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O53223

- LDT2_MYCTO

UniProt

O53223 - LDT2_MYCTO

Protein

L,D-transpeptidase 2

Gene

ldtB

Organism
Mycobacterium tuberculosis (strain CDC 1551 / Oshkosh)
Status
Reviewed - Annotation score: 5 out of 5- Experimental evidence at protein leveli
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    • History
      Entry version 84 (01 Oct 2014)
      Sequence version 1 (01 Jun 1998)
      Previous versions | rss
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    Functioni

    Generates 3->3 cross-links in peptidoglycan, catalyzing the cleavage of the mDap(3)-D-Ala4 bond of a tetrapeptide donor stem and the formation of a bond between the carbonyl of mDap3 of the donor stem and the side chain of mDap3 of the acceptor stem. Is specific for donor substrates containing a stem tetrapeptide since it cannot use pentapeptide stems. Is essential for virulence in a mouse model of acute infection.1 Publication

    Enzyme regulationi

    Is irreversibly inactivated by the beta-lactams carbapenems via the formation of a covalent adduct resulting from acylation of the catalytic Cys.By similarity

    Pathwayi

    Sites

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Metal bindingi232 – 2321CalciumBy similarity
    Metal bindingi235 – 2351Calcium; via amide nitrogenBy similarity
    Metal bindingi236 – 2361Calcium; via amide nitrogenBy similarity
    Binding sitei318 – 3181Substrate
    Active sitei336 – 3361Proton donor/acceptor1 Publication
    Active sitei354 – 3541Nucleophile1 Publication
    Sitei354 – 3541Binds to carbapenem drug (covalent)By similarity
    Binding sitei356 – 3561Substrate

    GO - Molecular functioni

    1. metal ion binding Source: UniProtKB-KW
    2. peptidoglycan L,D-transpeptidase activity Source: MTBBASE
    3. transferase activity Source: InterPro

    GO - Biological processi

    1. peptidoglycan-based cell wall biogenesis Source: MTBBASE
    2. peptidoglycan metabolic process Source: MTBBASE
    3. proteolysis Source: GOC

    Keywords - Molecular functioni

    Acyltransferase, Transferase

    Keywords - Biological processi

    Cell shape, Cell wall biogenesis/degradation, Peptidoglycan synthesis, Virulence

    Keywords - Ligandi

    Calcium, Metal-binding

    Enzyme and pathway databases

    BioCyciMTBRV:RV2518C-MONOMER.
    UniPathwayiUPA00219.

    Names & Taxonomyi

    Protein namesi
    Recommended name:
    L,D-transpeptidase 2 (EC:2.3.2.-)
    Short name:
    LDT 2
    Alternative name(s):
    Ldt(Mt2)
    Gene namesi
    Name:ldtB
    Ordered Locus Names:MT2594
    ORF Names:V735_02606
    OrganismiMycobacterium tuberculosis (strain CDC 1551 / Oshkosh)
    Taxonomic identifieri83331 [NCBI]
    Taxonomic lineageiBacteriaActinobacteriaActinobacteridaeActinomycetalesCorynebacterineaeMycobacteriaceaeMycobacteriumMycobacterium tuberculosis complex
    ProteomesiUP000001020: Chromosome

    Subcellular locationi

    Cell membrane PROSITE-ProRule annotation; Lipid-anchor PROSITE-ProRule annotation

    GO - Cellular componenti

    1. cell wall Source: MTBBASE

    Keywords - Cellular componenti

    Cell membrane, Membrane

    Pathology & Biotechi

    Disruption phenotypei

    Inactivation of this gene leads to altered colony morphology and growth, attenuation of persistence and increased susceptibility to amoxicillin-clavulanate both in vitro and in the mouse model during the chronic phase of infection. Loss of both ldtMt1 and ldtMt2 results in phenotypes that are unique and/or severe compared to the single mutants lacking only ldtMt1 or ldtMt2. The double gene deletion severely alters cellular shape, intracellular morphology, physiology and virulence: the length of mutant cells are shorter than wild-type, they have deep surface depressions and bulges, they possess large unstained vacuole-like structures, the thickness of the peptidoglycan layer is smaller, the protein localization is altered, and in vitro and in vivo growth and virulence are severly attenuated. Moreover, double-mutant cells are more sensitive to vancomycin and amoxicillin-clavulanate.2 Publications

    PTM / Processingi

    Molecule processing

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Signal peptidei1 – 3434PROSITE-ProRule annotationAdd
    BLAST
    Chaini35 – 408374L,D-transpeptidase 2PRO_0000430333Add
    BLAST

    Amino acid modifications

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Lipidationi35 – 351N-palmitoyl cysteinePROSITE-ProRule annotation
    Lipidationi35 – 351S-diacylglycerol cysteinePROSITE-ProRule annotation

    Keywords - PTMi

    Lipoprotein, Palmitate

    Expressioni

    Inductioni

    Is expressed at a level higher than other LDT paralogs at all phases of growth.1 Publication

    Interactioni

    Subunit structurei

    Monomer.1 Publication

    Protein-protein interaction databases

    STRINGi83332.Rv2518c.

    Structurei

    3D structure databases

    Select the link destinations:
    PDBe
    RCSB PDB
    PDBj
    Links Updated
    EntryMethodResolution (Å)ChainPositionsPDBsum
    3TURX-ray1.72A/B122-408[»]
    3TX4X-ray2.32A/B122-408[»]
    3U1PX-ray2.80A/B122-408[»]
    3U1QX-ray2.40A/B122-408[»]
    3VAEX-ray2.80A/B122-408[»]
    ProteinModelPortaliO53223.
    SMRiO53223. Positions 58-406.
    ModBaseiSearch...
    MobiDBiSearch...

    Family & Domainsi

    Domains and Repeats

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Domaini259 – 377119YkuDAdd
    BLAST

    Region

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Regioni331 – 3322Substrate binding

    Sequence similaritiesi

    Contains 1 YkuD domain.Curated

    Keywords - Domaini

    Signal

    Phylogenomic databases

    HOGENOMiHOG000241380.
    OMAiNAEWFYD.
    OrthoDBiEOG66QKTJ.

    Family and domain databases

    InterProiIPR005490. LD_TPept_cat_dom.
    [Graphical view]
    PfamiPF03734. YkuD. 1 hit.
    [Graphical view]
    PROSITEiPS51257. PROKAR_LIPOPROTEIN. 1 hit.
    [Graphical view]

    Sequencei

    Sequence statusi: Complete.

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

    O53223-1 [UniParc]FASTAAdd to Basket

    « Hide

    MPKVGIAAQA GRTRVRRAWL TALMMTAVMI GAVACGSGRG PAPIKVIADK    50
    GTPFADLLVP KLTASVTDGA VGVTVDAPVS VTAADGVLAA VTMVNDNGRP 100
    VAGRLSPDGL RWSTTEQLGY NRRYTLNATA LGLGGAATRQ LTFQTSSPAH 150
    LTMPYVMPGD GEVVGVGEPV AIRFDENIAD RGAAEKAIKI TTNPPVEGAF 200
    YWLNNREVRW RPEHFWKPGT AVDVAVNTYG VDLGEGMFGE DNVQTHFTIG 250
    DEVIATADDN TKILTVRVNG EVVKSMPTSM GKDSTPTANG IYIVGSRYKH 300
    IIMDSSTYGV PVNSPNGYRT DVDWATQISY SGVFVHSAPW SVGAQGHTNT 350
    SHGCLNVSPS NAQWFYDHVK RGDIVEVVNT VGGTLPGIDG LGDWNIPWDQ 400
    WRAGNAKA 408
    Length:408
    Mass (Da):43,366
    Last modified:June 1, 1998 - v1
    Checksum:i8705AA9136A0D495
    GO

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    AE000516 Genomic DNA. Translation: AAK46901.1.
    JLBH01000002 Genomic DNA. Translation: KBN13754.1.
    PIRiC70870.
    RefSeqiNP_337087.1. NC_002755.2.

    Genome annotation databases

    EnsemblBacteriaiAAK46901; AAK46901; MT2594.
    CCP45312; CCP45312; Rv2518c.
    GeneIDi925826.
    KEGGimtc:MT2594.
    mtu:Rv2518c.
    mtv:RVBD_2518c.
    PATRICi18127458. VBIMycTub22151_2833.

    Cross-referencesi

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    AE000516 Genomic DNA. Translation: AAK46901.1 .
    JLBH01000002 Genomic DNA. Translation: KBN13754.1 .
    PIRi C70870.
    RefSeqi NP_337087.1. NC_002755.2.

    3D structure databases

    Select the link destinations:
    PDBe
    RCSB PDB
    PDBj
    Links Updated
    Entry Method Resolution (Å) Chain Positions PDBsum
    3TUR X-ray 1.72 A/B 122-408 [» ]
    3TX4 X-ray 2.32 A/B 122-408 [» ]
    3U1P X-ray 2.80 A/B 122-408 [» ]
    3U1Q X-ray 2.40 A/B 122-408 [» ]
    3VAE X-ray 2.80 A/B 122-408 [» ]
    ProteinModelPortali O53223.
    SMRi O53223. Positions 58-406.
    ModBasei Search...
    MobiDBi Search...

    Protein-protein interaction databases

    STRINGi 83332.Rv2518c.

    Protocols and materials databases

    Structural Biology Knowledgebase Search...

    Genome annotation databases

    EnsemblBacteriai AAK46901 ; AAK46901 ; MT2594 .
    CCP45312 ; CCP45312 ; Rv2518c .
    GeneIDi 925826.
    KEGGi mtc:MT2594.
    mtu:Rv2518c.
    mtv:RVBD_2518c.
    PATRICi 18127458. VBIMycTub22151_2833.

    Phylogenomic databases

    HOGENOMi HOG000241380.
    OMAi NAEWFYD.
    OrthoDBi EOG66QKTJ.

    Enzyme and pathway databases

    UniPathwayi UPA00219 .
    BioCyci MTBRV:RV2518C-MONOMER.

    Family and domain databases

    InterProi IPR005490. LD_TPept_cat_dom.
    [Graphical view ]
    Pfami PF03734. YkuD. 1 hit.
    [Graphical view ]
    PROSITEi PS51257. PROKAR_LIPOPROTEIN. 1 hit.
    [Graphical view ]
    ProtoNeti Search...

    Publicationsi

    1. Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
      Strain: CDC 1551 / Oshkosh.
    2. Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
      Strain: CDC 1551 / Oshkosh.
    3. "The Mycobacterium tuberculosis protein LdtMt2 is a nonclassical transpeptidase required for virulence and resistance to amoxicillin."
      Gupta R., Lavollay M., Mainardi J.L., Arthur M., Bishai W.R., Lamichhane G.
      Nat. Med. 16:466-469(2010) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION, CATALYTIC ACTIVITY, SUBSTRATE SPECIFICITY, DISRUPTION PHENOTYPE, INDUCTION.
      Strain: CDC 1551 / Oshkosh.
    4. "Nonclassical transpeptidases of Mycobacterium tuberculosis alter cell size, morphology, the cytosolic matrix, protein localization, virulence, and resistance to beta-lactams."
      Schoonmaker M.K., Bishai W.R., Lamichhane G.
      J. Bacteriol. 196:1394-1402(2014) [PubMed] [Europe PMC] [Abstract]
      Cited for: DISRUPTION PHENOTYPE.
      Strain: CDC 1551 / Oshkosh.
    5. "The structure of Mycobacterium tuberculosis L,D-transpeptidase 2 provides insights into targeting the cell wall of persisters."
      Erdemli S.B., Gupta R., Lamichhane G., Bishai W., Amzel L.M., Bianchet M.A.
      Submitted (SEP-2011) to the PDB data bank
      Cited for: X-RAY CRYSTALLOGRAPHY (2.40 ANGSTROMS) OF 122-408.
      Strain: CDC 1551 / Oshkosh.
    6. "Targeting the cell wall of Mycobacterium tuberculosis: structure and mechanism of L,D-transpeptidase 2."
      Erdemli S.B., Gupta R., Bishai W.R., Lamichhane G., Amzel L.M., Bianchet M.A.
      Structure 20:2103-2115(2012) [PubMed] [Europe PMC] [Abstract]
      Cited for: X-RAY CRYSTALLOGRAPHY (1.72 ANGSTROMS) OF 122-408 OF WILD-TYPE AND MUTANT ALA-354 IN COMPLEX WITH A PEPTIDOGLYCAN FRAGMENT, REACTION MECHANISM, ACTIVE SITE, SUBUNIT.
      Strain: CDC 1551 / Oshkosh.

    Entry informationi

    Entry nameiLDT2_MYCTO
    AccessioniPrimary (citable) accession number: O53223
    Secondary accession number(s): F2GH40, Q7D6Z8
    Entry historyi
    Integrated into UniProtKB/Swiss-Prot: October 1, 2014
    Last sequence update: June 1, 1998
    Last modified: October 1, 2014
    This is version 84 of the entry and version 1 of the sequence. [Complete history]
    Entry statusiReviewed (UniProtKB/Swiss-Prot)
    Annotation programProkaryotic Protein Annotation Program

    Miscellaneousi

    Keywords - Technical termi

    3D-structure, Complete proteome

    Documents

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

    External Data

    Dasty 3