LDT2_MYCTO
ID LDT2_MYCTO Reviewed; 408 AA.
AC O53223; F2GH40; Q7D6Z8;
DT 01-OCT-2014, integrated into UniProtKB/Swiss-Prot.
DT 01-JUN-1998, sequence version 1.
DT 03-AUG-2022, entry version 117.
DE RecName: Full=L,D-transpeptidase 2;
DE Short=LDT 2;
DE EC=2.3.2.-;
DE AltName: Full=Ldt(Mt2);
DE Flags: Precursor;
GN Name=ldtB; OrderedLocusNames=MT2594; ORFNames=V735_02606;
OS Mycobacterium tuberculosis (strain CDC 1551 / Oshkosh).
OC Bacteria; Actinobacteria; Corynebacteriales; Mycobacteriaceae;
OC Mycobacterium; Mycobacterium tuberculosis complex.
OX NCBI_TaxID=83331;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=CDC 1551 / Oshkosh;
RX PubMed=12218036; DOI=10.1128/jb.184.19.5479-5490.2002;
RA Fleischmann R.D., Alland D., Eisen J.A., Carpenter L., White O.,
RA Peterson J.D., DeBoy R.T., Dodson R.J., Gwinn M.L., Haft D.H., Hickey E.K.,
RA Kolonay J.F., Nelson W.C., Umayam L.A., Ermolaeva M.D., Salzberg S.L.,
RA Delcher A., Utterback T.R., Weidman J.F., Khouri H.M., Gill J., Mikula A.,
RA Bishai W., Jacobs W.R. Jr., Venter J.C., Fraser C.M.;
RT "Whole-genome comparison of Mycobacterium tuberculosis clinical and
RT laboratory strains.";
RL J. Bacteriol. 184:5479-5490(2002).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=CDC 1551 / Oshkosh;
RG The Broad Institute Genomics Platform;
RG The Broad Institute Genome Sequencing Center for Infectious Disease;
RA Earl A.M., Hung D., Gomez D., Hsueh P.R., Rozo J.C., Zambrano M.M.,
RA Desjardins C., Abeel T., Young S., Zeng Q., Gargeya S., Abouelleil A.,
RA Alvarado L., Chapman S.B., Gainer-Dewar J., Goldberg J., Griggs A.,
RA Gujja S., Hansen M., Howarth C., Imamovic A., Larimer J., Murphy C.,
RA Naylor J., Pearson M., Poon T.W., Priest M., Roberts A., Saif S., Shea T.,
RA Sykes S., Wortman J., Nusbaum C., Birren B.;
RT "The genome sequence of Mycobacterium tuberculosis CDC1551.";
RL Submitted (APR-2014) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP FUNCTION, CATALYTIC ACTIVITY, SUBSTRATE SPECIFICITY, DISRUPTION PHENOTYPE,
RP AND INDUCTION.
RC STRAIN=CDC 1551 / Oshkosh;
RX PubMed=20305661; DOI=10.1038/nm.2120;
RA Gupta R., Lavollay M., Mainardi J.L., Arthur M., Bishai W.R.,
RA Lamichhane G.;
RT "The Mycobacterium tuberculosis protein LdtMt2 is a nonclassical
RT transpeptidase required for virulence and resistance to amoxicillin.";
RL Nat. Med. 16:466-469(2010).
RN [4]
RP DISRUPTION PHENOTYPE.
RC STRAIN=CDC 1551 / Oshkosh;
RX PubMed=24464457; DOI=10.1128/jb.01396-13;
RA Schoonmaker M.K., Bishai W.R., Lamichhane G.;
RT "Nonclassical transpeptidases of Mycobacterium tuberculosis alter cell
RT size, morphology, the cytosolic matrix, protein localization, virulence,
RT and resistance to beta-lactams.";
RL J. Bacteriol. 196:1394-1402(2014).
RN [5]
RP X-RAY CRYSTALLOGRAPHY (2.40 ANGSTROMS) OF 122-408.
RC STRAIN=CDC 1551 / Oshkosh;
RA Erdemli S.B., Gupta R., Lamichhane G., Bishai W., Amzel L.M.,
RA Bianchet M.A.;
RT "The structure of Mycobacterium tuberculosis L,D-transpeptidase 2 provides
RT insights into targeting the cell wall of persisters.";
RL Submitted (SEP-2011) to the PDB data bank.
RN [6]
RP X-RAY CRYSTALLOGRAPHY (1.72 ANGSTROMS) OF 122-408 OF WILD-TYPE AND MUTANT
RP ALA-354 IN COMPLEX WITH A PEPTIDOGLYCAN FRAGMENT, REACTION MECHANISM,
RP ACTIVE SITE, AND SUBUNIT.
RC STRAIN=CDC 1551 / Oshkosh;
RX PubMed=23103390; DOI=10.1016/j.str.2012.09.016;
RA Erdemli S.B., Gupta R., Bishai W.R., Lamichhane G., Amzel L.M.,
RA Bianchet M.A.;
RT "Targeting the cell wall of Mycobacterium tuberculosis: structure and
RT mechanism of L,D-transpeptidase 2.";
RL Structure 20:2103-2115(2012).
CC -!- FUNCTION: Generates 3->3 cross-links in peptidoglycan, catalyzing the
CC cleavage of the mDap(3)-D-Ala(4) bond of a tetrapeptide donor stem and
CC the formation of a bond between the carbonyl of mDap(3) of the donor
CC stem and the side chain of mDap(3) of the acceptor stem. Is specific
CC for donor substrates containing a stem tetrapeptide since it cannot use
CC pentapeptide stems. Is essential for virulence in a mouse model of
CC acute infection. {ECO:0000269|PubMed:20305661}.
CC -!- ACTIVITY REGULATION: Is irreversibly inactivated by the beta-lactams
CC carbapenems via the formation of a covalent adduct resulting from
CC acylation of the catalytic Cys. {ECO:0000250}.
CC -!- PATHWAY: Cell wall biogenesis; peptidoglycan biosynthesis.
CC -!- SUBUNIT: Monomer. {ECO:0000305|PubMed:23103390}.
CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000255|PROSITE-
CC ProRule:PRU00303}; Lipid-anchor {ECO:0000255|PROSITE-ProRule:PRU00303}.
CC -!- INDUCTION: Is expressed at a level higher than other LDT paralogs at
CC all phases of growth. {ECO:0000269|PubMed:20305661}.
CC -!- DISRUPTION PHENOTYPE: Inactivation of this gene leads to altered colony
CC morphology and growth, attenuation of persistence and increased
CC susceptibility to amoxicillin-clavulanate both in vitro and in the
CC mouse model during the chronic phase of infection. Loss of both ldtMt1
CC and ldtMt2 results in phenotypes that are unique and/or severe compared
CC to the single mutants lacking only ldtMt1 or ldtMt2. The double gene
CC deletion severely alters cellular shape, intracellular morphology,
CC physiology and virulence: the length of mutant cells are shorter than
CC wild-type, they have deep surface depressions and bulges, they possess
CC large unstained vacuole-like structures, the thickness of the
CC peptidoglycan layer is smaller, the protein localization is altered,
CC and in vitro and in vivo growth and virulence are severely attenuated.
CC Moreover, double-mutant cells are more sensitive to vancomycin and
CC amoxicillin-clavulanate. {ECO:0000269|PubMed:20305661,
CC ECO:0000269|PubMed:24464457}.
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DR EMBL; AE000516; AAK46901.1; -; Genomic_DNA.
DR EMBL; JLBH01000002; KBN13754.1; -; Genomic_DNA.
DR PIR; C70870; C70870.
DR RefSeq; WP_003412938.1; NZ_KK341227.1.
DR PDB; 3TUR; X-ray; 1.72 A; A/B=122-408.
DR PDB; 3TX4; X-ray; 2.32 A; A/B=122-408.
DR PDB; 3U1P; X-ray; 2.80 A; A/B=122-408.
DR PDB; 3U1Q; X-ray; 2.40 A; A/B=122-408.
DR PDB; 3VAE; X-ray; 2.80 A; A/B=122-408.
DR PDBsum; 3TUR; -.
DR PDBsum; 3TX4; -.
DR PDBsum; 3U1P; -.
DR PDBsum; 3U1Q; -.
DR PDBsum; 3VAE; -.
DR AlphaFoldDB; O53223; -.
DR SMR; O53223; -.
DR EnsemblBacteria; AAK46901; AAK46901; MT2594.
DR KEGG; mtc:MT2594; -.
DR PATRIC; fig|83331.31.peg.2797; -.
DR HOGENOM; CLU_039404_3_0_11; -.
DR InParanoid; O53223; -.
DR BRENDA; 2.3.2.12; 3445.
DR BRENDA; 2.3.2.B14; 3445.
DR UniPathway; UPA00219; -.
DR Proteomes; UP000001020; Chromosome.
DR GO; GO:0009274; C:peptidoglycan-based cell wall; HDA:MTBBASE.
DR GO; GO:0005886; C:plasma membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0016746; F:acyltransferase activity; IEA:UniProtKB-KW.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0071972; F:peptidoglycan L,D-transpeptidase activity; IDA:MTBBASE.
DR GO; GO:0071555; P:cell wall organization; IEA:UniProtKB-KW.
DR GO; GO:0009252; P:peptidoglycan biosynthetic process; IEA:UniProtKB-UniPathway.
DR GO; GO:0000270; P:peptidoglycan metabolic process; IDA:MTBBASE.
DR GO; GO:0009273; P:peptidoglycan-based cell wall biogenesis; IDA:MTBBASE.
DR GO; GO:0008360; P:regulation of cell shape; IEA:UniProtKB-KW.
DR CDD; cd16913; YkuD_like; 1.
DR Gene3D; 2.40.440.10; -; 1.
DR InterPro; IPR041280; Big_10.
DR InterPro; IPR005490; LD_TPept_cat_dom.
DR InterPro; IPR038063; Transpep_catalytic_dom.
DR Pfam; PF17964; Big_10; 1.
DR Pfam; PF03734; YkuD; 1.
DR SUPFAM; SSF141523; SSF141523; 1.
DR PROSITE; PS51257; PROKAR_LIPOPROTEIN; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Acyltransferase; Calcium; Cell membrane; Cell shape;
KW Cell wall biogenesis/degradation; Lipoprotein; Membrane; Metal-binding;
KW Palmitate; Peptidoglycan synthesis; Signal; Transferase; Virulence.
FT SIGNAL 1..34
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00303"
FT CHAIN 35..408
FT /note="L,D-transpeptidase 2"
FT /id="PRO_0000430333"
FT DOMAIN 259..377
FT /note="YkuD"
FT ACT_SITE 336
FT /note="Proton donor/acceptor"
FT /evidence="ECO:0000305|PubMed:23103390"
FT ACT_SITE 354
FT /note="Nucleophile"
FT /evidence="ECO:0000269|PubMed:23103390"
FT BINDING 232
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /evidence="ECO:0000250"
FT BINDING 235
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /evidence="ECO:0000250"
FT BINDING 236
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /evidence="ECO:0000250"
FT BINDING 318
FT /ligand="substrate"
FT BINDING 331..332
FT /ligand="substrate"
FT BINDING 356
FT /ligand="substrate"
FT SITE 354
FT /note="Binds to carbapenem drug (covalent)"
FT /evidence="ECO:0000250"
FT LIPID 35
FT /note="N-palmitoyl cysteine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00303"
FT LIPID 35
FT /note="S-diacylglycerol cysteine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00303"
FT STRAND 125..127
FT /evidence="ECO:0007829|PDB:3TX4"
FT STRAND 154..158
FT /evidence="ECO:0007829|PDB:3TUR"
FT STRAND 170..176
FT /evidence="ECO:0007829|PDB:3TUR"
FT HELIX 181..187
FT /evidence="ECO:0007829|PDB:3TUR"
FT STRAND 188..194
FT /evidence="ECO:0007829|PDB:3TUR"
FT STRAND 198..204
FT /evidence="ECO:0007829|PDB:3TUR"
FT STRAND 207..214
FT /evidence="ECO:0007829|PDB:3TUR"
FT STRAND 221..227
FT /evidence="ECO:0007829|PDB:3TUR"
FT STRAND 238..240
FT /evidence="ECO:0007829|PDB:3TUR"
FT STRAND 242..249
FT /evidence="ECO:0007829|PDB:3TUR"
FT STRAND 253..258
FT /evidence="ECO:0007829|PDB:3TUR"
FT TURN 259..261
FT /evidence="ECO:0007829|PDB:3TUR"
FT STRAND 263..268
FT /evidence="ECO:0007829|PDB:3TUR"
FT STRAND 271..277
FT /evidence="ECO:0007829|PDB:3TUR"
FT STRAND 289..293
FT /evidence="ECO:0007829|PDB:3TUR"
FT STRAND 297..304
FT /evidence="ECO:0007829|PDB:3TUR"
FT HELIX 305..308
FT /evidence="ECO:0007829|PDB:3TUR"
FT STRAND 319..327
FT /evidence="ECO:0007829|PDB:3TUR"
FT STRAND 334..337
FT /evidence="ECO:0007829|PDB:3TUR"
FT HELIX 339..341
FT /evidence="ECO:0007829|PDB:3TUR"
FT TURN 342..347
FT /evidence="ECO:0007829|PDB:3TUR"
FT STRAND 351..357
FT /evidence="ECO:0007829|PDB:3TUR"
FT HELIX 359..368
FT /evidence="ECO:0007829|PDB:3TUR"
FT STRAND 374..379
FT /evidence="ECO:0007829|PDB:3TUR"
FT STRAND 389..391
FT /evidence="ECO:0007829|PDB:3TUR"
FT HELIX 393..395
FT /evidence="ECO:0007829|PDB:3TUR"
FT HELIX 398..403
FT /evidence="ECO:0007829|PDB:3TUR"
SQ SEQUENCE 408 AA; 43366 MW; 8705AA9136A0D495 CRC64;
MPKVGIAAQA GRTRVRRAWL TALMMTAVMI GAVACGSGRG PAPIKVIADK GTPFADLLVP
KLTASVTDGA VGVTVDAPVS VTAADGVLAA VTMVNDNGRP VAGRLSPDGL RWSTTEQLGY
NRRYTLNATA LGLGGAATRQ LTFQTSSPAH LTMPYVMPGD GEVVGVGEPV AIRFDENIAD
RGAAEKAIKI TTNPPVEGAF YWLNNREVRW RPEHFWKPGT AVDVAVNTYG VDLGEGMFGE
DNVQTHFTIG DEVIATADDN TKILTVRVNG EVVKSMPTSM GKDSTPTANG IYIVGSRYKH
IIMDSSTYGV PVNSPNGYRT DVDWATQISY SGVFVHSAPW SVGAQGHTNT SHGCLNVSPS
NAQWFYDHVK RGDIVEVVNT VGGTLPGIDG LGDWNIPWDQ WRAGNAKA
