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Protein

Beta-lactamase NDM-1

Gene

blaNDM-1

Organism
Klebsiella pneumoniae
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

Confers resistance to many beta-lactam antibiotics, including some carbapenems. Does not confer resistance to the polymixin colistin or the fluoroquinolone ciprofloxacin.1 Publication

Catalytic activityi

A beta-lactam + H2O = a substituted beta-amino acid.1 Publication

Cofactori

Zn2+By similarityNote: Binds 2 Zn2+ ions per subunit.By similarity

Kineticsi

No activity detected against the monobactam aztreonam or the beta-lactamase inhibitor clavulanic acid.

  1. KM=8 µM for cefuroxime1 Publication
  2. KM=10 µM for cefotaxime1 Publication
  3. KM=10 µM for cephalothin1 Publication
  4. KM=12 µM for piperacillin1 Publication
  5. KM=16 µM for penicillin G1 Publication
  6. KM=22 µM for ampicillin1 Publication
  7. KM=49 µM for cefoxitin1 Publication
  8. KM=49 µM for meropenem1 Publication
  9. KM=77 µM for cefepime1 Publication
  10. KM=94 µM for imipenem1 Publication
  11. KM=181 µM for ceftazidime1 Publication

    Sites

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Metal bindingi120 – 1201Zinc 1By similarity
    Metal bindingi122 – 1221Zinc 1By similarity
    Metal bindingi124 – 1241Zinc 2By similarity
    Metal bindingi189 – 1891Zinc 1By similarity
    Metal bindingi208 – 2081Zinc 2By similarity
    Metal bindingi250 – 2501Zinc 2By similarity

    GO - Molecular functioni

    GO - Biological processi

    Complete GO annotation...

    Keywords - Molecular functioni

    Hydrolase

    Keywords - Biological processi

    Antibiotic resistance

    Keywords - Ligandi

    Metal-binding, Zinc

    Names & Taxonomyi

    Protein namesi
    Recommended name:
    Beta-lactamase NDM-1 (EC:3.5.2.6)
    Short name:
    NDM-1
    Alternative name(s):
    Metallo-beta-lactamase NDM-1
    Gene namesi
    Name:blaNDM-1
    Encoded oniPlasmid pKpANDM-10 Publication
    OrganismiKlebsiella pneumoniae
    Taxonomic identifieri573 [NCBI]
    Taxonomic lineageiBacteriaProteobacteriaGammaproteobacteriaEnterobacterialesEnterobacteriaceaeKlebsiella

    Subcellular locationi

    • Periplasm Curated

    • Note: The predicted signal sequence is not very convincing.

    GO - Cellular componenti

    Complete GO annotation...

    Keywords - Cellular componenti

    Periplasm

    PTM / Processingi

    Molecule processing

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Signal peptidei1 – 2828Sequence AnalysisAdd
    BLAST
    Chaini29 – 270242Beta-lactamase NDM-1PRO_0000400316Add
    BLAST

    Interactioni

    Subunit structurei

    Monomer.1 Publication

    Structurei

    Secondary structure

    1
    270
    Legend: HelixTurnBeta strand
    Show more details
    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Beta strandi34 – 363Combined sources
    Beta strandi43 – 464Combined sources
    Beta strandi49 – 557Combined sources
    Beta strandi58 – 6710Combined sources
    Turni68 – 703Combined sources
    Beta strandi71 – 8212Combined sources
    Beta strandi85 – 906Combined sources
    Helixi95 – 10814Combined sources
    Beta strandi113 – 1175Combined sources
    Beta strandi120 – 1223Combined sources
    Helixi123 – 1264Combined sources
    Helixi129 – 1346Combined sources
    Beta strandi138 – 1425Combined sources
    Helixi143 – 1486Combined sources
    Helixi149 – 1513Combined sources
    Beta strandi158 – 1614Combined sources
    Beta strandi167 – 1693Combined sources
    Helixi171 – 1733Combined sources
    Beta strandi180 – 1834Combined sources
    Beta strandi187 – 1904Combined sources
    Beta strandi195 – 1984Combined sources
    Turni199 – 2024Combined sources
    Beta strandi203 – 2053Combined sources
    Turni207 – 2093Combined sources
    Helixi221 – 2233Combined sources
    Turni226 – 2283Combined sources
    Helixi229 – 23911Combined sources
    Beta strandi245 – 2473Combined sources
    Beta strandi249 – 2513Combined sources
    Helixi257 – 26711Combined sources

    3D structure databases

    Select the link destinations:
    PDBei
    RCSB PDBi
    PDBji
    Links Updated
    EntryMethodResolution (Å)ChainPositionsPDBsum
    3PG4X-ray2.00A49-270[»]
    3Q6XX-ray1.30A/B29-270[»]
    3RKJX-ray2.00A/B39-270[»]
    3RKKX-ray2.35A/B39-270[»]
    3SBLX-ray2.31A39-270[»]
    3SFPX-ray2.27A/B/C/D39-270[»]
    3SPUX-ray2.10A/B/C/D/E27-270[»]
    3SRXX-ray2.50A/B37-270[»]
    3ZR9X-ray1.91A42-270[»]
    4EXSX-ray2.40A/B1-270[»]
    4EXYX-ray1.47A/B1-270[»]
    4EY2X-ray1.17A/B1-270[»]
    4EYBX-ray1.16A/B1-270[»]
    4EYFX-ray1.80A/B1-270[»]
    4EYLX-ray1.90A/B1-270[»]
    4GYQX-ray1.35A/B/C/D31-270[»]
    4GYUX-ray1.80A31-270[»]
    4H0DX-ray1.50A/B31-270[»]
    4HKYX-ray2.00A/B31-270[»]
    4HL1X-ray1.50A/B31-270[»]
    4HL2X-ray1.05A/B31-270[»]
    4RAMX-ray1.50A/B31-270[»]
    4RAWX-ray1.30A/B31-270[»]
    4RBSX-ray2.40A/B31-270[»]
    4RL0X-ray1.30A/B29-270[»]
    4RL2X-ray2.01A/B29-270[»]
    4RM5X-ray2.10A/B/C/D29-270[»]
    4U4LX-ray1.90A/B/C/D27-270[»]
    ProteinModelPortaliC7C422.
    ModBaseiSearch...
    MobiDBiSearch...

    Miscellaneous databases

    EvolutionaryTraceiC7C422.

    Family & Domainsi

    Sequence similaritiesi

    Keywords - Domaini

    Signal

    Phylogenomic databases

    KOiK18780.

    Family and domain databases

    Gene3Di3.60.15.10. 1 hit.
    InterProiIPR001279. Beta-lactamas-like.
    [Graphical view]
    PfamiPF00753. Lactamase_B. 1 hit.
    [Graphical view]
    SMARTiSM00849. Lactamase_B. 1 hit.
    [Graphical view]
    SUPFAMiSSF56281. SSF56281. 1 hit.

    Sequencei

    Sequence statusi: Complete.

    Sequence processingi: The displayed sequence is further processed into a mature form.

    C7C422-1 [UniParc]FASTAAdd to basket

    « Hide

            10         20         30         40         50
    MELPNIMHPV AKLSTALAAA LMLSGCMPGE IRPTIGQQME TGDQRFGDLV
    60 70 80 90 100
    FRQLAPNVWQ HTSYLDMPGF GAVASNGLIV RDGGRVLVVD TAWTDDQTAQ
    110 120 130 140 150
    ILNWIKQEIN LPVALAVVTH AHQDKMGGMD ALHAAGIATY ANALSNQLAP
    160 170 180 190 200
    QEGMVAAQHS LTFAANGWVE PATAPNFGPL KVFYPGPGHT SDNITVGIDG
    210 220 230 240 250
    TDIAFGGCLI KDSKAKSLGN LGDADTEHYA ASARAFGAAF PKASMIVMSH
    260 270
    SAPDSRAAIT HTARMADKLR
    Length:270
    Mass (Da):28,499
    Last modified:September 22, 2009 - v1
    Checksum:i1B6009120B945F14
    GO

    Sequence databases

    Select the link destinations:
    EMBLi
    GenBanki
    DDBJi
    Links Updated
    FN396876 Genomic DNA. Translation: CAZ39946.1.
    RefSeqiWP_004201164.1. NZ_LAFX01000011.1.
    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_007195502.1. NC_019889.1.
    YP_007641427.1. NC_020811.1.
    YP_007936899.1. NC_021180.1.
    YP_008719663.1. NC_022609.1.
    YP_009023060.1. NC_023908.1.
    YP_009066437.1. NC_025105.1.
    YP_009071638.1. NC_025184.1.
    YP_009082638.1. NG_036789.1.
    YP_009083148.1. NG_036912.1.
    YP_009089162.1. NG_041250.1.
    YP_009090736.1. NG_041628.1.
    YP_009090740.1. NG_041629.1.
    YP_009090902.1. NG_041664.1.
    YP_009091191.1. NG_041672.1.

    Genome annotation databases

    GeneIDi11934636.
    13913959.
    13914060.
    13914125.
    13914405.
    14258327.
    14858116.
    15407950.
    17373266.
    18983573.
    20471925.
    20494087.
    KEGGipg:11934636.
    pg:13913959.
    pg:13914060.
    pg:13914125.
    pg:13914405.
    pg:14258327.
    pg:14858116.
    pg:15407950.
    pg:17373266.
    pg:18983573.
    pg:20471925.
    pg:20494087.

    Cross-referencesi

    Sequence databases

    Select the link destinations:
    EMBLi
    GenBanki
    DDBJi
    Links Updated
    FN396876 Genomic DNA. Translation: CAZ39946.1.
    RefSeqiWP_004201164.1. NZ_LAFX01000011.1.
    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_007195502.1. NC_019889.1.
    YP_007641427.1. NC_020811.1.
    YP_007936899.1. NC_021180.1.
    YP_008719663.1. NC_022609.1.
    YP_009023060.1. NC_023908.1.
    YP_009066437.1. NC_025105.1.
    YP_009071638.1. NC_025184.1.
    YP_009082638.1. NG_036789.1.
    YP_009083148.1. NG_036912.1.
    YP_009089162.1. NG_041250.1.
    YP_009090736.1. NG_041628.1.
    YP_009090740.1. NG_041629.1.
    YP_009090902.1. NG_041664.1.
    YP_009091191.1. NG_041672.1.

    3D structure databases

    Select the link destinations:
    PDBei
    RCSB PDBi
    PDBji
    Links Updated
    EntryMethodResolution (Å)ChainPositionsPDBsum
    3PG4X-ray2.00A49-270[»]
    3Q6XX-ray1.30A/B29-270[»]
    3RKJX-ray2.00A/B39-270[»]
    3RKKX-ray2.35A/B39-270[»]
    3SBLX-ray2.31A39-270[»]
    3SFPX-ray2.27A/B/C/D39-270[»]
    3SPUX-ray2.10A/B/C/D/E27-270[»]
    3SRXX-ray2.50A/B37-270[»]
    3ZR9X-ray1.91A42-270[»]
    4EXSX-ray2.40A/B1-270[»]
    4EXYX-ray1.47A/B1-270[»]
    4EY2X-ray1.17A/B1-270[»]
    4EYBX-ray1.16A/B1-270[»]
    4EYFX-ray1.80A/B1-270[»]
    4EYLX-ray1.90A/B1-270[»]
    4GYQX-ray1.35A/B/C/D31-270[»]
    4GYUX-ray1.80A31-270[»]
    4H0DX-ray1.50A/B31-270[»]
    4HKYX-ray2.00A/B31-270[»]
    4HL1X-ray1.50A/B31-270[»]
    4HL2X-ray1.05A/B31-270[»]
    4RAMX-ray1.50A/B31-270[»]
    4RAWX-ray1.30A/B31-270[»]
    4RBSX-ray2.40A/B31-270[»]
    4RL0X-ray1.30A/B29-270[»]
    4RL2X-ray2.01A/B29-270[»]
    4RM5X-ray2.10A/B/C/D29-270[»]
    4U4LX-ray1.90A/B/C/D27-270[»]
    ProteinModelPortaliC7C422.
    ModBaseiSearch...
    MobiDBiSearch...

    Chemistry

    ChEMBLiCHEMBL1667695.

    Protocols and materials databases

    Structural Biology KnowledgebaseSearch...

    Genome annotation databases

    GeneIDi11934636.
    13913959.
    13914060.
    13914125.
    13914405.
    14258327.
    14858116.
    15407950.
    17373266.
    18983573.
    20471925.
    20494087.
    KEGGipg:11934636.
    pg:13913959.
    pg:13914060.
    pg:13914125.
    pg:13914405.
    pg:14258327.
    pg:14858116.
    pg:15407950.
    pg:17373266.
    pg:18983573.
    pg:20471925.
    pg:20494087.

    Phylogenomic databases

    KOiK18780.

    Miscellaneous databases

    EvolutionaryTraceiC7C422.
    PROiC7C422.

    Family and domain databases

    Gene3Di3.60.15.10. 1 hit.
    InterProiIPR001279. Beta-lactamas-like.
    [Graphical view]
    PfamiPF00753. Lactamase_B. 1 hit.
    [Graphical view]
    SMARTiSM00849. Lactamase_B. 1 hit.
    [Graphical view]
    SUPFAMiSSF56281. SSF56281. 1 hit.
    ProtoNetiSearch...

    Publicationsi

    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. 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.

    Entry informationi

    Entry nameiBLAN1_KLEPN
    AccessioniPrimary (citable) accession number: C7C422
    Entry historyi
    Integrated into UniProtKB/Swiss-Prot: November 2, 2010
    Last sequence update: September 22, 2009
    Last modified: July 22, 2015
    This is version 41 of the entry and version 1 of the sequence. [Complete history]
    Entry statusiReviewed (UniProtKB/Swiss-Prot)
    Annotation programProkaryotic Protein Annotation Program

    Miscellaneousi

    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.

    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.Curated

    Keywords - Technical termi

    3D-structure, Plasmid

    Documents

    1. PDB cross-references
      Index of Protein Data Bank (PDB) cross-references
    2. SIMILARITY comments
      Index of protein domains and families

    External Data

    Dasty 3

    Similar proteinsi

    Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
    100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into Uniref entry.
    90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
    50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.