LDT2_MYCTU
ID LDT2_MYCTU Reviewed; 408 AA.
AC I6Y9J2;
DT 01-OCT-2014, integrated into UniProtKB/Swiss-Prot.
DT 03-OCT-2012, sequence version 1.
DT 03-AUG-2022, entry version 62.
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; Synonyms=lppS; OrderedLocusNames=Rv2518c, RVBD_2518c;
GN ORFNames=P425_02624;
OS Mycobacterium tuberculosis (strain ATCC 25618 / H37Rv).
OC Bacteria; Actinobacteria; Corynebacteriales; Mycobacteriaceae;
OC Mycobacterium; Mycobacterium tuberculosis complex.
OX NCBI_TaxID=83332;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=ATCC 25618 / H37Rv;
RX PubMed=9634230; DOI=10.1038/31159;
RA Cole S.T., Brosch R., Parkhill J., Garnier T., Churcher C.M., Harris D.E.,
RA Gordon S.V., Eiglmeier K., Gas S., Barry C.E. III, Tekaia F., Badcock K.,
RA Basham D., Brown D., Chillingworth T., Connor R., Davies R.M., Devlin K.,
RA Feltwell T., Gentles S., Hamlin N., Holroyd S., Hornsby T., Jagels K.,
RA Krogh A., McLean J., Moule S., Murphy L.D., Oliver S., Osborne J.,
RA Quail M.A., Rajandream M.A., Rogers J., Rutter S., Seeger K., Skelton S.,
RA Squares S., Squares R., Sulston J.E., Taylor K., Whitehead S.,
RA Barrell B.G.;
RT "Deciphering the biology of Mycobacterium tuberculosis from the complete
RT genome sequence.";
RL Nature 393:537-544(1998).
RN [2]
RP IDENTIFICATION, AND GENOME REANNOTATION.
RC STRAIN=ATCC 25618 / H37Rv;
RA Lew J.M.;
RL Submitted (DEC-2012) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=ATCC 25618 / H37Rv;
RG The Broad Institute Genome Sequencing Platform;
RA Galagan J., Kreiswirth B., Dobos K., Fortune S., Fitzgerald M., Young S.K.,
RA Zeng Q., Gargeya S., Abouelleil A., Alvarado L., Berlin A.M., Chapman S.B.,
RA Gainer-Dewar J., Goldberg J., Gnerre S., Griggs A., Gujja S., Hansen M.,
RA Howarth C., Imamovic A., Larimer J., McCowan C., Murphy C., Pearson M.,
RA Poon T., Priest M., Roberts A., Saif S., Shea T., Sykes S., Wortman J.,
RA Nusbaum C., Birren B.;
RT "The genome sequence of Mycobacterium tuberculosis H37Rv.";
RL Submitted (NOV-2013) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=ATCC 25618 / H37Rv;
RG The Broad Institute Genomics Platform;
RG The Broad Institute Genome Sequencing Center for Infectious Disease;
RA Earl A.M., Kreiswirth B., Gomez J., Victor T., Desjardins C., Abeel T.,
RA Young S., Zeng Q., Gargeya S., Abouelleil A., Alvarado L., Chapman S.B.,
RA Gainer-Dewar J., Goldberg J., Griggs A., Gujja S., Hansen M., Howarth C.,
RA Imamovic A., Larimer J., Murphy C., Naylor J., Pearson M., Poon T.W.,
RA Priest M., Roberts A., Saif S., Shea T., Sykes S., Wortman J., Nusbaum C.,
RA Birren B.;
RT "The genome sequence of Mycobacterium tuberculosis H37Rv.";
RL Submitted (APR-2014) to the EMBL/GenBank/DDBJ databases.
RN [5]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC STRAIN=ATCC 25618 / H37Rv;
RX PubMed=21969609; DOI=10.1074/mcp.m111.011627;
RA Kelkar D.S., Kumar D., Kumar P., Balakrishnan L., Muthusamy B., Yadav A.K.,
RA Shrivastava P., Marimuthu A., Anand S., Sundaram H., Kingsbury R.,
RA Harsha H.C., Nair B., Prasad T.S., Chauhan D.S., Katoch K., Katoch V.M.,
RA Kumar P., Chaerkady R., Ramachandran S., Dash D., Pandey A.;
RT "Proteogenomic analysis of Mycobacterium tuberculosis by high resolution
RT mass spectrometry.";
RL Mol. Cell. Proteomics 10:M111.011627-M111.011627(2011).
RN [6]
RP FUNCTION, CATALYTIC ACTIVITY, SUBSTRATE SPECIFICITY, AND ACTIVITY
RP REGULATION.
RC STRAIN=ATCC 25618 / H37Rv;
RX PubMed=24041897; DOI=10.1128/aac.01663-13;
RA Cordillot M., Dubee V., Triboulet S., Dubost L., Marie A., Hugonnet J.E.,
RA Arthur M., Mainardi J.L.;
RT "In vitro cross-linking of Mycobacterium tuberculosis peptidoglycan by L,D-
RT transpeptidases and inactivation of these enzymes by carbapenems.";
RL Antimicrob. Agents Chemother. 57:5940-5945(2013).
RN [7]
RP X-RAY CRYSTALLOGRAPHY (1.79 ANGSTROMS) OF 131-408 OF APOENZYME AND IN
RP COMPLEXES WITH MEROPENEM AND CALCIUM, ACTIVITY REGULATION, ACTIVE SITE, AND
RP DOMAIN.
RC STRAIN=ATCC 25618 / H37Rv;
RX PubMed=23519417; DOI=10.1107/s0907444912048998;
RA Kim H.S., Kim J., Im H.N., Yoon J.Y., An D.R., Yoon H.J., Kim J.Y.,
RA Min H.K., Kim S.J., Lee J.Y., Han B.W., Suh S.W.;
RT "Structural basis for the inhibition of Mycobacterium tuberculosis L,D-
RT transpeptidase by meropenem, a drug effective against extensively drug-
RT resistant strains.";
RL Acta Crystallogr. D 69:420-431(2013).
RN [8]
RP X-RAY CRYSTALLOGRAPHY (1.46 ANGSTROMS) OF 55-408, AND DOMAIN.
RC STRAIN=ATCC 25618 / H37Rv;
RX PubMed=23519418; DOI=10.1107/s0907444912049268;
RA Both D., Steiner E.M., Stadler D., Lindqvist Y., Schnell R., Schneider G.;
RT "Structure of LdtMt2, an L,D-transpeptidase from Mycobacterium
RT tuberculosis.";
RL Acta Crystallogr. D 69:432-441(2013).
RN [9]
RP X-RAY CRYSTALLOGRAPHY (1.40 ANGSTROMS) OF 55-408 OF APOENZYME AND IN
RP COMPLEX WITH MEROPENEM, AND MUTAGENESIS OF TYR-318.
RC STRAIN=ATCC 25618 / H37Rv;
RX PubMed=23588382; DOI=10.1038/cr.2013.53;
RA Li W.J., Li D.F., Hu Y.L., Zhang X.E., Bi L.J., Wang D.C.;
RT "Crystal structure of L,D-transpeptidase LdtMt2 in complex with meropenem
RT reveals the mechanism of carbapenem against Mycobacterium tuberculosis.";
RL Cell Res. 23:728-731(2013).
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. {ECO:0000269|PubMed:24041897}.
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; imipenem is the most efficient drug for
CC in vitro LdtMt2 inactivation. {ECO:0000269|PubMed:23519417,
CC ECO:0000269|PubMed:24041897}.
CC -!- PATHWAY: Cell wall biogenesis; peptidoglycan biosynthesis.
CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000255|PROSITE-
CC ProRule:PRU00303}; Lipid-anchor {ECO:0000255|PROSITE-ProRule:PRU00303}.
CC -!- DOMAIN: Consists of two tandem immunoglobulin-like Big_5 domains in the
CC N-terminal region (residues 56-145 and 150-250), followed by a L,D-
CC transpeptidase catalytic domain (residues 251-378) and a C-terminal
CC tail (residues 379-408). {ECO:0000269|PubMed:23519417,
CC ECO:0000269|PubMed:23519418}.
CC -!- MISCELLANEOUS: The peptidoglycan structure of stationary-phase
CC M.tuberculosis is atypical since it contains a majority (80%) of 3->3
CC cross-links synthesized by L,D-transpeptidases that predominate over
CC the 4->3 cross-links formed by the D,D-transpeptidase activity of
CC classical penicillin-binding proteins (PubMed:18408028). In fact, 3-3
CC cross-linkages predominate throughout all growth phases and the ratio
CC of 4-3/3-3 linkages does not vary significantly under any growth
CC condition (PubMed:22906310).
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DR EMBL; CP003248; AFN50487.1; -; Genomic_DNA.
DR EMBL; AL123456; CCP45312.1; -; Genomic_DNA.
DR EMBL; JLDD01000032; KBJ30847.1; -; Genomic_DNA.
DR RefSeq; NP_217034.1; NC_000962.3.
DR RefSeq; WP_003412938.1; NZ_NVQJ01000032.1.
DR PDB; 3VYN; X-ray; 2.50 A; A/B=55-408.
DR PDB; 3VYO; X-ray; 1.80 A; A/B=140-408.
DR PDB; 3VYP; X-ray; 1.40 A; A/B=140-408.
DR PDB; 4GSQ; X-ray; 1.80 A; A=131-408.
DR PDB; 4GSR; X-ray; 1.79 A; A=131-408.
DR PDB; 4GSU; X-ray; 2.00 A; A/B=131-408.
DR PDB; 4HU2; X-ray; 1.46 A; A=55-250.
DR PDB; 4HUC; X-ray; 1.86 A; A/B=149-408.
DR PDB; 4QR7; X-ray; 2.30 A; A=57-408.
DR PDB; 4QRA; X-ray; 2.29 A; A/B=57-408.
DR PDB; 4QRB; X-ray; 1.64 A; A=57-408.
DR PDB; 4QTF; X-ray; 2.00 A; A=59-407.
DR PDB; 5D7H; X-ray; 2.49 A; A/B=56-407.
DR PDB; 5DC2; X-ray; 2.18 A; A/B=56-408.
DR PDB; 5DCC; X-ray; 2.45 A; A/B=56-408.
DR PDB; 5DU7; X-ray; 1.79 A; A/B/C/D=42-408.
DR PDB; 5DUJ; X-ray; 2.17 A; A/B=42-408.
DR PDB; 5DVP; X-ray; 2.18 A; A/B=58-407.
DR PDB; 5DZJ; X-ray; 2.10 A; A/B=42-408.
DR PDB; 5DZP; X-ray; 2.19 A; A/B=42-408.
DR PDB; 5E1G; X-ray; 1.85 A; A/B=42-408.
DR PDB; 5E1I; X-ray; 2.00 A; A/B=42-408.
DR PDB; 5K69; X-ray; 2.00 A; A/B=1-408.
DR PDB; 5LB1; X-ray; 1.55 A; A/B=149-408.
DR PDB; 5LBG; X-ray; 1.54 A; A/B=149-408.
DR PDB; 6IYV; X-ray; 1.50 A; A/B=140-408.
DR PDB; 6IYW; X-ray; 1.60 A; A/B/C/D/E/F=140-408.
DR PDB; 6LQB; X-ray; 1.70 A; A/B=140-408.
DR PDB; 7A0Z; X-ray; 1.45 A; A/B=149-408.
DR PDB; 7A10; X-ray; 1.85 A; A/B=149-408.
DR PDB; 7A11; X-ray; 1.65 A; A/B=150-408.
DR PDB; 7A1C; X-ray; 1.77 A; A/B=150-408.
DR PDB; 7A1E; X-ray; 1.77 A; A/B=150-408.
DR PDB; 7KEM; X-ray; 1.77 A; A/B=1-408.
DR PDBsum; 3VYN; -.
DR PDBsum; 3VYO; -.
DR PDBsum; 3VYP; -.
DR PDBsum; 4GSQ; -.
DR PDBsum; 4GSR; -.
DR PDBsum; 4GSU; -.
DR PDBsum; 4HU2; -.
DR PDBsum; 4HUC; -.
DR PDBsum; 4QR7; -.
DR PDBsum; 4QRA; -.
DR PDBsum; 4QRB; -.
DR PDBsum; 4QTF; -.
DR PDBsum; 5D7H; -.
DR PDBsum; 5DC2; -.
DR PDBsum; 5DCC; -.
DR PDBsum; 5DU7; -.
DR PDBsum; 5DUJ; -.
DR PDBsum; 5DVP; -.
DR PDBsum; 5DZJ; -.
DR PDBsum; 5DZP; -.
DR PDBsum; 5E1G; -.
DR PDBsum; 5E1I; -.
DR PDBsum; 5K69; -.
DR PDBsum; 5LB1; -.
DR PDBsum; 5LBG; -.
DR PDBsum; 6IYV; -.
DR PDBsum; 6IYW; -.
DR PDBsum; 6LQB; -.
DR PDBsum; 7A0Z; -.
DR PDBsum; 7A10; -.
DR PDBsum; 7A11; -.
DR PDBsum; 7A1C; -.
DR PDBsum; 7A1E; -.
DR PDBsum; 7KEM; -.
DR AlphaFoldDB; I6Y9J2; -.
DR SMR; I6Y9J2; -.
DR STRING; 83332.Rv2518c; -.
DR PaxDb; I6Y9J2; -.
DR PRIDE; I6Y9J2; -.
DR DNASU; 888160; -.
DR GeneID; 888160; -.
DR KEGG; mtu:Rv2518c; -.
DR KEGG; mtv:RVBD_2518c; -.
DR TubercuList; Rv2518c; -.
DR eggNOG; COG1376; Bacteria.
DR OMA; WHWVDDK; -.
DR PhylomeDB; I6Y9J2; -.
DR BRENDA; 2.3.2.B14; 3445.
DR UniPathway; UPA00219; -.
DR Proteomes; UP000001584; Chromosome.
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; IBA:GO_Central.
DR GO; GO:0071555; P:cell wall organization; IEA:UniProtKB-KW.
DR GO; GO:0018104; P:peptidoglycan-protein cross-linking; IBA:GO_Central.
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; Reference proteome; Signal;
KW Transferase.
FT SIGNAL 1..34
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00303"
FT CHAIN 35..408
FT /note="L,D-transpeptidase 2"
FT /id="PRO_0000430334"
FT DOMAIN 259..377
FT /note="YkuD"
FT ACT_SITE 336
FT /note="Proton donor/acceptor"
FT /evidence="ECO:0000305|PubMed:23519417"
FT ACT_SITE 354
FT /note="Nucleophile"
FT /evidence="ECO:0000269|PubMed:23519417"
FT BINDING 232
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT BINDING 235
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT BINDING 236
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT BINDING 318
FT /ligand="substrate"
FT /evidence="ECO:0000250"
FT BINDING 331..332
FT /ligand="substrate"
FT /evidence="ECO:0000250"
FT BINDING 356
FT /ligand="substrate"
FT /evidence="ECO:0000250"
FT SITE 354
FT /note="Binds to carbapenem drug (covalent)"
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 MUTAGEN 318
FT /note="Y->A,F: Decreases stability of the covalent enzyme-
FT meropenem adduct."
FT /evidence="ECO:0000269|PubMed:23588382"
FT STRAND 61..66
FT /evidence="ECO:0007829|PDB:4QRB"
FT STRAND 71..73
FT /evidence="ECO:0007829|PDB:3VYN"
FT STRAND 75..77
FT /evidence="ECO:0007829|PDB:5E1G"
FT STRAND 80..94
FT /evidence="ECO:0007829|PDB:4QRB"
FT STRAND 96..98
FT /evidence="ECO:0007829|PDB:5K69"
FT STRAND 103..105
FT /evidence="ECO:0007829|PDB:4QRB"
FT STRAND 109..114
FT /evidence="ECO:0007829|PDB:4QRB"
FT STRAND 123..132
FT /evidence="ECO:0007829|PDB:4QRB"
FT STRAND 135..145
FT /evidence="ECO:0007829|PDB:4QRB"
FT STRAND 150..152
FT /evidence="ECO:0007829|PDB:6IYW"
FT STRAND 154..158
FT /evidence="ECO:0007829|PDB:3VYP"
FT STRAND 162..164
FT /evidence="ECO:0007829|PDB:6IYV"
FT STRAND 170..176
FT /evidence="ECO:0007829|PDB:3VYP"
FT HELIX 181..186
FT /evidence="ECO:0007829|PDB:3VYP"
FT STRAND 188..194
FT /evidence="ECO:0007829|PDB:3VYP"
FT STRAND 198..214
FT /evidence="ECO:0007829|PDB:3VYP"
FT STRAND 221..226
FT /evidence="ECO:0007829|PDB:3VYP"
FT STRAND 232..234
FT /evidence="ECO:0007829|PDB:7A1C"
FT STRAND 237..239
FT /evidence="ECO:0007829|PDB:4QRB"
FT STRAND 243..249
FT /evidence="ECO:0007829|PDB:3VYP"
FT STRAND 253..258
FT /evidence="ECO:0007829|PDB:3VYP"
FT TURN 259..262
FT /evidence="ECO:0007829|PDB:3VYP"
FT STRAND 263..268
FT /evidence="ECO:0007829|PDB:3VYP"
FT STRAND 271..277
FT /evidence="ECO:0007829|PDB:3VYP"
FT STRAND 289..293
FT /evidence="ECO:0007829|PDB:3VYP"
FT STRAND 297..304
FT /evidence="ECO:0007829|PDB:3VYP"
FT HELIX 305..308
FT /evidence="ECO:0007829|PDB:3VYP"
FT STRAND 312..316
FT /evidence="ECO:0007829|PDB:3VYP"
FT STRAND 319..327
FT /evidence="ECO:0007829|PDB:3VYP"
FT STRAND 334..337
FT /evidence="ECO:0007829|PDB:3VYP"
FT HELIX 339..341
FT /evidence="ECO:0007829|PDB:3VYP"
FT TURN 342..347
FT /evidence="ECO:0007829|PDB:3VYP"
FT STRAND 351..357
FT /evidence="ECO:0007829|PDB:3VYP"
FT HELIX 359..368
FT /evidence="ECO:0007829|PDB:3VYP"
FT STRAND 374..379
FT /evidence="ECO:0007829|PDB:3VYP"
FT STRAND 389..391
FT /evidence="ECO:0007829|PDB:3VYP"
FT HELIX 393..395
FT /evidence="ECO:0007829|PDB:3VYP"
FT HELIX 398..403
FT /evidence="ECO:0007829|PDB:3VYP"
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
