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Information on EC 3.5.2.6 - beta-lactamase and Organism(s) Bacillus licheniformis and UniProt Accession P00808
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3.5.2.6 beta-lactamaseIUBMB Comments
A group of enzymes of varying specificity hydrolysing beta-lactams; some act more rapidly on penicillins, some more rapidly on cephalosporins. The latter were formerly listed as EC 3.5.2.8, cephalosporinase.
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Word Map
- 3.5.2.6
- pneumonia
- klebsiella
- enterobacteriaceae
-
esbls
- carbapenems
- aeruginosa
-
carbapenem-resistant
- ampicillin
-
esbl-producing
-
multidrug-resistant
- enterobacter
- cefotaxime
- ceftazidime
- aureus
- acinetobacter
-
surveillance
- meropenem
-
nosocomial
-
clavulanic
-
microbiological
- haemophilus
- aminoglycosides
- ciprofloxacin
- baumannii
- cloacae
- tetracycline
-
pulsed-field
-
outbreak
-
disk
- gentamicin
- integrons
-
plasmid-mediated
- colistin
- amikacin
- ceftriaxone
- fluoroquinolones
-
microdilution
-
quinolone
- citrobacter
- proteus
-
multilocus
-
carriage
- mirabilis
- gonorrhoeae
-
staphylococci
-
community-acquired
-
third-generation
- methicillin
-
penicillin-binding
-
enterococci
- drug development
- synthesis
- diagnostics
- medicine
- pharmacology
The taxonomic range for the selected organisms is: Bacillus licheniformis
The enzyme appears in selected viruses and cellular organisms
The enzyme appears in selected viruses and cellular organisms
Synonyms
beta-lactamase, carbapenemase, extended-spectrum beta-lactamase, ndm-1, penicillinase, tem-1, blandm-1, ges-1, blactx-m-15, kpc-2, 
more
topSYNONYM 
ORGANISM
UNIPROT
COMMENTARY 
LITERATURE
Beta lactamase OXA-10
-
-
-
-
beta-lactamase
-
-
-
-
beta-lactamase AME I
-
-
-
-
beta-lactamase II
-
-
-
-
BLAIMP
-
-
-
-
carbapenemase
-
-
-
-
Carbenicillinase
-
-
-
-
cefotaximase
-
-
-
-
ceftazidimase
-
-
-
-
cefurooximase
-
-
-
-
Cefuroximase
-
-
-
-
Cephalosporinase
-
-
-
-
Imipenem-cefoxitin hydrolyzing enzyme
-
-
-
-
imipenemase
-
-
-
-
metallo-beta-lactamase
-
-
-
-
neutrapen
-
-
-
-
Oxacillinase
-
-
-
-
penicillinase
-
-
-
-
SHV-2A
-
-
-
-
REACTION
REACTION DIAGRAM
COMMENTARY
ORGANISM
UNIPROT
LITERATURE
a beta-lactam + H2O = a substituted beta-amino acid
Glu166 is important for catalysis, mechanism
REACTION TYPE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
carboxylic acid amide hydrolysis
-
-
-
-
PATHWAY SOURCE
PATHWAYS
SYSTEMATIC NAME
IUBMB Comments
beta-lactam hydrolase
A group of enzymes of varying specificity hydrolysing beta-lactams; some act more rapidly on penicillins, some more rapidly on cephalosporins. The latter were formerly listed as EC 3.5.2.8, cephalosporinase.
CAS REGISTRY NUMBER
COMMENTARY
9073-60-3
-
SUBSTRATE
PRODUCT
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate)
(Substrate)
LITERATURE
(Substrate)
(Substrate)
COMMENTARY
(Product)
(Product)
LITERATURE
(Product)
(Product)
Reversibility
r=reversible
ir=irreversible
?=not specified
r=reversible
ir=irreversible
?=not specified
7-beta-formamidoyl-7-alpha-methoxycephalosporanic acid + H2O
(2R)-5-[(acetyloxy)methyl]-2-{(S)-carboxy[(E)-(hydroxymethylidene)amino]methoxymethyl}-3,6-dihydro-2H-1,3-thiazine-4-carboxylic acid
-
-
-
?
cefoxitin + H2O
(2R)-5-[(carbamoyloxy)methyl]-2-[(S)-carboxy(methoxy)[(thiophen-2-ylacetyl)amino]methyl]-3,6-dihydro-2H-1,3-thiazine-4-carboxylic acid
-
-
-
?
cefuroxime + H2O
(2R)-5-[(carbamoyloxy)methyl]-2-[(R)-carboxy{[(2Z)-2-(furan-2-yl)-2-(methoxyimino)acetyl]amino}methyl]-3,6-dihydro-2H-1,3-thiazine-4-carboxylic acid
-
-
-
?
cephalotin + H2O
(2R)-5-[(acetyloxy)methyl]-2-[(R)-carboxy[(thiophen-2-ylacetyl)amino]methyl]-3,6-dihydro-2H-1,3-thiazine-4-carboxylic acid
-
-
-
?
moxalactam + H2O
(2R)-2-{(R)-carboxy[2-carboxy(4-hydroxyphenyl)acetamido]methoxymethyl}-5-{[(1-methyl-1H-tetrazol-5-yl)sulfanyl]methyl}-3,6-dihydro-2H-1,3-oxazine-4-carboxylic acid
-
-
-
?
penicillin G + H2O
(2R,4S)-2-[(R)-carboxy[(phenylacetyl)amino]methyl]-5,5-dimethyl-1,3-thiazolidine-4-carboxylic acid
-
-
-
?
6-aminopenicillanic acid + H2O
(2R,4S)-2-[amino(carboxy)methyl]-5,5-dimethyl-1,3-thiazolidine-4-carboxylic acid
-
-
-
-
?
7-(thienyl-2-acetamido)-3-[2-(4-N,N-dimethylaminophenylazo)pyridinium-methyl]-3-cephem-4-carboxylic acid + H2O
(2R)-2-[(R)-carboxy{(E)-[1-hydroxy-2-(thiophen-2-yl)ethylidene]amino}methyl]-5-{[(2E)-2-{[4-(dimethyliminio)cyclohexa-2,5-dien-1-ylidene]hydrazinylidene}pyridin-1(2H)-yl]methyl}-3,6-dihydro-2H-1,3-thiazine-4-carboxylate
-
i.e. PADAC
-
-
?
ampicillin + H2O
(2R,4S)-2-[(R)-[[(2R)-2-amino-2-phenylacetyl]amino](carboxy)methyl]-5,5-dimethyl-1,3-thiazolidine-4-carboxylic acid
-
-
-
-
?
benzyl cephalosporin C + H2O
(2R)-5-[(acetyloxy)methyl]-2-[(R)-{[(5R)-5-amino-6-(benzyloxy)-6-oxohexanoyl]amino}(carboxy)methyl]-3,6-dihydro-2H-1,3-thiazine-4-carboxylic acid
-
-
-
-
?
benzylpenicillin + H2O
(2R,4S)-2-[(R)-carboxy(2-phenylacetamido)methyl]-5,5-dimethyl-1,3-thiazolidine-4-carboxylic acid
-
-
-
-
?
cephalosporin C + H2O
N6-[(R)-{(2R)-5-[(acetyloxy)methyl]-4-carboxy-3,6-dihydro-2H-1,3-thiazin-2-yl}(carboxy)methyl]-6-oxo-D-lysine
-
-
-
-
?
methicillin + H2O
(2R,4S)-2-[(R)-carboxy(2,6-dimethoxybenzamido)methyl]-5,5-dimethyl-1,3-thiazolidine-4-carboxylic acid
nitrocefin + H2O
(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
-
-
-
-
?
phenoxymethylpenicillin + H2O
(2R,4S)-2-[(R)-carboxy(2-phenoxyacetamido)methyl]-5,5-dimethyl-1,3-thiazolidine-4-carboxylic acid
-
-
-
-
?
methicillin + H2O
(2R,4S)-2-[(R)-carboxy(2,6-dimethoxybenzamido)methyl]-5,5-dimethyl-1,3-thiazolidine-4-carboxylic acid
-
-
-
-
?
methicillin + H2O
(2R,4S)-2-[(R)-carboxy(2,6-dimethoxybenzamido)methyl]-5,5-dimethyl-1,3-thiazolidine-4-carboxylic acid
-
-
-
-
ir
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
cefoxitin
perturbs the active site structure and the conformation of the omega-loop bearing the catalytic residue Glu166, inhibition mechanism
lactivicin
inhibits penicillin-binding proteins and serine beta-lactamases
KM VALUE [mM]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
0.14
7-(thienyl-2-acetamido)-3-[2-(4-,N,N-dimethylaminophenylazo)pyridinium-methyl]-3-cephem-4-carboxylic acid
-
wild type
0.0079
penicillin G
mutant E166C, carrying 6-bromoacetyl-2-dimethylaminonaphthalene label, pH 7.0, 22°C
TURNOVER NUMBER [1/s]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
667
7-(thienyl-2-acetamido)-3-[2-(4-,N,N-dimethylaminophenylazo)pyridinium-methyl]-3-cephem-4-carboxylic acid
-
-
0.32
penicillin G
mutant E166C, carrying 6-bromoacetyl-2-dimethylaminonaphthalene label, pH 7.0, 22°C
kcat/KM VALUE [1/mMs-1]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
40
penicillin G
mutant E166C, carrying 6-bromoacetyl-2-dimethylaminonaphthalene label, pH 7.0, 22°C
SPECIFIC ACTIVITY [µmol/min/mg]
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
pH OPTIMUM
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
6.5
pH RANGE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
4 - 9
-
substrate phenoxymethylpenicillin: kcat 1/6 at pH 9 compared to pH 6.5
TEMPERATURE OPTIMUM
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
TEMPERATURE RANGE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
50 - 75
-
pH 7: stable up to 58, 62, 68°C for K234E, wild type and K234A respectively
ORGANISM
COMMENTARY
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
LOCALIZATION
ORGANISM
UNIPROT
COMMENTARY
GeneOntology No.
LITERATURE
SOURCE
UNIPROT
ENTRY NAME
ORGANISM
NO. OF AA
NO. OF TRANSM. HELICES
MOLECULAR WEIGHT[Da]
SOURCE
SEQUENCE
LOCALIZATION PREDICTION
The reliability class of the localization prediction ranges from 1 (very reliable) to 5 (not reliable).
The reliability class of the localization prediction ranges from 1 (very reliable) to 5 (not reliable). PDB
SCOP
CATH
UNIPROT
ORGANISM
MOLECULAR WEIGHT
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
29000
SUBUNIT
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
POSTTRANSLATIONAL MODIFICATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
CRYSTALLIZATION (Commentary)
ORGANISM
UNIPROT
LITERATURE
purified recombinant enzyme, complexed with cefoxitin in an acyl-enzyme-adduct, for monoclinic crystals: 0.005 ml protein solution, 10 mg/ml, + equal volume of reservoir solution containing 25% PEG 6000, 0.1 M sodium acetate, pH 5.0, against 1 ml of reservoir solution at 20°C, for very big prismatic crystals: 40 mg/ml protein with lowered PEG 6000 concentration, pH 3.4, complexing by diffusion of cefoxitin for 24 h, X-ray diffraction structure determination and analysis at 1.7 A resolution
PROTEIN VARIANTS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
E166C
mutant constructed to obtain an engineered beta-lactamase that contains an environment-sensitive fluorophore conjugated near its active site to probe the structural dynamics of the omega-loop and to detect the binding of substrates. Mutant enzyme carrying a 6-bromoacetyl-2-dimethylaminonaphthalene label shows improved binding kinetics and positive fluorescence signal toward oxyimino-cephalosporins, but shows little such effect to non-oxyimino-cephalosporins. The omega-loop adopts a less stabilized structure, and readily undergoes conformational change to accommodate the binding of bulky oxyimino-cephalosporins while no such change is observed for non-oxyimino-cephalosporins
K234A
-
no significant structural change, mutant with decreased Km 1-2 orders of magnitude and kcat 2-3 orders of magnitude
K234E
-
no significant structural change, mutant with decreased Km 1-2 orders of magnitude and kcat 2-3 orders of magnitude
additional information
additional information
replacement, separately or simultaneously, three of the ESBL alpha helices with prototype amphiphatic helices from a catalog of secondary structure elements. Although the substitutes bear no sequence similarity to the originals and pertain to unrelated protein families, all the engineered ESBL variants fold in native like structures with in vitro and in vivo enzymic activity. The triple substituted variant resembles a primitive protein, with folding defects such as a strong tendency to oligomerization and very low stability. It mimics a non homologous recombinant abandoning the family sequence space while preserving fold
additional information
-
replacement, separately or simultaneously, three of the ESBL alpha helices with prototype amphiphatic helices from a catalog of secondary structure elements. Although the substitutes bear no sequence similarity to the originals and pertain to unrelated protein families, all the engineered ESBL variants fold in native like structures with in vitro and in vivo enzymic activity. The triple substituted variant resembles a primitive protein, with folding defects such as a strong tendency to oligomerization and very low stability. It mimics a non homologous recombinant abandoning the family sequence space while preserving fold
PURIFICATION (Commentary)
ORGANISM
UNIPROT
LITERATURE
CLONED (Commentary)
ORGANISM
UNIPROT
LITERATURE
expressed in Escherichia coli, Bacillus subtilis, Bacillus stearothermophilus
-
REF.
AUTHORS
TITLE
JOURNAL
VOL.
PAGES
YEAR
ORGANISM (UNIPROT)
PUBMED ID
SOURCE
Yamamoto, S.; Lampen, J.O.
Purification of plasma membrane penicillinase from Bacillus licheniformis 749/C and comparison with exoenzyme
J. Biol. Chem.
251
4095-4101
1976
Bacillus licheniformis, Bacillus licheniformis 749/C
Thatcher, D.R.
beta-Lactamase (Bacillus licheniformis)
Methods Enzymol.
43
652-664
1975
Bacillus licheniformis, Bacillus licheniformis 749/C, Bacillus licheniformis 6346/C
-
Citri, N.
Penicillinase and other beta-lactamases
The Enzymes, 3rd Ed. (Boyer, P. D. , ed. )
4
23-46
1971
Enterobacter cloacae, Bacillus cereus, Bacillus licheniformis, Escherichia coli, Staphylococcus aureus
-
Ledent, P.; Duez, C.; Vanhove, M.; Lejeune, A.; Fonze, E.; Charlier, P.; Rhazi-Filali, F.; Thamm, I.; Guillaume, G.; Samyn, B.; Devreese, B.; Van Beeumen, J.; Lamotte-Brasseur, J.; Frere, J.M.
Unexpected influence of a C-terminal His-tag on the processing of an enzyme and on the kinetic and folding parameters
FEBS Lett.
413
194-196
1997
Bacillus licheniformis, Bacillus licheniformis BS3
Wang, H.Y.; Zhang, M.; Imanaka, T.
Screening and separation of beta-lactam antibiotics using protein-engineered enzymes
Ann. N. Y. Acad. Sci.
613
376-384
1990
Bacillus licheniformis, Streptomyces sp.
Ellerby, L.M.; Escobar, W.A.; Fink, A.L.; Mitchinson, C.; Wells, J.A.
The role of lysine-234 in beta-lactamase catalysis probed by site directed mutagenesis
Biochemistry
29
5797-5806
1990
Bacillus licheniformis
Fonze, E.; Vanhove, M.; Dive, G.; Sauvage, E.; Frere, J.M.; Charlier, P.
Crystal structures of the Bacillus licheniformis BS3 class A beta-lactamase and of the acyl-enzyme adduct formed with cefoxitin
Biochemistry
41
1877-1885
2002
Bacillus licheniformis (P00808)
Brown, T.; Charlier, P.; Herman, R.; Schofield, C.J.; Sauvage, E.
Structural basis for the interaction of lactivicins with serine beta-lactamases
J. Med. Chem.
53
5890-5894
2010
Bacillus licheniformis (P94458)
Risso, V.A.; Primo, M.E.; Ermacora, M.R.
Re-engineering a beta-lactamase using prototype peptides from a library of local structural motifs
Protein Sci.
18
440-449
2009
Bacillus licheniformis (P00808), Bacillus licheniformis
Wong, W.T.; Chan, K.C.; So, P.K.; Yap, H.K.; Chung, W.H.; Leung, Y.C.; Wong, K.Y.; Zhao, Y.
Increased structural flexibility at the active site of a fluorophore-conjugated beta-lactamase distinctively impacts its binding toward diverse cephalosporin antibiotics
J. Biol. Chem.
286
31771-31780
2011
Bacillus licheniformis (P00808)
EXTERNAL LINKS (specific for EC-Number 3.5.2.6)
Transporter Classification Database (TCDB): 9.B.29.2.7
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