Structure of the extended-spectrum β-lactamase TEM-72 inhibited by citrate.

@article{Docquier2011StructureOT,
  title={Structure of the extended-spectrum $\beta$-lactamase TEM-72 inhibited by citrate.},
  author={J. Docquier and M. Benvenuti and V. Calderone and G. Rossolini and S. Mangani},
  journal={Acta crystallographica. Section F, Structural biology and crystallization communications},
  year={2011},
  volume={67 Pt 3},
  pages={
          303-6
        }
}
  • J. Docquier, M. Benvenuti, +2 authors S. Mangani
  • Published 2011
  • Biology, Medicine
  • Acta crystallographica. Section F, Structural biology and crystallization communications
TEM-72, a class A β-lactamase identified in isolates of Enterobacteriaceae, is a quadruple mutant of TEM-1 (Q39K, M182T, G238S and E240K) and shows extended-spectrum β-lactamase (ESBL) properties arising from the G238S and E240K substitutions. Although many structures of TEM variants have been published, they do not include an enzyme with the simultaneous presence of both of the ESBL-conferring G238S and E240K substitutions. Furthermore, the structure shows the presence of a citrate anion bound… Expand

Figures, Tables, and Topics from this paper

The study of the role of mutations M182T and Q39K in the TEM-72 β-lactamase structure by the molecular dynamics method
TLDR
The role of associated mutations in structure of β-lactamase TEM-72, which contains two key mutations (G238S, E240K) and two associated mutations (Q39K, M182T) is investigated by means of molecular dynamics simulation and it appears that the latter mutation promoted optimization of the conformational mobility ofβ-l lactamase and may influence the enzyme activity. Expand
[Investigation the role of mutations M182T and Q39K in structure of beta-lactamase TEM-72 by molecular dynamics method].
TLDR
This work has investigated the role of associated mutations in structure of b-lactamase TEM-72, which contain two key mutation (G238S, E240K) and two associated mutations (Q39K, M182T) by means of simulation of molecular dynamics, and it seems that the last mutation serves for optimization of conformational mobility ofb-lacticamase and may influence on enzyme activity. Expand
Structural and Mechanistic Basis for Extended-Spectrum Drug-Resistance Mutations in Altering the Specificity of TEM, CTX-M, and KPC β-lactamases
TLDR
The structural and mechanistic basis for the expanded substrate specificity of each TEM, CTX-M, and KPC enzymes that result from natural mutations that confer oxyimino-cephalosporin resistance are discussed. Expand
Structural basis for the extended substrate spectrum of AmpC BER and structure-guided discovery of the inhibition activity of citrate against the class C β-lactamases AmpC BER and CMY-10.
  • J. Na, S. Cha
  • Chemistry, Medicine
  • Acta crystallographica. Section D, Structural biology
  • 2016
TLDR
It is demonstrated that citrate, a primary metabolite that is widely used as a food additive, is a competitive inhibitor of two class C β-lactamases (AmpC BER and CMY-10) and suggested that the citrate scaffold is recognized by the active sites of class Cβ-l lactamases. Expand
The impact of long-distance mutations on the Ω-loop conformation in TEM type β-lactamases
TLDR
Residue Interaction Networks were constructed from molecular dynamic trajectories of β-lactamase TEM-1 and its variants with two key substitutions, G238S and E240K, and their combinations with secondary ones (M182T and Q39K) and it was shown that key mutations weakened the stability of contact inside the Ω-loop thus increasing its mobility. Expand
Crystal Structure of the Pseudomonas aeruginosa BEL-1 Extended-Spectrum β-Lactamase and Its Complexes with Moxalactam and Imipenem
TLDR
A BEL-1 variant showing the single Leu162Phe substitution (BEL-2) confers a higher level of resistance to CAZ, CTX, and FEP and shows significantly lower Km values thanbel-1, especially with oxyiminocephalosporins. Expand
Molecular dynamics of class A β-lactamases-effects of substrate binding.
TLDR
Agreement between NMR relaxation parameters and theoretical results highlights the dynamic duality of class A β-lactamases: enzymes that are highly structured on the ps-ns timescale, with important flexibility on the μs-ms timescale in regions such as the Ω loop. Expand
Impact of Residue R65 on the Stabilization of TEM-Type β-Lactamases with Substitution of M182T
For the experimental study of the role of the R65 residue in the stabilization of β-lactamases with the substitution of M182T, predicted by the analysis of the residue interaction networks (RINs),Expand
Mutual influence of secondary and key drug‐resistance mutations on catalytic properties and thermal stability of TEM‐type β‐lactamases
TLDR
Replacement of Q39 by lysine in combination with the key drug resistance mutations may be responsible for loss of protein thermal stability and elevated mobility of its secondary structure elements. Expand
Atomic‐Resolution Structure of a Class C β‐Lactamase and Its Complex with Avibactam
TLDR
A comparison of the native and avibactam‐bound structures revealed new details in the conformations of residues relevant for substrate and/or inhibitor binding, and two inhibitor conformations that were likely to correspond to two different states occurring during inhibitor carbamylation/recyclization. Expand
...
1
2
...

References

SHOWING 1-10 OF 33 REFERENCES
TEM-72, a New Extended-Spectrum β-Lactamase Detected in Proteus mirabilis and Morganella morganii in Italy
TLDR
Kinetic analysis showed that TEM-72 exhibits an extended-spectrum activity, including activity against oxyimino-cephalosporins and aztreonam, and Expression ofblaT EM-72 in Escherichia coli was capable of decreasing the host susceptibility to the above drugs. Expand
Crystal Structure of the Narrow-Spectrum OXA-46 Class D β-Lactamase: Relationship between Active-Site Lysine Carbamylation and Inhibition by Polycarboxylates
TLDR
The three-dimensional structure of OXA-46 is obtained, which shows the overall fold of active serine β-lactamases and a dimeric quaternary structure, and interestingly, the three subunits present in the asymmetric unit showed some structural heterogeneity, only one of which presented a carbamylated lysine recognized as an important functional feature of class D enzymes. Expand
Structural consequences of the inhibitor-resistant Ser130Gly substitution in TEM beta-lactamase.
TLDR
The conservation of similar accommodations among IRT mutants suggests that resistance arises from common mechanisms, despite the disparate locations of the various substitutions. Expand
β-Lactamase inhibitors: evolving compounds for evolving resistance targets
TLDR
The many and diverse β-lactamases produced by bacteria, particularly by Gram-negative pathogens, are increasingly posing a serious threat to the clinical utility of β- lactams, and research toward universal inhibitors is spurred towards universal inhibitors. Expand
The Structural Bases of Antibiotic Resistance in the Clinically Derived Mutant β-Lactamases TEM-30, TEM-32, and TEM-34*
TLDR
In these three IRT structures, distant substitutions result in accommodations that converge on the same point of action, the local environment of Ser-130, the most pernicious mutants of β-lactamases. Expand
Updated Functional Classification of β-Lactamases
TLDR
The functional classification scheme updated herein is based on the 1995 proposal and includes group 1 (class C) cephalosporinases; group 2 (classes A and D) broad-spectrum, inhibitor-resistant, and extended-spectrums β-lactamases and serine carbapenemases; and group 3 metallo-β-lacticamases. Expand
Structure of the wild-type TEM-1 beta-lactamase at 1.55 A and the mutant enzyme Ser70Ala at 2.1 A suggest the mode of noncovalent catalysis for the mutant enzyme.
TLDR
The structure of the mutant enzyme suggests that this water molecule can assume the role of an active-site nucleophile and carry out noncovalent catalysis, suggesting common chemical principles in the utilization of nucleophilic serine in the active site of different enzymes. Expand
Crystal structure of an acylation transition-state analog of the TEM-1 beta-lactamase. Mechanistic implications for class A beta-lactamases.
TLDR
The crystal structure of a phosphonate complex of the class A TEM-1 beta-lactamase has been determined and lead to a self-consistent proposal for a mechanism of catalysis by these enzymes. Expand
Inhibition of TEM-2 beta-lactamase from Escherichia coli by clavulanic acid: observation of intermediates by electrospray ionization mass spectrometry.
TLDR
A mechanistic scheme for the reaction of clavulanate with TEM-2 beta-lactamase is proposed in which acylation at Ser-70 and subsequent decarboxylation is followed either by cross-linking with Ser-130 to form a vinyl ether or by reformation of unmodified enzyme via a Ser- 70 linked (hydrated) aldehyde. Expand
Genetic and Structural Insights into the Dissemination Potential of the Extremely Broad-Spectrum Class A β-Lactamase KPC-2 Identified in an Escherichia coli Strain and an Enterobacter cloacae Strain Isolated from the Same Patient in France
TLDR
Structure analysis and docking simulations with cefotaxime and imipenem provided further insights into the molecular basis of the extremely broad spectrum of KPC-2, which behaves as a cefOTaximase with significant activity against carbapenems. Expand
...
1
2
3
4
...