A detailed kinetic study performed in the presence of Zn2+ at concentrations ranging from 0.4 to 100 uM showed that VIM-4 exhibits a kinetic profile similar to the profiles of VIM-2 and VIM-1. However, VIM-4 is more active than VIM-1 against benzylpenicillin, cephalothin, nitrocefin, and imipenem and is less active than VIM-2 against ampicillin and meropenem. The crystal structure of the dizinc form of VIM-4 was solved at 1.9 ??. The sole difference between VIM-4 and VIM-1 is found at residue 228, which is Ser in VIM-1 and Arg in VIM-4. This substitution has a major impact on the VIM-4 catalytic efficiency compared to that of VIM-1. In contrast, the differences between VIM-2 and VIM-4 seem to be due to a different position of the flapping loop and two substitutions in loop 2. Study of the thermal stability and the activity of the holo- and apo-VIM-4 enzymes revealed that Zn2+ ions have a pronounced stabilizing effect on the enzyme and are necessary for preserving the structure.

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DO - 10.1128/AAC.01486-09

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