Insights from Modeling the 3D Structure of New Delhi Metallo-β-Lactamse and Its Binding Interactions with Antibiotic Drugs

Wang, Jing‐Fang; Chou, Kuo‐Chen

doi:10.1371/journal.pone.0018414

Cited by 60 publications

(43 citation statements)

References 58 publications

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“…The Met154Leu substitution was responsible for this high carbapenemase activity. This amino acid substitution was not located in what has been identified as the active site of NDM-1 or the amino acid residue that binds to the zinc ions (21,24). This is the second example of identification of amino acid substitution as a source of extended catalytic activity in an MBL structure.…”

mentioning

confidence: 87%

“…In addition, NDM-2-producing A. baumannii isolates have been reported from Egypt and Israel (7,10). NDM-2 differs from NDM-1 by a single amino acid substitution (Pro28Ala) located in the leader peptide of the enzyme that does not modify its hydrolytic properties compared to those of NDM-1 (7,21). We report here the identification of a novel NDM variant that possesses extended hydrolytic properties.…”

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confidence: 93%

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NDM-4 Metallo-β-Lactamase with Increased Carbapenemase Activity from Escherichia coli

Nordmann

Boulanger

Poirel

2012

Antimicrob Agents Chemother

137

118

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A clinical Escherichia coli isolate resistant to all ␤-lactams, including carbapenems, expressed a novel metallo-␤-lactamase (MBL), NDM-4, differing from NDM-1 by a single amino acid substitution (Met154Leu). NDM-4 possessed increased hydrolytic activity toward carbapenems and several cephalosporins compared to that of NDM-1. This amino acid substitution was not located in the known active sites of NDM-1, indicating that remote amino acid substitutions might also play a role in the extended activity of this MBL.A cquired metallo-␤-lactamases (MBLs) are emerging resistance determinants in clinically relevant Gram-negative species (19). NDM-1 (New Delhi metallo-␤-lactamase 1) has been recently identified, being first described from Klebsiella pneumoniae and Escherichia coli isolated in Sweden in 2008 from an Indian patient (23). NDM-1, as is the case for any MBL, confers a broad-spectrum ␤-lactam resistance, hydrolyzing penicillins, cephalosporins, and carbapenems but sparing monobactams (23). The rapid and large dissemination of NDM-1-producing Gram-negative species has been emphasized in many reports that have been published in the last 2 years (13,16,20). In Enterobacteriaceae, the bla NDM-1 gene has been shown to be carried by different plasmid types (IncA/C, IncF, IncL/M, or untypeable) (13,16,17). Most bla NDM-1 -encoding plasmids coharbored multiple and variable resistance determinants, including those for ␤-lactams, quinolones, aminoglycosides, rifampin, chloramphenicol, and macrolides (13,16,17). The bla NDM-1 gene has been widely identified in Enterobacteriaceae but also in Acinetobacter baumannii from Germany, India, the United Kingdom, and China (4, 5, 10, 11). In addition, NDM-2-producing A. baumannii isolates have been reported from Egypt and Israel (7, 10). NDM-2 differs from NDM-1 by a single amino acid substitution (Pro28Ala) located in the leader peptide of the enzyme that does not modify its hydrolytic properties compared to those of NDM-1 (7, 21). We report here the identification of a novel NDM variant that possesses extended hydrolytic properties.E. coli I5 was recovered from a urinary culture of a patient hospitalized in India in January 2010. Susceptibility testing was performed by disk diffusion assay (Sanofi-Diagnostic Pasteur, Marnes-la-Coquette, France) as previously described (6a). Results were interpreted according to the CLSI guidelines (6a). The MICs were determined by Etest (AB bioMérieux, Solna, Sweden) on Mueller-Hinton agar plates at 37°C. E. coli I5 was resistant to all ␤-lactams, including imipenem, meropenem, and ertapenem (Table 1). This isolate was additionally resistant to all tested aminoglycosides and fluoroquinolones. Production of MBL was assessed using Etest MBL (AB bioMérieux, Solna Sweden), which gave a positive result. Whole-cell DNA of E. coli isolate I5 was extracted using a QiaAmp minikit according to manufacturer recommendations (Qiagen, Courtaboeuf, France), and DNA was used as a template for the detection of different ␤-lactamases and 16S rRNA methylase genes...

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mentioning

confidence: 87%

mentioning

confidence: 93%

NDM-4 Metallo-β-Lactamase with Increased Carbapenemase Activity from Escherichia coli

Nordmann

Boulanger

Poirel

2012

Antimicrob Agents Chemother

137

118

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“…Such a criterion was originally used to define the binding pocket of ATP in the Cdk5-Nck5a* complex [61] that has later proved quite useful in identifying functional domains and stimulating the relevant truncation experiments [62]. The similar approach has also been used to define the binding pockets of many other receptor-ligand interactions important for drug design [63][64][65][66][67][68][69][70][71][72][73][74].…”

Section: Docking Of the Inhibitorsmentioning

confidence: 99%

Molecular Recognition of Human Angiotensin-Coverting Enzyme I (hACE I) and Different Inhibitors

Chu¹,

Min²,

Zhang³

et al. 2013

CTMC

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Abstract:The human angiontensin-converting enzyme I (hACEI) is a zinc metalloproteinase that hydrolytically cleaves a C-terminal dipeptide from a wide range of peptide substrates, and it plays an important role in regulating blood pressure. MD simulations and interaction energy calculations for docking and crystal structures were performed to investigate the correct conformation of the ACE with enalaprilat and nanopepetide. The analysis of root-mean-squrared fluctuation (RMSF), which is usually applied to measure the mobility and flexibility of the proteins, and dynamic correlation of residues show that the fluctuation pattern of the each two structure of the same ligand is almost the same mode. Hydrogen bond analysis shows that the correct crystal conformation is more stable than a wrong docking conformation. In addition, we are demonstrating that calculating interaction energy between protein and its ligands is an accurate and efficient way to select the correct conformation from docking conformations.

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“…Hence, bacterial resistance to β-lactam antibiotics can be achieved by 3 broad ways (Figure 3): 1) degrading or modifying the antibiotic before it can reach the site of action by production of enzymes from β-lactamase family; 2) modifying antibiotic target site with β-lactam resistant cell wall transpeptidase (this is major cause of resistance in several pathogens including Gram-positive Staphylococcal and Streptopcoccal species); 3) preventing the access of the antibiotic to the target by way of altered permeability or forced efflux (for example, MexA, BOprM antibiotic efflux pump, which is a major cause of resistance in Pseudomonas and in other pathogenic Gram-negative species) [18]. Out of these, the most common mechanism of bacterial resistance is the production of β-lacatamase enymes that hydrolyze the β-lactam antibiotics by cleaving the amide bond of β-lactam ring in an acylation-deacylation-based process [21,22]. First indentified in an isolate of Escherichia coli in 1940 [23] these enzymes are mainly found in Enterobacteriaceae family [24].…”

Section: β-Lactamase Enzymementioning

confidence: 99%

Insights on the structural characteristics of NDM-1: The journey so far

Saini¹,

Bansal²

2012

ABC

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New Delhi metallo-β-lactamase (NDM-1) has created a medical storm ever since it was first reported; as it is active on virtually all clinically used β-lactam antibiotics. NDM-1 rampancy worldwide is now considered a nightmare scenario, particularly due to its rapid dissemination. An underlying theme in the majority of recent studies is structural characterization as knowledge of the three-dimensional structure of NDM-1 shall help find connections between its structure and function. Moreover, structural details are even critical in order to reveal the resistance mechanism to β-lactam antibiotics. In this perspective, we review structural characteristics of NDM-1 that have been delineated since its first report. We anticipate that these structure-function connections made by its characterization shall further serve as future guidelines for elucidating pathways towards de novo design of functional inhibitors.

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Insights from Modeling the 3D Structure of New Delhi Metallo-β-Lactamse and Its Binding Interactions with Antibiotic Drugs

Cited by 60 publications

References 58 publications

NDM-4 Metallo-β-Lactamase with Increased Carbapenemase Activity from Escherichia coli

NDM-4 Metallo-β-Lactamase with Increased Carbapenemase Activity from Escherichia coli

Molecular Recognition of Human Angiotensin-Coverting Enzyme I (hACE I) and Different Inhibitors

Insights on the structural characteristics of NDM-1: The journey so far

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