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Literature summary for 3.5.2.6 extracted from

  • Stewart, N.K.; Smith, C.A.; Frase, H.; Black, D.J.; Vakulenko, S.B.
    Kinetic and structural requirements for carbapenemase activity in GES-type beta-lactamases (2015), Biochemistry, 54, 588-597.
    View publication on PubMedView publication on EuropePMC

Crystallization (Commentary)

Crystallization (Comment) Organism
substrate ertapenem-isozyme GES-2 crystal structure determination and analysis Pseudomonas aeruginosa

Natural Substrates/ Products (Substrates)

Natural Substrates Organism Comment (Nat. Sub.) Natural Products Comment (Nat. Pro.) Rev. Reac.
doripenem + H2O Pseudomonas aeruginosa
-
(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
-
?
ertapenem + H2O Pseudomonas aeruginosa
-
(4R,5S)-5-[(1S,2R)-1-carboxy-2-hydroxypropyl]-3-([(3S,5S)-5-[(3-carboxyphenyl)carbamoyl]pyrrolidin-3-yl]sulfanyl)-4-methyl-4,5-dihydro-1H-pyrrole-2-carboxylic acid
-
?
meropenem + H2O Pseudomonas aeruginosa
-
(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
-
?

Organism

Organism UniProt Comment Textmining
Pseudomonas aeruginosa A0EL75 gene bla GES-5
-
Pseudomonas aeruginosa Q7BEB3 gene bla GES-1
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Pseudomonas aeruginosa Q93F76 gene bla GES-2
-

Substrates and Products (Substrate)

Substrates Comment Substrates Organism Products Comment (Products) Rev. Reac.
doripenem + H2O
-
Pseudomonas aeruginosa (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
-
?
ertapenem + H2O
-
Pseudomonas aeruginosa (4R,5S)-5-[(1S,2R)-1-carboxy-2-hydroxypropyl]-3-([(3S,5S)-5-[(3-carboxyphenyl)carbamoyl]pyrrolidin-3-yl]sulfanyl)-4-methyl-4,5-dihydro-1H-pyrrole-2-carboxylic acid
-
?
imipenem + H2O
-
Pseudomonas aeruginosa (5R)-5-[(1S,2R)-1-carboxy-2-hydroxypropyl]-3-([2-[(iminomethyl)amino]ethyl]sulfanyl)-4,5-dihydro-1H-pyrrole-2-carboxylic acid
-
?
meropenem + H2O
-
Pseudomonas aeruginosa (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 a single amino acid difference at position 170 of the GES-1, GES-2, and GES-5 enzymes is responsible for the expansion of their substrate profile to include carbapenem antibiotics. The catalytic efficiency of the enzymes with carbapenems meropenem, ertapenem, and doripenem progressively increases 100fold from GES-1 to -5, mainly due to an increase in the rate of acylation. While acylation is rate limiting for GES-1 and GES-2 for all three carbapenems, acylation and deacylation are indistinguishable for GES-5. Only the core structure of the antibiotic interacts with the active site of the GES-2 beta-lactamase. The identical core structures of ertapenem, doripenem, and meropenem are likely responsible for the observed similarities in the kinetics with these carbapenems. The lack of a methyl group in the core structure of imipenem may provide a structural rationale for the increase in turnover of this carbapenem by the GES beta-lactamases Pseudomonas aeruginosa ?
-
?
additional information a single amino acid difference at position 170 of the GES-1, GES-2, and GES-5 enzymes is responsible for the expansion of their substrate profile to include carbapenem antibiotics. The catalytic efficiency of the enzymes with carbapenems meropenem, ertapenem, and doripenem progressively increases 100fold from GES-1 to -5, mainly due to an increase in the rate of acylation. While acylation is rate limiting for GES-1 and GES-2 for all three carbapenems, acylation and deacylation are indistinguishable for GES-5. The identical core structures of ertapenem, doripenem, and meropenem are likely responsible for the observed similarities in the kinetics with these carbapenems. The lack of a methyl group in the core structure of imipenem may provide a structural rationale for the increase in turnover of this carbapenem by the GES beta-lactamases Pseudomonas aeruginosa ?
-
?

Synonyms

Synonyms Comment Organism
GES-1
-
Pseudomonas aeruginosa
GES-2
-
Pseudomonas aeruginosa
GES-5
-
Pseudomonas aeruginosa
GES-type beta-lactamase
-
Pseudomonas aeruginosa

General Information

General Information Comment Organism
additional information in GES-2 an extensive hydrogen-bonding network between the acyl-enzyme complex and the active site water attenuates activation of this water molecule, which results in poor deacylation by this enzyme Pseudomonas aeruginosa
physiological function GES beta-lactamases are important contributors to carbapenem resistance in clinical bacterial pathogens Pseudomonas aeruginosa