Crystallization (Comment) | Organism |
---|---|
substrate ertapenem-isozyme GES-2 crystal structure determination and analysis | Pseudomonas aeruginosa |
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 | UniProt | Comment | Textmining |
---|---|---|---|
Pseudomonas aeruginosa | A0EL75 | gene bla GES-5 | - |
Pseudomonas aeruginosa | Q7BEB3 | gene bla GES-1 | - |
Pseudomonas aeruginosa | Q93F76 | gene bla GES-2 | - |
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 | Comment | Organism |
---|---|---|
GES-1 | - |
Pseudomonas aeruginosa |
GES-2 | - |
Pseudomonas aeruginosa |
GES-5 | - |
Pseudomonas aeruginosa |
GES-type beta-lactamase | - |
Pseudomonas aeruginosa |
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 |