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Literature summary extracted from

  • Chow, C.; Xu, H.; Blanchard, J.S.
    Kinetic characterization of hydrolysis of nitrocefin, cefoxitin, and meropenem by beta-lactamase from Mycobacterium tuberculosis (2013), Biochemistry, 52, 4097-4104.
    View publication on PubMedView publication on EuropePMC

Protein Variants

EC Number Protein Variants Comment Organism
3.5.2.6 E166A site-directed mutagenesis, inactive mutant. The Glu166Ala mutant form of BlaC has no hydrolytic activity and forms a stable acyl-enzyme complex that can be structurally characterized, suggesting that Glu166 is required for deacylation and product release Mycobacterium tuberculosis
3.5.2.6 K73A site-directed mutagenesis, inactive mutant. The Lys73Ala mutant form of BlaC permits the structural identification of the Michaelis complex, but has no catalytic activity, indicating Lys73 is essential for the acylation step Mycobacterium tuberculosis

Inhibitors

EC Number Inhibitors Comment Organism Structure
3.5.2.6 clavulanate
-
 Mycobacterium tuberculosis

KM Value [mM]

EC Number KM Value [mM] KM Value Maximum [mM] Substrate Comment Organism Structure
3.5.2.6 additional information
-
 additional information pre-steady-state, stopped-flow experiments with cefoxitin, solvent kinetic isotope effects and kinetic analysis with different substrates, kinetic mechanism, overview Mycobacterium tuberculosis

Organism

EC Number Organism UniProt Comment Textmining
3.5.2.6 Mycobacterium tuberculosis P9WKD3 gene blaC
-
3.5.2.6 Mycobacterium tuberculosis H37Rv P9WKD3 gene blaC
-

Substrates and Products (Substrate)

EC Number Substrates Comment Substrates Organism Products Comment (Products) Rev. Reac.
3.5.2.6 cefoxitin + H2O high activity Mycobacterium tuberculosis (2R)-5-[(carbamoyloxy)methyl]-2-[(S)-carboxy(methoxy)[2-(thiophen-2-yl)acetamido]methyl]-3,6-dihydro-2H-1,3-thiazine-4-carboxylic acid
-
 ?
3.5.2.6 cefoxitin + H2O high activity Mycobacterium tuberculosis H37Rv (2R)-5-[(carbamoyloxy)methyl]-2-[(S)-carboxy(methoxy)[2-(thiophen-2-yl)acetamido]methyl]-3,6-dihydro-2H-1,3-thiazine-4-carboxylic acid
-
 ?
3.5.2.6 doripenem + H2O very low activity Mycobacterium tuberculosis (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
-
 ?
3.5.2.6 doripenem + H2O very low activity Mycobacterium tuberculosis H37Rv (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
-
 ?
3.5.2.6 ertapenem + H2O very low activity Mycobacterium tuberculosis (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
-
 ?
3.5.2.6 ertapenem + H2O very low activity Mycobacterium tuberculosis H37Rv (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
-
 ?
3.5.2.6 meropenem + H2O very slow substrate and low activity Mycobacterium tuberculosis (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
-
 ?
3.5.2.6 meropenem + H2O very slow substrate and low activity Mycobacterium tuberculosis H37Rv (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
-
 ?
3.5.2.6 additional information during the acylation reaction of carbapenems catalyzed by BlaC, the ring opening of the beta-lactam yields an initial DELTA2-pyrroline ring, which subsequently isomerizes to a DELTA1-pyrroline ring with stereospecific protonation at C3 to generate the final, stable acylated adduct Mycobacterium tuberculosis ?
-
 ?
3.5.2.6 additional information during the acylation reaction of carbapenems catalyzed by BlaC, the ring opening of the beta-lactam yields an initial DELTA2-pyrroline ring, which subsequently isomerizes to a DELTA1-pyrroline ring with stereospecific protonation at C3 to generate the final, stable acylated adduct Mycobacterium tuberculosis H37Rv ?
-
 ?
3.5.2.6 nitrocefin + H2O high activity Mycobacterium tuberculosis (2R)-2-[(R)-carboxy[2-(thiophen-2-yl)acetamido]methyl]-5-[(E)-2-(2,4-dinitrophenyl)ethenyl]-3,6-dihydro-2H-1,3-thiazine-4-carboxylic acid
-
 ?

Synonyms

EC Number Synonyms Comment Organism
3.5.2.6 BlaC
-
 Mycobacterium tuberculosis

Temperature Optimum [°C]

EC Number Temperature Optimum [°C] Temperature Optimum Maximum [°C] Comment Organism
3.5.2.6 25
-
 assay at Mycobacterium tuberculosis

pH Optimum

EC Number pH Optimum Minimum pH Optimum Maximum Comment Organism
3.5.2.6 7.8 8
-
 Mycobacterium tuberculosis

pH Range

EC Number pH Minimum pH Maximum Comment Organism
3.5.2.6 additional information
-
 pH dependence of the kinetic parameters, revealing that the maximum velocity depends on the ionization state of two groups: a general base exhibiting a pK value of 4.5 and a general acid exhibiting a pK value of 7.8, overview Mycobacterium tuberculosis

General Information

EC Number General Information Comment Organism
3.5.2.6 evolution BlaC is a class A beta-lactamase Mycobacterium tuberculosis
3.5.2.6 additional information the catalytic mechanism of BlaC relies on three highly conserved active site residues, Lys73 and Glu166, which are involved in the activation of the acylating nucleophile Ser70 and the activation of the active site water molecule for deacylation, respectively. Lys73 is essential for the acylation step Mycobacterium tuberculosis
3.5.2.6 physiological function the constitutively expressed, chromosomally-encoded beta-lactamase (BlaC) is the enzyme responsible for the intrinsic resistance to beta-lactam antibiotics in Mycobacterium tuberculosis Mycobacterium tuberculosis