C7C422 (BLAN1_KLEPN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Beta-lactamase NDM-1
Short name=NDM-1
EC=3.5.2.6

Alternative name(s):
Metallo-beta-lactamase NDM-1

Gene names

Name:

blaNDM-1

Encoded on

Plasmid pKpANDM-1

Organism

Klebsiella pneumoniae

Taxonomic identifier

573 [NCBI]

Taxonomic lineage

cellular organisms › Bacteria › Proteobacteria › Gammaproteobacteria › Enterobacteriales › Enterobacteriaceae › Klebsiella

Protein attributes

Sequence length	270 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is further processed into a mature form.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	Confers resistance to many beta-lactam antibiotics, including some carbapenems. Does not confer resistance to the polymixin colistin or the fluoroquinolone ciprofloxacin. Ref.1
Catalytic activity	A beta-lactam + H2O = a substituted beta-amino acid. Ref.1
Cofactor	Binds 2 zinc ions per subunit By similarity.
Subunit structure	Monomer. Ref.1
Subcellular location	Periplasm Potential. Note: The predicted signal sequence is not very convincing.
Miscellaneous	Enterobacteriaceae carrying this gene (identified by PCR) have been isolated in Sweden, India, Pakistan, Bangladesh, England, Scotland, Northern Ireland, Australia and the USA. The organisms they were identified in were K.pneumoniae, Enterobacter cloacae, E.coli, Proteus spp, Citrobacter freundii, Morganella morganii, Providencia spp and Klebsille oxytoca. In India most isolates were from community-acquired infections rather than hospital-acquired infections, indicating the gene is widespread in the environment.
Sequence similarities	Belongs to the class-B beta-lactamase family.
Caution	Transfer of a plasmid encoding this gene has been detected between bacteria within a patient (between K.pneumoniae and E.coli). Additionally the gene may be encoded within a transposon.
Biophysicochemical properties	Kinetic parameters: No activity detected against the monobactam aztreonam or the beta-lactamase inhibitor clavulanic acid. KM=8 µM for cefuroxime Ref.1 KM=10 µM for cefotaxime KM=10 µM for cephalothin KM=12 µM for piperacillin KM=16 µM for penicillin G KM=22 µM for ampicillin KM=49 µM for cefoxitin KM=49 µM for meropenem KM=77 µM for cefepime KM=94 µM for imipenem KM=181 µM for ceftazidime

Ontologies

Keywords
Biological process	Antibiotic resistance
Cellular component	Periplasm
Domain	Signal
Ligand	Metal-binding Zinc
Molecular function	Hydrolase
Technical term	3D-structure Plasmid
Gene Ontology (GO)
Biological_process	response to antibiotic Inferred from electronic annotation. Source: UniProtKB-KW
Cellular_component	periplasmic space Inferred from electronic annotation. Source: UniProtKB-SubCell
Molecular_function	beta-lactamase activity Inferred from electronic annotation. Source: EC metal ion binding Inferred from electronic annotation. Source: UniProtKB-KW
Complete GO annotation...

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Signal peptide

1 – 28

28

Potential

Chain

29 – 270

242

Beta-lactamase NDM-1

PRO_0000400316

Sites

Metal binding

120

1

Zinc 1 By similarity

Metal binding

122

1

Zinc 1 By similarity

Metal binding

124

1

Zinc 2 By similarity

Metal binding

189

1

Zinc 1 By similarity

Metal binding

208

1

Zinc 2 By similarity

Metal binding

250

1

Zinc 2 By similarity

Secondary structure

1

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270

Helix Strand Turn

Details...

Beta strand

34 – 36

3

Beta strand

43 – 46

4

Beta strand

49 – 55

7

Beta strand

58 – 67

10

Turn

68 – 70

3

Beta strand

71 – 82

12

Beta strand

85 – 90

6

Helix

95 – 108

14

Beta strand

113 – 117

5

Beta strand

120 – 122

3

Helix

123 – 126

4

Helix

129 – 134

6

Beta strand

138 – 142

5

Helix

143 – 148

6

Helix

149 – 151

3

Beta strand

158 – 161

4

Beta strand

167 – 169

3

Helix

171 – 173

3

Beta strand

180 – 183

4

Beta strand

187 – 190

4

Beta strand

195 – 198

4

Turn

199 – 202

4

Beta strand

203 – 205

3

Turn

207 – 209

3

Helix

221 – 223

3

Turn

226 – 228

3

Helix

229 – 239

11

Beta strand

245 – 247

3

Beta strand

249 – 251

3

Helix

257 – 267

11

Sequences

	Sequence		Length	Mass (Da)
	C7C422 [UniParc]. Last modified September 22, 2009. Version 1. Checksum: 1B6009120B945F14	FASTA	270	28,499
	10 20 30 40 50 60 MELPNIMHPV AKLSTALAAA LMLSGCMPGE IRPTIGQQME TGDQRFGDLV FRQLAPNVWQ 70 80 90 100 110 120 HTSYLDMPGF GAVASNGLIV RDGGRVLVVD TAWTDDQTAQ ILNWIKQEIN LPVALAVVTH 130 140 150 160 170 180 AHQDKMGGMD ALHAAGIATY ANALSNQLAP QEGMVAAQHS LTFAANGWVE PATAPNFGPL 190 200 210 220 230 240 KVFYPGPGHT SDNITVGIDG TDIAFGGCLI KDSKAKSLGN LGDADTEHYA ASARAFGAAF 250 260 270 PKASMIVMSH SAPDSRAAIT HTARMADKLR

References

[1]	"Characterization of a new metallo-beta-lactamase gene, bla(NDM-1), and a novel erythromycin esterase gene carried on a unique genetic structure in Klebsiella pneumoniae sequence type 14 from India." Yong D., Toleman M.A., Giske C.G., Cho H.S., Sundman K., Lee K., Walsh T.R. Antimicrob. Agents Chemother. 53:5046-5054(2009) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], FUNCTION, CATALYTIC ACTIVITY, SUBUNIT, BIOPHYSICOCHEMICAL PROPERTIES. Strain: KP-05-506.
[2]	"Emergence of a new antibiotic resistance mechanism in India, Pakistan, and the UK: a molecular, biological, and epidemiological study." Kumarasamy K.K., Toleman M.A., Walsh T.R., Bagaria J., Butt F., Balakrishnan R., Chaudhary U., Doumith M., Giske C.G., Irfan S., Krishnan P., Kumar A.V., Maharjan S., Mushtaq S., Noorie T., Paterson D.L., Pearson A., Perry C. , Pike R., Rao B., Ray U., Sarma J.B., Sharma M., Sheridan E., Thirunarayan M.A., Turton J., Upadhyay S., Warner M., Welfare W., Livermore D.M., Woodford N. Lancet Infect. Dis. 10:597-602(2010) [PubMed] [Europe PMC] [Abstract] Cited for: EPIDEMIOLOGY.
[3]	"Detection of Enterobacteriaceae isolates carrying metallo-beta-lactamase -United States, 2010." Limbago B., Kallen A. MMWR Morb. Mortal. Wkly. Rep. 59:750-750(2010) [PubMed] [Europe PMC] [Abstract] Cited for: EPIDEMIOLOGY.
+	Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

FN396876 Genomic DNA. Translation: CAZ39946.1.

RefSeq

YP_005352173.1. NC_016980.1.
YP_006958736.1. NC_019153.1.
YP_006959150.1. NC_019158.1.
YP_006959255.1. NC_019162.1.
YP_006959318.1. NC_019163.1.
YP_006959370.1. NC_019164.1.
YP_007195502.1. NC_019889.1.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
3PG4	X-ray	2.00	A	49-270	[»]
3Q6X	X-ray	1.30	A/B	29-270	[»]
3RKJ	X-ray	2.00	A/B	39-270	[»]
3RKK	X-ray	2.35	A/B	39-270	[»]
3SBL	X-ray	2.31	A	39-270	[»]
3SFP	X-ray	2.27	A/B/C/D	39-270	[»]
3SPU	X-ray	2.10	A/B/C/D/E	27-270	[»]
3SRX	X-ray	2.50	A/B	39-270	[»]
3ZR9	X-ray	1.91	A	42-270	[»]
4EXS	X-ray	2.40	A/B	1-270	[»]
4EXY	X-ray	1.47	A/B	1-270	[»]
4EY2	X-ray	1.17	A/B	1-270	[»]
4EYB	X-ray	1.16	A/B	1-270	[»]
4EYF	X-ray	1.80	A/B	1-270	[»]
4EYL	X-ray	1.90	A/B	1-270	[»]
4GYQ	X-ray	1.35	A/B/C/D	31-270	[»]
4GYU	X-ray	1.80	A	31-270	[»]
4H0D	X-ray	1.50	A/B	31-270	[»]
4HKY	X-ray	2.00	A/B	31-270	[»]
4HL1	X-ray	1.50	A/B	31-270	[»]
4HL2	X-ray	1.05	A/B	31-270	[»]

ProteinModelPortal

C7C422.

ModBase

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Protocols and materials databases

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

GeneID

11934636.
13913959.
13914060.
13914125.
13914179.
13914405.
14258327.

Family and domain databases

InterPro

IPR001279. Beta-lactamas-like.
[Graphical view]

Pfam

PF00753. Lactamase_B. 1 hit.
[Graphical view]

SMART

SM00849. Lactamase_B. 1 hit.
[Graphical view]

PROSITE

PS00743. BETA_LACTAMASE_B_1. False negative.
PS00744. BETA_LACTAMASE_B_2. False negative.
[Graphical view]

ProtoNet

Search...

Other

ChEMBL

CHEMBL1667695.

EvolutionaryTrace

C7C422.

Entry information

Entry name

BLAN1_KLEPN

Accession

Primary (citable) accession number: C7C422

Entry history

Integrated into UniProtKB/Swiss-Prot:	November 2, 2010
Last sequence update:	September 22, 2009
Last modified:	April 3, 2013
This is version 22 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Prokaryotic Protein Annotation Program