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Literature summary for 3.5.2.6 extracted from

  • Kumar, G.; Issa, B.; Biswal, S.; Jain, D.; Bhattacharjee, A.; Ghosh, A.S.
    Glutamic acid at position 152 and serine at position 191 are the key residues required for the metallo-beta-lactamase activity of NDM-7 (2019), Int. J. Antimicrob. Agents, 55, 105824 .
    View publication on PubMed
Search for more literature for 3.5.2.6

Cloned(Commentary)

Cloned (Comment) Organism
gene blaNDM-7, recombinant expression of N-terminally His6-tagged wild-type and mutant enzymes in Escherichia coli strains BL21(DE3) and CS109, subcloning in Escherichia coli strain XL-1 Blue. Host Escherichia coli strain CS109 harbouring cloned blaNDM-7 displays a resistant status with over 60fold increased resistance compared to control strain CS109 for all penicillins, cephalosporin and carbapenems tested Klebsiella pneumoniae

Protein Variants

Protein Variants Comment Organism
D223A site-directed mutagenesis, the mutation does not signifcantly affect resistance of the cells against antibiotics Klebsiella pneumoniae
E152A site-directed mutagenesis, the mutant shows highly declined resistance to antibiotics compared to wild-type NDM-7 Klebsiella pneumoniae
E152A/S191A site-directed mutagenesis, the double mutant shows 2fold reduced antibiotic resistance compared to single mutants, but substantially declined resistance compared to wild-type NDM-7 Klebsiella pneumoniae
K216A site-directed mutagenesis, the mutation does not signifcantly affect resistance of the cells against antibiotics Klebsiella pneumoniae
S191A site-directed mutagenesis, mutant shows highly declined resistance to antibiotics compared to wild-type NDM-7 Klebsiella pneumoniae
S213A site-directed mutagenesis, the mutation does not signifcantly affect resistance of the cells against antibiotics Klebsiella pneumoniae

Metals/Ions

Metals/Ions Comment Organism Structure
Zn2+ the active-site residues His120, His122 and His189 are co-ordinated to Zn1 metal ion, whereas Asp124, Cys208 and His250 are co-ordinated to Zn2 metal ion for their catalytic activity. The di-zinc centre of NDM-7 is located at the bottom of the shallow groove and is a part of the binding pocket of the enzyme. The two Zn metal ions present in the active-site cleft take part in the catalytic activity of the NDM-7 via bridging to different active-site residues by forming strong interactions Klebsiella pneumoniae

Natural Substrates/ Products (Substrates)

Natural Substrates Organism Comment (Nat. Sub.) Natural Products Comment (Nat. Pro.) Rev. Reac.
amoxicillin + H2O Klebsiella pneumoniae
-
 (2R,4S)-2-[(R)-[[(2R)-2-amino-2-(4-hydroxyphenyl)acetyl]amino](carboxy)methyl]-5,5-dimethyl-1,3-thiazolidine-4-carboxylic acid
-
 ?
amoxicillin + H2O Klebsiella pneumoniae NDM-7
-
 (2R,4S)-2-[(R)-[[(2R)-2-amino-2-(4-hydroxyphenyl)acetyl]amino](carboxy)methyl]-5,5-dimethyl-1,3-thiazolidine-4-carboxylic acid
-
 ?
ampicilin + H2O Klebsiella pneumoniae
-
 (2R,4S)-2-[(R)-[[(2R)-2-amino-2-phenylacetyl]amino](carboxy)methyl]-5,5-dimethyl-1,3-thiazolidine-4-carboxylic acid
-
 ?
carbapenem + H2O Klebsiella pneumoniae
-
 [(2R)-2,3-dihydro-1H-pyrrol-2-yl]acetic acid
-
 ?
carbapenem + H2O Klebsiella pneumoniae NDM-7
-
 [(2R)-2,3-dihydro-1H-pyrrol-2-yl]acetic acid
-
 ?
cephalothin + H2O Klebsiella pneumoniae
-
 (2R)-5-[(acetyloxy)methyl]-2-[(R)-carboxy[2-(thiophen-2-yl)acetamido]methyl]-3,6-dihydro-2H-1,3-thiazine-4-carboxylic acid
-
 ?
doripenem + H2O Klebsiella pneumoniae
-
 (4R,5S)-5-[(1S,2R)-1-carboxy-2-hydroxypropyl]-4-methyl-3-(((3S,5S)-5-[(sulfamoylamino)methyl]pyrrolidin-3-yl)sulfanyl)-4,5-dihydro-1H-pyrrole-2-carboxylic acid
-
 ?
imipenem + H2O Klebsiella pneumoniae
-
 (5R)-3-[[2-(carbonoimidoylamino)ethyl]sulfanyl]-5-[(1S,2R)-1-carboxy-2-hydroxypropyl]-4,5-dihydro-1H-pyrrole-2-carboxylic acid
-
 ?
meropenem + H2O Klebsiella pneumoniae
-
 (4R,5S)-5-[(1S,2R)-1-carboxy-2-hydroxypropyl]-3-[[(3S,5S)-5-(dimethylcarbamoyl)pyrrolidin-3-yl]sulfanyl]-4-methyl-4,5-dihydro-1H-pyrrole-2-carboxylic acid
-
 ?
additional information Klebsiella pneumoniae resistance to antibiotics of recombinant His-tagged wild-type and mutant enzymes expressed in Escherichia coli strain CS109, overview ?
-
-
additional information Klebsiella pneumoniae NDM-7 resistance to antibiotics of recombinant His-tagged wild-type and mutant enzymes expressed in Escherichia coli strain CS109, overview ?
-
-
penicillin G + H2O Klebsiella pneumoniae
-
 (2R,4S)-2-[(R)-carboxy[(phenylacetyl)amino]methyl]-5,5-dimethyl-1,3-thiazolidine-4-carboxylic acid
-
 ?
penicillin G + H2O Klebsiella pneumoniae NDM-7
-
 (2R,4S)-2-[(R)-carboxy[(phenylacetyl)amino]methyl]-5,5-dimethyl-1,3-thiazolidine-4-carboxylic acid
-
 ?

Organism

Organism UniProt Comment Textmining
Klebsiella pneumoniae A0A173MZL7
-
-
Klebsiella pneumoniae NDM-7 A0A173MZL7
-
-

Purification (Commentary)

Purification (Comment) Organism
recombinant active N-terminally His6-tagged wild-type and mutant enzymes from Escherichia coli by nickel affinity chromatography to homogeneity Klebsiella pneumoniae

Substrates and Products (Substrate)

Substrates Comment Substrates Organism Products Comment (Products) Rev. Reac.
amoxicillin + H2O
-
 Klebsiella pneumoniae (2R,4S)-2-[(R)-[[(2R)-2-amino-2-(4-hydroxyphenyl)acetyl]amino](carboxy)methyl]-5,5-dimethyl-1,3-thiazolidine-4-carboxylic acid
-
 ?
amoxicillin + H2O
-
 Klebsiella pneumoniae NDM-7 (2R,4S)-2-[(R)-[[(2R)-2-amino-2-(4-hydroxyphenyl)acetyl]amino](carboxy)methyl]-5,5-dimethyl-1,3-thiazolidine-4-carboxylic acid
-
 ?
ampicilin + H2O
-
 Klebsiella pneumoniae (2R,4S)-2-[(R)-[[(2R)-2-amino-2-phenylacetyl]amino](carboxy)methyl]-5,5-dimethyl-1,3-thiazolidine-4-carboxylic acid
-
 ?
carbapenem + H2O
-
 Klebsiella pneumoniae [(2R)-2,3-dihydro-1H-pyrrol-2-yl]acetic acid
-
 ?
carbapenem + H2O
-
 Klebsiella pneumoniae NDM-7 [(2R)-2,3-dihydro-1H-pyrrol-2-yl]acetic acid
-
 ?
cephalothin + H2O
-
 Klebsiella pneumoniae (2R)-5-[(acetyloxy)methyl]-2-[(R)-carboxy[2-(thiophen-2-yl)acetamido]methyl]-3,6-dihydro-2H-1,3-thiazine-4-carboxylic acid
-
 ?
doripenem + H2O
-
 Klebsiella pneumoniae (4R,5S)-5-[(1S,2R)-1-carboxy-2-hydroxypropyl]-4-methyl-3-(((3S,5S)-5-[(sulfamoylamino)methyl]pyrrolidin-3-yl)sulfanyl)-4,5-dihydro-1H-pyrrole-2-carboxylic acid
-
 ?
imipenem + H2O
-
 Klebsiella pneumoniae (5R)-3-[[2-(carbonoimidoylamino)ethyl]sulfanyl]-5-[(1S,2R)-1-carboxy-2-hydroxypropyl]-4,5-dihydro-1H-pyrrole-2-carboxylic acid
-
 ?
meropenem + H2O
-
 Klebsiella pneumoniae (4R,5S)-5-[(1S,2R)-1-carboxy-2-hydroxypropyl]-3-[[(3S,5S)-5-(dimethylcarbamoyl)pyrrolidin-3-yl]sulfanyl]-4-methyl-4,5-dihydro-1H-pyrrole-2-carboxylic acid
-
 ?
additional information resistance to antibiotics of recombinant His-tagged wild-type and mutant enzymes expressed in Escherichia coli strain CS109, overview Klebsiella pneumoniae ?
-
-
additional information purified enzyme NDM-7 exhibits broad-spectrum enzyme activities with low Km and high kcat values hydrolysing all beta-lactam substrates tested Klebsiella pneumoniae ?
-
-
additional information resistance to antibiotics of recombinant His-tagged wild-type and mutant enzymes expressed in Escherichia coli strain CS109, overview Klebsiella pneumoniae NDM-7 ?
-
-
additional information purified enzyme NDM-7 exhibits broad-spectrum enzyme activities with low Km and high kcat values hydrolysing all beta-lactam substrates tested Klebsiella pneumoniae NDM-7 ?
-
-
penicillin G + H2O
-
 Klebsiella pneumoniae (2R,4S)-2-[(R)-carboxy[(phenylacetyl)amino]methyl]-5,5-dimethyl-1,3-thiazolidine-4-carboxylic acid
-
 ?
penicillin G + H2O
-
 Klebsiella pneumoniae NDM-7 (2R,4S)-2-[(R)-carboxy[(phenylacetyl)amino]methyl]-5,5-dimethyl-1,3-thiazolidine-4-carboxylic acid
-
 ?

Synonyms

Synonyms Comment Organism
blaNDM-7
-
 Klebsiella pneumoniae

General Information

General Information Comment Organism
additional information Glu152 and Ser191 are the key residues required for the metallo-beta-lactamase activity of strain NDM-7. Three-dimensional structure homology modelling of wild-type BlaNDM-7 and mutant enzymes Klebsiella pneumoniae