Literature summary for 3.5.2.6 extracted from

Makena, A.; Brem, J.; Pfeffer, I.; Geffen, R.E.; Wilkins, S.E.; Tarhonskaya, H.; Flashman, E.; Phee, L.M.; Wareham, D.W.; Schofield, C.J.
Biochemical characterization of New Delhi metallo-beta-lactamase variants reveals differences in protein stability (2015), J. Antimicrob. Chemother., 70, 463-469.

Cloned(Commentary)

Cloned (Comment)	Organism
gene blaNDM-1, genotyping, recombinant N-terminally His6-tagged enzyme expression in Escherichia coli strain BL21(DE3)	Klebsiella pneumoniae
gene blaNDM-10, genotyping, recombinant expression of N-terminally His6-tagged enzyme in Escherichia coli strain BL21(DE3)	Klebsiella pneumoniae
gene blaNDM-12, genotyping, recombinant expression of N-terminally His6-tagged enzyme in Escherichia coli strain BL21(DE3)	Escherichia coli
gene blaNDM-2, genotyping, recombinant expression of His6-tagged enzyme in Escherichia coli strain BL21(DE3)	Acinetobacter baumannii
gene blaNDM-3, genotyping, recombinant expression of N-terminally His6-tagged enzyme in Escherichia coli strain BL21(DE3)	Escherichia coli
gene blaNDM-4, genotyping, recombinant expression of N-terminally His6-tagged enzyme in Escherichia coli strain BL21(DE3)	Escherichia coli
gene blaNDM-5, genotyping, recombinant expression of N-terminally His6-tagged enzyme in Escherichia coli strain BL21(DE3)	Escherichia coli
gene blaNDM-6, genotyping, recombinant expression of N-terminally His6-tagged enzyme in Escherichia coli strain BL21(DE3)	Escherichia coli
gene blaNDM-7, genotyping, recombinant expression of N-terminally His6-tagged enzyme in Escherichia coli strain BL21(DE3)	Escherichia coli
gene blaNDM-8, genotyping, recombinant expression of N-terminally His6-tagged enzyme in Escherichia coli strain BL21(DE3)	Escherichia coli
gene blaNDM-9, genotyping, recombinant expression of N-terminally His6-tagged enzyme in Escherichia coli strain BL21(DE3)	Klebsiella pneumoniae

Protein Variants

Protein Variants	Comment	Organism
A233V	naturally occuring genetic variant	Escherichia coli
D130G/M154L	naturally occuring genetic variation	Escherichia coli
D130N/M154L	naturally occuring genetic variation	Escherichia coli
D95N	naturally occuring genetic variation	Escherichia coli
E152K	naturally occuring genetic variation	Klebsiella pneumoniae
G69S/A74T/G200R	naturally occuring genetic variation	Klebsiella pneumoniae
M154L	naturally occuring genetic variation	Escherichia coli
M154L/G222D	naturally occuring genetic variation	Escherichia coli
P28A	naturally occuring genetic variation, the P28A substitution occurs in the predicted N-terminal periplasmic signal peptide	Acinetobacter baumannii
V88L/M154L	naturally occuring genetic variation	Escherichia coli

Inhibitors

Inhibitors	Comment	Organism	Structure
nitrocefin	substrate inhibition; substrate inhibition; substrate inhibition; substrate inhibition	Escherichia coli

KM Value [mM]

KM Value [mM]	KM Value Maximum [mM]	Substrate	Comment	Organism
0.004	-	nitrocefin	pH 7.2, 25°C, recombinant enzyme	Escherichia coli
0.005	-	nitrocefin	pH 7.2, 25°C, recombinant enzyme	Escherichia coli
0.005	-	cefalotin	pH 7.2, 25°C, recombinant enzyme	Escherichia coli
0.006	-	nitrocefin	pH 7.2, 25°C, recombinant enzyme	Escherichia coli
0.008	-	nitrocefin	pH 7.2, 25°C, recombinant enzyme	Escherichia coli
0.01	-	cefalotin	pH 7.2, 25°C, recombinant enzyme	Escherichia coli
0.011	-	nitrocefin	pH 7.2, 25°C, recombinant enzyme	Klebsiella pneumoniae
0.011	-	cefalotin	pH 7.2, 25°C, recombinant enzyme	Escherichia coli
0.013	-	cefalotin	pH 7.2, 25°C, recombinant enzyme	Escherichia coli
0.015	-	cefalotin	pH 7.2, 25°C, recombinant enzyme	Escherichia coli
0.016	-	cefoxitin	pH 7.2, 25°C, recombinant enzyme	Escherichia coli
0.019	-	ceftazidime	pH 7.2, 25°C, recombinant enzyme	Escherichia coli
0.02	-	Imipenem	pH 7.2, 25°C, recombinant enzyme	Escherichia coli
0.023	-	cefoxitin	pH 7.2, 25°C, recombinant enzyme	Escherichia coli
0.027	-	cefoxitin	pH 7.2, 25°C, recombinant enzyme	Escherichia coli
0.029	-	cefalotin	pH 7.2, 25°C, recombinant enzyme	Klebsiella pneumoniae
0.043	-	cefoxitin	pH 7.2, 25°C, recombinant enzyme	Klebsiella pneumoniae
0.045	-	meropenem	pH 7.2, 25°C, recombinant enzyme	Escherichia coli
0.049	-	meropenem	pH 7.2, 25°C, recombinant enzyme	Escherichia coli
0.05	-	cefoxitin	pH 7.2, 25°C, recombinant enzyme	Escherichia coli
0.054	-	meropenem	pH 7.2, 25°C, recombinant enzyme	Escherichia coli
0.056	-	Imipenem	pH 7.2, 25°C, recombinant enzyme	Escherichia coli
0.057	-	meropenem	pH 7.2, 25°C, recombinant enzyme	Klebsiella pneumoniae
0.058	-	meropenem	pH 7.2, 25°C, recombinant enzyme	Escherichia coli
0.062	-	Imipenem	pH 7.2, 25°C, recombinant enzyme	Escherichia coli
0.063	-	cefoxitin	pH 7.2, 25°C, recombinant enzyme	Escherichia coli
0.064	-	doripenem	pH 7.2, 25°C, recombinant enzyme	Escherichia coli
0.078	-	Imipenem	pH 7.2, 25°C, recombinant enzyme	Klebsiella pneumoniae
0.079	-	ceftazidime	pH 7.2, 25°C, recombinant enzyme	Escherichia coli
0.082	-	Imipenem	pH 7.2, 25°C, recombinant enzyme	Escherichia coli
0.083	-	doripenem	pH 7.2, 25°C, recombinant enzyme	Escherichia coli
0.086	-	ceftazidime	pH 7.2, 25°C, recombinant enzyme	Escherichia coli
0.099	-	meropenem	pH 7.2, 25°C, recombinant enzyme	Escherichia coli
0.1	-	ceftazidime	pH 7.2, 25°C, recombinant enzyme	Klebsiella pneumoniae
0.107	-	cefoxitin	pH 7.2, 25°C, recombinant enzyme	Escherichia coli
0.11	-	ampicillin	pH 7.2, 25°C, recombinant enzyme	Klebsiella pneumoniae
0.115	-	ceftazidime	pH 7.2, 25°C, recombinant enzyme	Escherichia coli
0.119	-	meropenem	pH 7.2, 25°C, recombinant enzyme	Escherichia coli
0.119	-	doripenem	pH 7.2, 25°C, recombinant enzyme	Klebsiella pneumoniae
0.119	-	doripenem	pH 7.2, 25°C, recombinant enzyme	Escherichia coli
0.125	-	doripenem	pH 7.2, 25°C, recombinant enzyme	Escherichia coli
0.126	-	doripenem	pH 7.2, 25°C, recombinant enzyme	Escherichia coli
0.133	-	ceftazidime	pH 7.2, 25°C, recombinant enzyme	Escherichia coli
0.144	-	ceftazidime	pH 7.2, 25°C, recombinant enzyme	Escherichia coli
0.148	-	Imipenem	pH 7.2, 25°C, recombinant enzyme	Escherichia coli
0.151	-	doripenem	pH 7.2, 25°C, recombinant enzyme	Escherichia coli
0.156	-	ampicillin	pH 7.2, 25°C, recombinant enzyme	Escherichia coli
0.207	-	ampicillin	pH 7.2, 25°C, recombinant enzyme	Escherichia coli
0.229	-	ampicillin	pH 7.2, 25°C, recombinant enzyme	Escherichia coli
0.258	-	ampicillin	pH 7.2, 25°C, recombinant enzyme	Escherichia coli
0.305	-	ampicillin	pH 7.2, 25°C, recombinant enzyme	Escherichia coli
0.455	-	ampicillin	pH 7.2, 25°C, recombinant enzyme	Escherichia coli

Localization

Localization	Comment	Organism	GeneOntology No.	Textmining
periplasm	-	Klebsiella pneumoniae	-	-
periplasm	-	Acinetobacter baumannii	-	-
periplasm	-	Escherichia coli	-	-

Metals/Ions

Metals/Ions	Comment	Organism
Zn2+	a zinc metalloenzyme	Klebsiella pneumoniae
Zn2+	a zinc metalloenzyme	Acinetobacter baumannii
Zn2+	a zinc metalloenzyme	Escherichia coli

Organism

Organism	UniProt	Comment	Textmining
Acinetobacter baumannii	F2YZ26	gene blaNDM-2	-
Escherichia coli	A0A024FRL9	gene blaNDM-12	-
Escherichia coli	A0A0F6N6D4	gene blaNDM-5	-
Escherichia coli	H6WET3	gene blaNDM-6	-
Escherichia coli	H6WZS9	gene blaNDM-4	-
Escherichia coli	I3VKD5	gene blaNDM-3	-
Escherichia coli	J7I0S9	gene blaNDM-7	-
Escherichia coli	M1VE66	gene blaNDM-8	-
Klebsiella pneumoniae	C7C422	gene blaNDM-1	-
Klebsiella pneumoniae	S5ZIP8	gene blaNDM-10	-
Klebsiella pneumoniae	T2A6Y2	gene blaNDM-9	-

Purification (Commentary)

Purification (Comment)	Organism
recombinant N-terminally His6-tagged enzyme from Escherichia coli strain BL21(DE3) by nickel affinity chromatography, cleavage of the N-terminal His6-tag using recombinant human Rhinovirus 3C protease, and further purification of the untagged protein by affinity chromatography, followed by ultrafiltration	Klebsiella pneumoniae
recombinant N-terminally His6-tagged enzyme from Escherichia coli strain BL21(DE3) by nickel affinity chromatography, cleavage of the N-terminal His6-tag using recombinant human Rhinovirus 3C protease, and further purification of the untagged protein by affinity chromatography, followed by ultrafiltration	Acinetobacter baumannii
recombinant N-terminally His6-tagged enzyme from Escherichia coli strain BL21(DE3) by nickel affinity chromatography, cleavage of the N-terminal His6-tag using recombinant human Rhinovirus 3C protease, and further purification of the untagged protein by affinity chromatography, followed by ultrafiltration	Escherichia coli

Substrates and Products (Substrate)

Substrates	Comment Substrates	Organism	Products	Comment (Products)	Rev.
ampicillin + H2O	-	Klebsiella pneumoniae	(2R,4S)-2-[(R)-[[(2R)-2-amino-2-phenylacetyl]amino](carboxy)methyl]-5,5-dimethyl-1,3-thiazolidine-4-carboxylic acid	-	?
ampicillin + H2O	-	Acinetobacter baumannii	(2R,4S)-2-[(R)-[[(2R)-2-amino-2-phenylacetyl]amino](carboxy)methyl]-5,5-dimethyl-1,3-thiazolidine-4-carboxylic acid	-	?
ampicillin + H2O	-	Escherichia coli	(2R,4S)-2-[(R)-[[(2R)-2-amino-2-phenylacetyl]amino](carboxy)methyl]-5,5-dimethyl-1,3-thiazolidine-4-carboxylic acid	-	?
cefalotin + H2O	-	Klebsiella pneumoniae	(2R)-5-[(acetyloxy)methyl]-2-[(R)-carboxy[2-(thiophen-2-yl)acetamido]methyl]-3,6-dihydro-2H-1,3-thiazine-4-carboxylic acid	-	?
cefalotin + H2O	-	Escherichia coli	(2R)-5-[(acetyloxy)methyl]-2-[(R)-carboxy[2-(thiophen-2-yl)acetamido]methyl]-3,6-dihydro-2H-1,3-thiazine-4-carboxylic acid	-	?
cefoxitin + H2O	low activity	Klebsiella pneumoniae	(2R)-5-[(carbamoyloxy)methyl]-2-[(S)-carboxy(methoxy)[2-(thiophen-2-yl)acetamido]methyl]-3,6-dihydro-2H-1,3-thiazine-4-carboxylic acid	-	?
cefoxitin + H2O	low activity	Escherichia coli	(2R)-5-[(carbamoyloxy)methyl]-2-[(S)-carboxy(methoxy)[2-(thiophen-2-yl)acetamido]methyl]-3,6-dihydro-2H-1,3-thiazine-4-carboxylic acid	-	?
ceftazidime + H2O	low activity	Klebsiella pneumoniae	(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	-	?
ceftazidime + H2O	low activity	Escherichia coli	(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	-	?
doripenem + H2O	-	Klebsiella pneumoniae	(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	-	?
doripenem + H2O	-	Escherichia coli	(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	-	?
imipenem + H2O	-	Klebsiella pneumoniae	(5R)-5-[(1S,2R)-1-carboxy-2-hydroxypropyl]-3-([2-[(iminomethyl)amino]ethyl]sulfanyl)-4,5-dihydro-1H-pyrrole-2-carboxylic acid	-	?
imipenem + H2O	-	Escherichia coli	(5R)-5-[(1S,2R)-1-carboxy-2-hydroxypropyl]-3-([2-[(iminomethyl)amino]ethyl]sulfanyl)-4,5-dihydro-1H-pyrrole-2-carboxylic acid	-	?
meropenem + H2O	-	Klebsiella pneumoniae	(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	-	Escherichia coli	(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	-	Klebsiella pneumoniae	(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	-	?
nitrocefin + H2O	-	Escherichia coli	(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

Synonyms	Comment	Organism
MBL	-	Klebsiella pneumoniae
MBL	-	Acinetobacter baumannii
MBL	-	Escherichia coli
NDM	-	Klebsiella pneumoniae
NDM	-	Acinetobacter baumannii
NDM	-	Escherichia coli
NDM-1	-	Klebsiella pneumoniae
NDM-10	-	Klebsiella pneumoniae
NDM-12	-	Escherichia coli
NDM-2	-	Acinetobacter baumannii
NDM-3	-	Escherichia coli
NDM-4	-	Escherichia coli
NDM-5	-	Escherichia coli
NDM-6	-	Escherichia coli
NDM-7	-	Escherichia coli
NDM-8	-	Escherichia coli
NDM-9	-	Klebsiella pneumoniae
New Delhi MBL	-	Klebsiella pneumoniae
New Delhi MBL	-	Acinetobacter baumannii
New Delhi MBL	-	Escherichia coli
New Delhi metallo-beta-lactamase	-	Klebsiella pneumoniae
New Delhi metallo-beta-lactamase	-	Acinetobacter baumannii
New Delhi metallo-beta-lactamase	-	Escherichia coli

Temperature Optimum [°C]

Temperature Optimum [°C]	Temperature Optimum Maximum [°C]	Comment	Organism
25	-	assay at	Klebsiella pneumoniae
25	-	assay at	Acinetobacter baumannii
25	-	assay at	Escherichia coli

Temperature Stability [°C]

Temperature Stability Minimum [°C]	Temperature Stability Maximum [°C]	Comment	Organism
55.1	-	melting temperature of the purified NDM-1 variant	Escherichia coli
59.5	-	melting temperature of the purified NDM-1 variant	Klebsiella pneumoniae
61.4	-	melting temperature of the purified NDM-1 variant	Escherichia coli
63.4	-	melting temperature of the purified NDM-1 variant	Escherichia coli
64.6	-	melting temperature of the purified NDM-1 variant	Escherichia coli
72.1	-	melting temperature of the purified NDM-1 variant	Escherichia coli

Turnover Number [1/s]

Turnover Number Minimum [1/s]	Turnover Number Maximum [1/s]	Substrate	Comment	Organism
2	8	ceftazidime	pH 7.2, 25°C, recombinant enzyme	Escherichia coli
3	-	cefoxitin	pH 7.2, 25°C, recombinant enzyme	Escherichia coli
4	-	cefoxitin	pH 7.2, 25°C, recombinant enzyme	Escherichia coli
5	-	ceftazidime	pH 7.2, 25°C, recombinant enzyme	Escherichia coli
6	-	cefoxitin	pH 7.2, 25°C, recombinant enzyme	Escherichia coli
9	-	cefalotin	pH 7.2, 25°C, recombinant enzyme	Escherichia coli
10	-	cefoxitin	pH 7.2, 25°C, recombinant enzyme	Klebsiella pneumoniae
14	-	cefoxitin	pH 7.2, 25°C, recombinant enzyme	Escherichia coli
15	-	nitrocefin	pH 7.2, 25°C, recombinant enzyme	Escherichia coli
15	-	ceftazidime	pH 7.2, 25°C, recombinant enzyme	Escherichia coli
16	-	ceftazidime	pH 7.2, 25°C, recombinant enzyme	Escherichia coli
18	-	cefoxitin	pH 7.2, 25°C, recombinant enzyme	Escherichia coli
18	-	cefalotin	pH 7.2, 25°C, recombinant enzyme	Escherichia coli
23	-	ceftazidime	pH 7.2, 25°C, recombinant enzyme	Escherichia coli
24	-	ceftazidime	pH 7.2, 25°C, recombinant enzyme	Klebsiella pneumoniae
25	-	cefalotin	pH 7.2, 25°C, recombinant enzyme	Escherichia coli
29	-	ceftazidime	pH 7.2, 25°C, recombinant enzyme	Escherichia coli
30	-	nitrocefin	pH 7.2, 25°C, recombinant enzyme	Escherichia coli
33	-	nitrocefin	pH 7.2, 25°C, recombinant enzyme	Escherichia coli
38	-	nitrocefin	pH 7.2, 25°C, recombinant enzyme	Escherichia coli
44	-	nitrocefin	pH 7.2, 25°C, recombinant enzyme	Escherichia coli
45	-	cefalotin	pH 7.2, 25°C, recombinant enzyme	Escherichia coli
49	-	nitrocefin	pH 7.2, 25°C, recombinant enzyme	Escherichia coli
53	-	cefalotin	pH 7.2, 25°C, recombinant enzyme	Escherichia coli
54	-	Imipenem	pH 7.2, 25°C, recombinant enzyme	Escherichia coli
63	-	cefalotin	pH 7.2, 25°C, recombinant enzyme	Escherichia coli
65	-	nitrocefin	pH 7.2, 25°C, recombinant enzyme	Klebsiella pneumoniae
75	-	cefalotin	pH 7.2, 25°C, recombinant enzyme	Klebsiella pneumoniae
75	-	doripenem	pH 7.2, 25°C, recombinant enzyme	Escherichia coli
127	-	Imipenem	pH 7.2, 25°C, recombinant enzyme	Escherichia coli
142	-	meropenem	pH 7.2, 25°C, recombinant enzyme	Escherichia coli
170	-	doripenem	pH 7.2, 25°C, recombinant enzyme	Escherichia coli
194	-	meropenem	pH 7.2, 25°C, recombinant enzyme	Escherichia coli
226	-	doripenem	pH 7.2, 25°C, recombinant enzyme	Klebsiella pneumoniae
238	-	meropenem	pH 7.2, 25°C, recombinant enzyme	Escherichia coli
252	-	Imipenem	pH 7.2, 25°C, recombinant enzyme	Escherichia coli
267	-	doripenem	pH 7.2, 25°C, recombinant enzyme	Escherichia coli
273	-	ampicillin	pH 7.2, 25°C, recombinant enzyme	Escherichia coli
301	-	meropenem	pH 7.2, 25°C, recombinant enzyme	Klebsiella pneumoniae
332	-	Imipenem	pH 7.2, 25°C, recombinant enzyme	Escherichia coli
348	-	doripenem	pH 7.2, 25°C, recombinant enzyme	Escherichia coli
355	-	Imipenem	pH 7.2, 25°C, recombinant enzyme	Escherichia coli
362	-	meropenem	pH 7.2, 25°C, recombinant enzyme	Escherichia coli
408	-	ampicillin	pH 7.2, 25°C, recombinant enzyme	Escherichia coli
413	-	meropenem	pH 7.2, 25°C, recombinant enzyme	Escherichia coli
447	-	ampicillin	pH 7.2, 25°C, recombinant enzyme	Klebsiella pneumoniae
477	-	ampicillin	pH 7.2, 25°C, recombinant enzyme	Escherichia coli
583	-	meropenem	pH 7.2, 25°C, recombinant enzyme	Escherichia coli
600	-	Imipenem	pH 7.2, 25°C, recombinant enzyme	Klebsiella pneumoniae
724	-	ampicillin	pH 7.2, 25°C, recombinant enzyme	Escherichia coli
743	-	doripenem	pH 7.2, 25°C, recombinant enzyme	Escherichia coli
757	-	Imipenem	pH 7.2, 25°C, recombinant enzyme	Escherichia coli
900	-	ampicillin	pH 7.2, 25°C, recombinant enzyme	Escherichia coli
1032	-	doripenem	pH 7.2, 25°C, recombinant enzyme	Escherichia coli
1375	-	ampicillin	pH 7.2, 25°C, recombinant enzyme	Escherichia coli

pH Optimum

pH Optimum Minimum	pH Optimum Maximum	Comment	Organism
7.2	-	assay at	Klebsiella pneumoniae
7.2	-	assay at	Acinetobacter baumannii
7.2	-	assay at	Escherichia coli

Ki Value [mM]

Ki Value [mM]	Ki Value maximum [mM]	Inhibitor	Comment	Organism
0.079	-	nitrocefin	pH 7.2, 25°C, recombinant enzyme	Escherichia coli
0.102	-	nitrocefin	pH 7.2, 25°C, recombinant enzyme	Escherichia coli
0.139	-	nitrocefin	pH 7.2, 25°C, recombinant enzyme	Escherichia coli
0.146	-	nitrocefin	pH 7.2, 25°C, recombinant enzyme	Escherichia coli

General Information

General Information	Comment	Organism
additional information	different genotypes of the New Delhi metallo beta-lactamase are identified: the substitutions do not affect the overall folds of the enzyme variants, within limits of detection. Differences in thermal stabilities are observed. kcat/KM values are similar for carbapenem and penicillin substrates for NDM variants, but differences in kinetics are observed for cephalosporin substrates. Apparent substrate inhibition is observed with nitrocefin for variants containing the M154L substitution. In all cases, cefoxitin and ceftazidime are poorly hydrolysed. Clinically observed substitutions can make substantial differences in thermodynamic stability, suggesting that this may be a factor in metallo beta-lactamase evolution. Comparative analysis of the beta-lactam susceptibility of the NDM variants in Escherichia coli, overview	Klebsiella pneumoniae
additional information	different genotypes of the New Delhi metallo beta-lactamase are identified: the substitutions do not affect the overall folds of the enzyme variants, within limits of detection. Differences in thermal stabilities are observed. kcat/KM values are similar for carbapenem and penicillin substrates for NDM variants, but differences in kinetics are observed for cephalosporin substrates. Apparent substrate inhibition is observed with nitrocefin for variants containing the M154L substitution. In all cases, cefoxitin and ceftazidime are poorly hydrolysed. Clinically observed substitutions can make substantial differences in thermodynamic stability, suggesting that this may be a factor in metallo beta-lactamase evolution. Comparative analysis of the beta-lactam susceptibility of the NDM variants in Escherichia coli, overview	Acinetobacter baumannii
additional information	different genotypes of the New Delhi metallo beta-lactamase are identified: the substitutions do not affect the overall folds of the enzyme variants, within limits of detection. Differences in thermal stabilities are observed. kcat/KM values are similar for carbapenem and penicillin substrates for NDM variants, but differences in kinetics are observed for cephalosporin substrates. Apparent substrate inhibition is observed with nitrocefin for variants containing the M154L substitution. In all cases, cefoxitin and ceftazidime are poorly hydrolysed. Clinically observed substitutions can make substantial differences in thermodynamic stability, suggesting that this may be a factor in metallo beta-lactamase evolution. Comparative analysis of the beta-lactam susceptibility of the NDM variants in Escherichia coli, overview	Escherichia coli
additional information	different genotypes of the New Delhi metallo beta-lactamase are identified: the substitutions do not affect the overall folds of the enzyme variants, within limits of detection. Differences in thermal stabilities are observed. kcat/KM values are similar for carbapenem and penicillin substrates for NDM variants, but differences in kinetics are observed for cephalosporin substrates. Apparent substrate inhibition is observed with nitrocefin for variants containing the M154L substitution. In all cases, cefoxitin and ceftazidime are poorly hydrolysed. Clinically observed substitutions can make substantial differences in thermodynamic stability, suggesting that this may be a factor in metallo beta-lactamase evolution.Comparative analysis of the beta-lactam susceptibility of the NDM variants in Escherichia coli, overview	Escherichia coli
physiological function	New Delhi MBL (NDM)-1 is a clinically significant metallo beta-lactamase	Klebsiella pneumoniae

kcat/KM [mM/s]

kcat/KM Value [1/mMs^-1]	kcat/KM Value Maximum [1/mMs^-1]	Substrate	Comment	Organism
130	-	cefoxitin	pH 7.2, 25°C, recombinant enzyme	Escherichia coli
140	-	cefoxitin	pH 7.2, 25°C, recombinant enzyme	Escherichia coli
150	-	cefoxitin	pH 7.2, 25°C, recombinant enzyme	Escherichia coli
170	-	cefoxitin	pH 7.2, 25°C, recombinant enzyme	Escherichia coli
180	-	ceftazidime	pH 7.2, 25°C, recombinant enzyme	Escherichia coli
180	-	cefoxitin	pH 7.2, 25°C, recombinant enzyme	Escherichia coli
200	-	ceftazidime	pH 7.2, 25°C, recombinant enzyme	Escherichia coli
210	-	ceftazidime	pH 7.2, 25°C, recombinant enzyme	Escherichia coli
220	-	cefoxitin	pH 7.2, 25°C, recombinant enzyme	Escherichia coli
230	-	ceftazidime	pH 7.2, 25°C, recombinant enzyme	Klebsiella pneumoniae
230	-	cefoxitin	pH 7.2, 25°C, recombinant enzyme	Klebsiella pneumoniae
260	-	ceftazidime	pH 7.2, 25°C, recombinant enzyme	Escherichia coli
1200	-	ampicillin	pH 7.2, 25°C, recombinant enzyme	Escherichia coli
1500	-	cefalotin	pH 7.2, 25°C, recombinant enzyme	Escherichia coli
1600	-	cefalotin	pH 7.2, 25°C, recombinant enzyme	Escherichia coli
1700	-	doripenem	pH 7.2, 25°C, recombinant enzyme	Escherichia coli
1900	-	cefalotin	pH 7.2, 25°C, recombinant enzyme	Escherichia coli
1900	-	doripenem	pH 7.2, 25°C, recombinant enzyme	Klebsiella pneumoniae
2000	-	doripenem	pH 7.2, 25°C, recombinant enzyme	Escherichia coli
2200	-	Imipenem	pH 7.2, 25°C, recombinant enzyme	Escherichia coli
2300	-	ampicillin	pH 7.2, 25°C, recombinant enzyme	Escherichia coli
2300	-	Imipenem	pH 7.2, 25°C, recombinant enzyme	Escherichia coli
2600	-	ampicillin	pH 7.2, 25°C, recombinant enzyme	Escherichia coli
2600	-	meropenem	pH 7.2, 25°C, recombinant enzyme	Escherichia coli
2600	-	cefalotin	pH 7.2, 25°C, recombinant enzyme	Klebsiella pneumoniae
2800	-	ampicillin	pH 7.2, 25°C, recombinant enzyme	Escherichia coli
2900	-	ampicillin	pH 7.2, 25°C, recombinant enzyme	Escherichia coli
2900	-	Imipenem	pH 7.2, 25°C, recombinant enzyme	Escherichia coli
3000	-	ampicillin	pH 7.2, 25°C, recombinant enzyme	Escherichia coli
3100	-	nitrocefin	pH 7.2, 25°C, recombinant enzyme	Escherichia coli
4100	-	ampicillin	pH 7.2, 25°C, recombinant enzyme	Klebsiella pneumoniae
4100	-	Imipenem	pH 7.2, 25°C, recombinant enzyme	Escherichia coli
4100	-	meropenem	pH 7.2, 25°C, recombinant enzyme	Escherichia coli
4100	-	cefalotin	pH 7.2, 25°C, recombinant enzyme	Escherichia coli
4200	-	meropenem	pH 7.2, 25°C, recombinant enzyme	Escherichia coli
4300	-	meropenem	pH 7.2, 25°C, recombinant enzyme	Escherichia coli
4500	-	doripenem	pH 7.2, 25°C, recombinant enzyme	Escherichia coli
4600	-	cefalotin	pH 7.2, 25°C, recombinant enzyme	Escherichia coli
4900	-	meropenem	pH 7.2, 25°C, recombinant enzyme	Escherichia coli
5200	-	meropenem	pH 7.2, 25°C, recombinant enzyme	Klebsiella pneumoniae
5400	-	doripenem	pH 7.2, 25°C, recombinant enzyme	Escherichia coli
5600	-	nitrocefin	pH 7.2, 25°C, recombinant enzyme	Escherichia coli
5800	-	Imipenem	pH 7.2, 25°C, recombinant enzyme	Escherichia coli
5900	-	nitrocefin	pH 7.2, 25°C, recombinant enzyme	Klebsiella pneumoniae
6000	-	doripenem	pH 7.2, 25°C, recombinant enzyme	Escherichia coli
6100	-	nitrocefin	pH 7.2, 25°C, recombinant enzyme	Escherichia coli
6100	-	cefalotin	pH 7.2, 25°C, recombinant enzyme	Escherichia coli
6300	-	nitrocefin	pH 7.2, 25°C, recombinant enzyme	Escherichia coli
7400	-	meropenem	pH 7.2, 25°C, recombinant enzyme	Escherichia coli
7500	-	nitrocefin	pH 7.2, 25°C, recombinant enzyme	Escherichia coli
7600	-	Imipenem	pH 7.2, 25°C, recombinant enzyme	Klebsiella pneumoniae
8600	-	doripenem	pH 7.2, 25°C, recombinant enzyme	Escherichia coli
9200	-	Imipenem	pH 7.2, 25°C, recombinant enzyme	Escherichia coli
10900	-	nitrocefin	pH 7.2, 25°C, recombinant enzyme	Escherichia coli