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Information on EC 3.5.2.6 - beta-lactamase and Organism(s) Serratia marcescens and UniProt Accession P52699
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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: Serratia marcescens
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
-
-
-
-
metallo-beta-lactamase
-
-
-
-
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
benzylpenicillin + H2O
(2R,4S)-2-[(R)-carboxy(2-phenylacetamido)methyl]-5,5-dimethyl-1,3-thiazolidine-4-carboxylic acid
-
-
-
?
cephaloridine + H2O
(2R)-2-[(R)-carboxy[(thiophen-2-ylacetyl)amino]methyl]-5-(pyridinium-1-ylmethyl)-3,6-dihydro-2H-1,3-thiazine-4-carboxylate
-
-
-
?
imipenem + H2O
(5R)-5-[(1S,2R)-1-carboxy-2-hydroxypropyl]-3-({2-[(iminomethyl)amino]ethyl}sulfanyl)-4,5-dihydro-1H-pyrrole-2-carboxylic acid
-
-
-
?
meropenem + H2O
(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
nitrocefin + H2O
(2R)-2-[(R)-carboxy[(thiophen-2-ylacetyl)amino]methyl]-5-[(E)-2-(2,4-dinitrophenyl)ethenyl]-3,6-dihydro-2H-1,3-thiazine-4-carboxylic acid
IMP-1 does not stabilize a nitrocefin-derived reaction intermediate, rather, the enzyme follows a simple Michaelis mechanism to hydrolyze nitrocefin
-
-
?
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
-
-
-
?
ampicillin + H2O
(2R,4S)-2-[(R)-[[(2R)-2-amino-2-phenylacetyl]amino](carboxy)methyl]-5,5-dimethyl-1,3-thiazolidine-4-carboxylic acid
-
-
-
-
?
benzylpenicillin + H2O
(2R,4S)-2-[(R)-carboxy(2-phenylacetamido)methyl]-5,5-dimethyl-1,3-thiazolidine-4-carboxylic acid
-
-
-
-
?
carbenicillin + H2O
(2R,4S)-2-{(R)-carboxy[2-carboxy(phenyl)acetamido]methyl}-5,5-dimethyl-1,3-thiazolidine-4-carboxylic acid
-
-
-
-
?
cefazolin + H2O
(2R)-2-[(R)-carboxy[(1H-tetrazol-1-ylacetyl)amino]methyl]-5-[[(5-methyl-1,3,4-thiadiazol-2-yl)sulfanyl]methyl]-3,6-dihydro-2H-1,3-thiazine-4-carboxylic acid
-
-
-
-
?
cefotaxime + H2O
(2R)-5-[(acetyloxy)methyl]-2-[(R)-[[(2E)-2-(2-amino-1,3-thiazol-4-yl)-2-(methoxyimino)acetyl]amino](carboxy)methyl]-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
-
-
-
-
?
ceftazidime + H2O
(2R)-2-[(R)-{[(2Z)-2-(2-amino-1,3-thiazol-4-yl)-2-{[(2-carboxypropan-2-yl)oxy]imino}acetyl]amino}(carboxy)methyl]-5-[(pyridin-1-ium-1-yl)methyl]-3,6-dihydro-2H-1,3-thiazine-4-carboxylate
-
cephalosporin antibiotic
-
-
?
cephalexin + H2O
(2R)-2-[(R)-[[(2R)-2-amino-2-phenylacetyl]amino](carboxy)methyl]-5-methyl-3,6-dihydro-2H-1,3-thiazine-4-carboxylic acid
-
-
-
-
?
cloxacillin + H2O
(2R,4S)-2-[(R)-carboxy{[3-(2-chlorophenyl)-5-methyl-1,2-oxazole-4-carbonyl]amino}methyl]-5,5-dimethyl-1,3-thiazolidine-4-carboxylic acid
-
-
-
-
?
imipenem + H2O
(5R)-5-[(1S,2R)-1-carboxy-2-hydroxypropyl]-3-({2-[(iminomethyl)amino]ethyl}sulfanyl)-4,5-dihydro-1H-pyrrole-2-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
-
-
-
-
?
oxacillin + H2O
(2R,4S)-2-{(R)-carboxy[(5-methyl-3-phenyl-1,2-oxazole-4-carbonyl)amino]methyl}-5,5-dimethyl-1,3-thiazolidine-4-carboxylic acid
-
-
-
-
?
meropenem + H2O
(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
-
-
-
?
meropenem + H2O
(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
meropenem enzyme-bound structure with Zn2+, PDB ID 5AXO
-
-
?
imipenem + H2O
(5R)-5-[(1S,2R)-1-carboxy-2-hydroxypropyl]-3-({2-[(iminomethyl)amino]ethyl}sulfanyl)-4,5-dihydro-1H-pyrrole-2-carboxylic acid
-
-
-
-
?
imipenem + H2O
(5R)-5-[(1S,2R)-1-carboxy-2-hydroxypropyl]-3-({2-[(iminomethyl)amino]ethyl}sulfanyl)-4,5-dihydro-1H-pyrrole-2-carboxylic acid
-
beta-lactam antibiotic
-
-
?
NATURAL SUBSTRATE
NATURAL 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
meropenem + H2O
(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
-
-
-
?
METALS and IONS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
Co2+
UV-vis studies on IMP-1 containing 1 equivalent of Co(II) show a strong ligand-to-metal charge transition at 340 nm, and the intensity of this feature increases when the second equivalent of Co(II) is added to the enzyme
Zinc
the Zn-Zn distance in D120E mutant is increased by 0.3 A compared with wild-type enzyme
Zn2+
additional information
metal-binding to metal-free IMP-1 follows a positive-cooperative mode
Zn2+
a di-zinc enzyme, meropenem enzyme-bound structure with Zn2+, PDB ID 5AXO, overview. Zn1 and Zn2 at the active site pocket bind in a distance of 3.5A. The zinc ions are involved in inhibitor binding
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
eupalitin
binding to the enzyme involves residues Leu176, Thr177, Leu196, Ile245, and Leu253
Imipenem
binding to the enzyme involves residues His72, His74, His150, His215, and Arg252
L-captopril
binding to the enzyme involves residues His72, His74, Asp76, His77, and His150
luteolin
binding to the enzyme involves residues His72, HIS74, Phe114, His150, and Pro216
phosphate
competitive inhibition. 50 mM, 30% decrease of wild-type activity. 5 mM, 90% decrease of activity of mutant enzyme D120A
rosmarinic acid
binding to the enzyme involves residues Thr177, Ala178, Val179, Val218, and Ile245
beta-lactamase inhibitor protein
-
i.e. BLIP, 17 kDa protein produced by Streptomyces clavuligerus, specific for class A enzymes, construction of diverse mutants of BLIP for identification of functional epitopes, enzyme-inhibitor complex modeling
-
clavulanate
-
62.2-92.1% of activity is inhibited after preincubation with 0.1 mM clavulanate
EDTA
-
0.1 mM EDTA inhibits only 4.8-26.8% of the activity of the TEM-type beta-lactamase
N-[2-(7-chloro-quinolin-4-ylamino)-ethyl]-3-mercapto-propionamide
-
IC50: 0.0142 mM
N-[3-(7-chloro-quinolin-4-ylamino)-propyl]-3-mercapto-propionamide
-
IC50: 0.0066 mM
N-[4-(7-chloro-quinolin-4-ylamino)-butyl]-3-mercapto-propionamide
-
IC50: 0.0025 mM
N-[5-(7-chloro-quinolin-4-ylamino)-pentyl]-3-mercapto-propionamide
-
IC50: 0.0067 mM
N-[6-(7-cloro-quinolin-4-ylamino)-hexyl]-3-mercapto-propionamide
-
IC50: 0.0034 mM
additional information
dynamic behavior of the enzyme over simulation time with natural inhibitors using molecular dynamics studies, molecular docking, overview. The zinc ions are involved in inhibitor binding. Inhibitor binding alters the enzyme conformation. The natural inhibitors impairs the substrate binding by occupying a part of enzyme active site
-
additional information
-
shows high-level resistance to expanded-spectrum cephalosporins and beta-lactam clavulanate combinations
-
KM VALUE [mM]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
0.0017
benzylpenicillin
-
at 30°C in 50 mM sodium phosphate buffer (pH 7.0)
additional information
additional information
enzyme kinetics and thermodynamics
-
TURNOVER NUMBER [1/s]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
Ki VALUE [mM]
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
0.0000024
beta-lactamase inhibitor protein
-
wild-type inhibitor protein, pH 7.5, 25°C
-
additional information
additional information
-
Ki for diverse mutants of beta-lactamase inhibitor protein BLIP, overview
-
IC50 VALUE [mM]
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
0.0142
N-[2-(7-chloro-quinolin-4-ylamino)-ethyl]-3-mercapto-propionamide
Serratia marcescens
-
IC50: 0.0142 mM
0.0066
N-[3-(7-chloro-quinolin-4-ylamino)-propyl]-3-mercapto-propionamide
Serratia marcescens
-
IC50: 0.0066 mM
0.0025
N-[4-(7-chloro-quinolin-4-ylamino)-butyl]-3-mercapto-propionamide
Serratia marcescens
-
IC50: 0.0025 mM
0.0067
N-[5-(7-chloro-quinolin-4-ylamino)-pentyl]-3-mercapto-propionamide
Serratia marcescens
-
IC50: 0.0067 mM
0.0034
N-[6-(7-cloro-quinolin-4-ylamino)-hexyl]-3-mercapto-propionamide
Serratia marcescens
-
IC50: 0.0034 mM
ORGANISM
COMMENTARY
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
SOURCE TISSUE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
SOURCE
GENERAL INFORMATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
physiological function
metallo-beta-lactamase (MBL) is a class of enzyme that catalyzes the hydrolysis of a broad range of beta-lactam antibiotics leading to the development of drug resistance in bacteria
physiological function
-
subclass B3 metallo-beta-lactamase SMB-1 that confers carbapenem resistance
additional information
structure-function analysis, molecular dynamics simulation and modeling, overview
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
CRYSTALLIZATION (Commentary)
ORGANISM
UNIPROT
LITERATURE
hanging-drop vapour diffusion method. Three-dimensional structures of D120A mutant and D120E mutant determined at 2.0 A and 3.0 A resolution, respectively
hanging drop vapour diffusion method with 20% poly(ethylene)glycol 6 K in 0.1 M Tris (pH 8.0)
-
purified recombinant His-tagged enzyme, method screening, sitting drop vapour diffusion method, mixing of 0.001 ml protein solution with 0.001 ml reservoir solution containing 0.2 M ammonium sulfate, 0.1 M sodium acetate trihydrate, pH 5.3, 28% w/v PEG MME 2000, or 1.0 M lithium chloride, 0.1 M MES, pH 5.8, and 26% w/v PEG 6000, 1 week, 20°C, resulting in two different types of crystals: SMB-1a and SMB-1b, X-ray diffraction structure determination and analysis at 1.60-1.63 A resolution, molecular replacement and modeling
-
PROTEIN VARIANTS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
D120A
kcat/KM is up to 425000fold lower than the wild-type enzyme. Ki-value for phosphate is 450fold lower than wild-type value
D120E
kcat/KM is up to 136000fold lower than the wild-type enzyme. the Zn-Zn distance is increased by 0.3 A compared with wild-type enzyme
additional information
-
construction of diverse mutants of the beta-lactamase inhibitor protein BLIP by alanine scanning mutation
PURIFICATION (Commentary)
ORGANISM
UNIPROT
LITERATURE
recombinant His-tagged enzyme from Escherichia coli strain BL21(DE3)pLysS by nickel affinity chromatography and two different steps of gel filtration, followed by diafiltration
-
CLONED (Commentary)
ORGANISM
UNIPROT
LITERATURE
gene SMB-1, recombinant expression of Hhis-tagged enzyme in Escherichia coli strain BL21(DE3)pLysS
-
APPLICATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
medicine
-
putative development of a screening of MBL producing strains by routine clinical microbiology laboratories. The detection of the MBL phenotype of resistance is of crucial importance for selecting the most appropriate therapy and applying infection control measures
REF.
AUTHORS
TITLE
JOURNAL
VOL.
PAGES
YEAR
ORGANISM (UNIPROT)
PUBMED ID
SOURCE
Zhang, Z.; Palzkill, T.
Dissecting the protein-protein interface between beta-lactamase inhibitory protein and class A beta-lactamases
J. Biol. Chem.
279
42860-42866
2004
Bacillus anthracis, Serratia marcescens, Klebsiella pneumoniae (P0AD64), Escherichia coli (P62593)
Jin, W.; Arakawa, Y.; Yasuzawa, H.; Taki, T.; Hashiguchi, R.; Mitsutani, K.; Shoga, A.; Yamaguchi, Y.; Kurosaki, H.; Shibata, N.; Ohta, M.; Goto, M.
Comparative study of the inhibition of metallo-beta-lactamases (IMP-1 and VIM-2) by thiol compounds that contain a hydrophobic group
Biol. Pharm. Bull.
27
851-856
2004
Pseudomonas aeruginosa, Serratia marcescens
Yamaguchi, Y.; Kuroki, T.; Yasuzawa, H.; Higashi, T.; Jin, W.; Kawanami, A.; Yamagata, Y.; Arakawa, Y.; Goto, M.; Kurosaki, H.
Probing the role of Asp-120(81) of metallo-beta-lactamase (IMP-1) by site-directed mutagenesis, kinetic studies, and X-ray crystallography
J. Biol. Chem.
280
20824-20832
2005
Serratia marcescens (P52699)
Kurosaki, H.; Yamaquchi, Y.; Yasuzawa, H.; Jin, W.; Yamagata, Y.; Arakawa, Y.
Probing, inhibition, and crystallographic characterization of metallo-beta -lactamase (IMP-1) with fluorescent agents containing dansyl and thiol groups
ChemMedChem
1
969-972
2006
Serratia marcescens (P52699)
Zhao, W.H.; Hu, Z.Q.; Chen, G.; Ito, R.; Shimamura, T.
Hyperproduction of inhibitor-susceptible TEM beta-lactamase is responsible for resistance of Serratia marcescens to beta-lactam-beta-lactamase inhibitor combinations
Chemotherapy
54
31-37
2008
Serratia marcescens
Michaux, C.; Massant, J.; Kerff, F.; Frere, J.M.; Docquier, J.D.; Vandenberghe, I.; Samyn, B.; Pierrard, A.; Feller, G.; Charlier, P.; Van Beeumen, J.; Wouters, J.
Crystal structure of a cold-adapted class C beta-lactamase
FEBS J.
275
1687-1697
2008
Psychrobacter immobilis, Serratia marcescens, Enterobacter cloacae (P05364), Pseudomonas fluorescens (P85302), Pseudomonas fluorescens, Pseudomonas fluorescens TAE4 (P85302), Enterobacter cloacae 908R (P05364)
Zhao, W.H.; Hu, Z.Q.; Chen, G.; Matsushita, K.; Fukuchi, K.; Shimamura, T.
Characterization of imipenem-resistant Serratia marcescens producing IMP-type and TEM-type beta-lactamases encoded on a single plasmid
Microbiol. Res.
162
46-52
2007
Serratia marcescens
Picao, R.C.; Andrade, S.S.; Nicoletti, A.G.; Campana, E.H.; Moraes, G.C.; Mendes, R.E.; Gales, A.C.
Metallo-beta-Lactamase detection: comparative evaluation of double-disk synergy versus combined disk tests for IMP, GIM, SIM, SPM or VIM-producing isolates
J. Clin. Microbiol.
46
2028-2037
2008
Acinetobacter sp., Enterobacter cloacae, Klebsiella pneumoniae, Pseudomonas aeruginosa, Pseudomonas putida, Serratia marcescens
Griffin, D.H.; Richmond, T.K.; Sanchez, C.; Moller, A.J.; Breece, R.M.; Tierney, D.L.; Bennett, B.; Crowder, M.W.
Structural and kinetic studies on metallo-beta-lactamase IMP-1
Biochemistry
50
9125-9134
2011
Serratia marcescens (P52699)
Wachino, J.; Yamaguchi, Y.; Mori, S.; Yamagata, Y.; Arakawa, Y.; Shibayama, K.
Crystallization and preliminary X-ray analysis of the subclass B3 metallo-beta-lactamase SMB-1 that confers carbapenem resistance
Acta Crystallogr. Sect. F
68
343-346
2012
Serratia marcescens
Gangadharappa, B.S.; Sharath, R.; Revanasiddappa, P.D.; Chandramohan, V.; Balasubramaniam, M.; Vardhineni, T.P.
Structural insights of metallo-beta-lactamase revealed an effective way of inhibition of enzyme by natural inhibitors
J. Biomol. Struct. Dyn.
38
3757-3771
2019
Serratia marcescens (P52699)
EXTERNAL LINKS (specific for EC-Number 3.5.2.6)
Transporter Classification Database (TCDB): 9.B.29.2.7
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