LDT1_MYCTU
ID LDT1_MYCTU Reviewed; 251 AA.
AC O53638; F2GLR2; I6X8J8; L0T5Q5;
DT 01-OCT-2014, integrated into UniProtKB/Swiss-Prot.
DT 01-JUN-1998, sequence version 1.
DT 03-AUG-2022, entry version 112.
DE RecName: Full=L,D-transpeptidase 1;
DE Short=LDT 1;
DE EC=2.3.2.-;
DE AltName: Full=Ldt(Mt1);
DE Flags: Precursor;
GN Name=ldtA; OrderedLocusNames=Rv0116c, RVBD_0116c; ORFNames=P425_00122;
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 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 [3]
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 [4]
RP INDUCTION BY STARVATION, AND IDENTIFICATION BY MASS SPECTROMETRY.
RC STRAIN=ATCC 25618 / H37Rv;
RX PubMed=11929527; DOI=10.1046/j.1365-2958.2002.02779.x;
RA Betts J.C., Lukey P.T., Robb L.C., McAdam R.A., Duncan K.;
RT "Evaluation of a nutrient starvation model of Mycobacterium tuberculosis
RT persistence by gene and protein expression profiling.";
RL Mol. Microbiol. 43:717-731(2002).
RN [5]
RP FUNCTION, CATALYTIC ACTIVITY, SUBSTRATE SPECIFICITY, AND ACTIVITY
RP REGULATION.
RC STRAIN=ATCC 25618 / H37Rv;
RX PubMed=18408028; DOI=10.1128/jb.00239-08;
RA Lavollay M., Arthur M., Fourgeaud M., Dubost L., Marie A., Veziris N.,
RA Blanot D., Gutmann L., Mainardi J.L.;
RT "The peptidoglycan of stationary-phase Mycobacterium tuberculosis
RT predominantly contains cross-links generated by L,D-transpeptidation.";
RL J. Bacteriol. 190:4360-4366(2008).
RN [6]
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 [7]
RP ACTIVITY REGULATION.
RC STRAIN=ATCC 25618 / H37Rv;
RX PubMed=22615283; DOI=10.1128/aac.00665-12;
RA Dubee V., Triboulet S., Mainardi J.L., Etheve-Quelquejeu M., Gutmann L.,
RA Marie A., Dubost L., Hugonnet J.E., Arthur M.;
RT "Inactivation of Mycobacterium tuberculosis l,d-transpeptidase LdtMt(1) by
RT carbapenems and cephalosporins.";
RL Antimicrob. Agents Chemother. 56:4189-4195(2012).
RN [8]
RP CRYSTALLIZATION.
RC STRAIN=ATCC 25618 / H37Rv;
RX PubMed=23519798; DOI=10.1107/s1744309112052141;
RA Correale S., Ruggiero A., Pedone E., Berisio R.;
RT "Expression, purification, crystallization and preliminary X-ray
RT crystallographic analysis of the L,D-transpeptidase LdtMt1 from
RT Mycobacterium tuberculosis.";
RL Acta Crystallogr. F 69:253-256(2013).
RN [9]
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 [10] {ECO:0007744|PDB:4JMN, ECO:0007744|PDB:4JMX}
RP X-RAY CRYSTALLOGRAPHY (2.20 ANGSTROMS) OF 32-251 OF APOENZYME AND IN
RP COMPLEX WITH THE CARBAPENEM IMIPENEM, SUBUNIT, DOMAIN, AND ACTIVE SITE.
RC STRAIN=ATCC 25618 / H37Rv;
RX PubMed=23999293; DOI=10.1107/s0907444913013085;
RA Correale S., Ruggiero A., Capparelli R., Pedone E., Berisio R.;
RT "Structures of free and inhibited forms of the L,D-transpeptidase LdtMt1
RT from Mycobacterium tuberculosis.";
RL Acta Crystallogr. D 69:1697-1706(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. Is thought to play a role in adaptation to the
CC nonreplicative state of M.tuberculosis. {ECO:0000269|PubMed:18408028,
CC 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; ertapenem and imipenem are the most
CC efficient drugs for in vitro LdtMt1 inactivation. Cephalosporins
CC (cefotaxime, cephalothin, and ceftriaxone) also form covalent adducts
CC with LdtMt1, although the acylation reaction was 7- to 1,000-fold
CC slower and leads to elimination of one of the drug side chains. A high
CC drug concentration (360 uM) of ceftriaxone is required for full
CC inhibition of enzyme activity. Is not inhibited by ampicillin.
CC {ECO:0000269|PubMed:18408028, ECO:0000269|PubMed:22615283,
CC ECO:0000269|PubMed:24041897}.
CC -!- PATHWAY: Cell wall biogenesis; peptidoglycan biosynthesis.
CC -!- SUBUNIT: Monomer. {ECO:0000269|PubMed:23999293}.
CC -!- SUBCELLULAR LOCATION: Periplasm {ECO:0000305}.
CC -!- INDUCTION: Up-regulated 17-fold under nutrient starvation.
CC {ECO:0000269|PubMed:11929527}.
CC -!- DOMAIN: Consists of two domains connected by a short loop, which form a
CC bent shape. The N-terminal domain (residues 32-122) resembles a c-type
CC immunoglobulin (Ig) domain, and the C-terminal contains the catalytic
CC site that is located in a tiny tunnel. {ECO:0000269|PubMed:23999293}.
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). {ECO:0000305|PubMed:18408028}.
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DR EMBL; CP003248; AFN47964.1; -; Genomic_DNA.
DR EMBL; AL123456; CCP42841.1; -; Genomic_DNA.
DR EMBL; JLDD01000001; KBJ41222.1; -; Genomic_DNA.
DR RefSeq; NP_214630.1; NC_000962.3.
DR RefSeq; WP_003400856.1; NZ_NVQJ01000062.1.
DR PDB; 4JMN; X-ray; 2.20 A; A=32-251.
DR PDB; 4JMX; X-ray; 2.55 A; A=32-251.
DR PDB; 5E51; X-ray; 2.25 A; A/B/C/D=32-251.
DR PDB; 5E5L; X-ray; 1.89 A; A/B/C/D=32-251.
DR PDBsum; 4JMN; -.
DR PDBsum; 4JMX; -.
DR PDBsum; 5E51; -.
DR PDBsum; 5E5L; -.
DR AlphaFoldDB; O53638; -.
DR SMR; O53638; -.
DR STRING; 83332.Rv0116c; -.
DR PaxDb; O53638; -.
DR PRIDE; O53638; -.
DR DNASU; 886900; -.
DR GeneID; 886900; -.
DR KEGG; mtu:Rv0116c; -.
DR KEGG; mtv:RVBD_0116c; -.
DR TubercuList; Rv0116c; -.
DR eggNOG; COG1376; Bacteria.
DR OMA; FMTEFRT; -.
DR PhylomeDB; O53638; -.
DR BioCyc; MetaCyc:G185E-4233-MON; -.
DR UniPathway; UPA00219; -.
DR Proteomes; UP000001584; Chromosome.
DR GO; GO:0005576; C:extracellular region; HDA:MTBBASE.
DR GO; GO:0042597; C:periplasmic space; IEA:UniProtKB-SubCell.
DR GO; GO:0016746; F:acyltransferase activity; 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:0018104; P:peptidoglycan-protein cross-linking; 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.
PE 1: Evidence at protein level;
KW 3D-structure; Acyltransferase; Cell shape;
KW Cell wall biogenesis/degradation; Peptidoglycan synthesis; Periplasm;
KW Reference proteome; Signal; Transferase.
FT SIGNAL 1..28
FT /evidence="ECO:0000255"
FT CHAIN 29..251
FT /note="L,D-transpeptidase 1"
FT /id="PRO_0000430332"
FT DOMAIN 129..249
FT /note="YkuD"
FT ACT_SITE 208
FT /note="Proton donor/acceptor"
FT /evidence="ECO:0000305|PubMed:23999293"
FT ACT_SITE 226
FT /note="Nucleophile"
FT /evidence="ECO:0000269|PubMed:23999293"
FT BINDING 190
FT /ligand="substrate"
FT /evidence="ECO:0000250"
FT BINDING 203..204
FT /ligand="substrate"
FT /evidence="ECO:0000250"
FT BINDING 208
FT /ligand="imipenem"
FT /ligand_id="ChEBI:CHEBI:190509"
FT /ligand_note="inhibitor"
FT /evidence="ECO:0000269|Ref.2, ECO:0007744|PDB:4JMX"
FT BINDING 224
FT /ligand="imipenem"
FT /ligand_id="ChEBI:CHEBI:190509"
FT /ligand_note="inhibitor"
FT /evidence="ECO:0000269|Ref.2, ECO:0007744|PDB:4JMX"
FT BINDING 226
FT /ligand="imipenem"
FT /ligand_id="ChEBI:CHEBI:190509"
FT /ligand_note="inhibitor"
FT /note="covalent"
FT /evidence="ECO:0000269|Ref.2, ECO:0007744|PDB:4JMX"
FT BINDING 228
FT /ligand="imipenem"
FT /ligand_id="ChEBI:CHEBI:190509"
FT /ligand_note="inhibitor"
FT /evidence="ECO:0000269|Ref.2, ECO:0007744|PDB:4JMX"
FT BINDING 228
FT /ligand="substrate"
FT /evidence="ECO:0000250"
FT STRAND 39..41
FT /evidence="ECO:0007829|PDB:5E5L"
FT STRAND 56..58
FT /evidence="ECO:0007829|PDB:5E5L"
FT HELIX 67..72
FT /evidence="ECO:0007829|PDB:5E5L"
FT STRAND 74..77
FT /evidence="ECO:0007829|PDB:5E5L"
FT STRAND 84..87
FT /evidence="ECO:0007829|PDB:5E5L"
FT STRAND 94..100
FT /evidence="ECO:0007829|PDB:5E5L"
FT STRAND 107..112
FT /evidence="ECO:0007829|PDB:5E5L"
FT STRAND 115..121
FT /evidence="ECO:0007829|PDB:5E5L"
FT STRAND 125..130
FT /evidence="ECO:0007829|PDB:5E5L"
FT TURN 131..134
FT /evidence="ECO:0007829|PDB:5E5L"
FT STRAND 135..149
FT /evidence="ECO:0007829|PDB:5E5L"
FT STRAND 151..154
FT /evidence="ECO:0007829|PDB:5E5L"
FT STRAND 162..165
FT /evidence="ECO:0007829|PDB:5E5L"
FT STRAND 168..176
FT /evidence="ECO:0007829|PDB:5E5L"
FT HELIX 177..180
FT /evidence="ECO:0007829|PDB:5E5L"
FT STRAND 184..186
FT /evidence="ECO:0007829|PDB:4JMX"
FT STRAND 191..199
FT /evidence="ECO:0007829|PDB:5E5L"
FT STRAND 206..209
FT /evidence="ECO:0007829|PDB:5E5L"
FT HELIX 211..213
FT /evidence="ECO:0007829|PDB:4JMN"
FT TURN 214..219
FT /evidence="ECO:0007829|PDB:4JMN"
FT STRAND 223..229
FT /evidence="ECO:0007829|PDB:4JMN"
FT HELIX 231..240
FT /evidence="ECO:0007829|PDB:5E5L"
FT STRAND 246..250
FT /evidence="ECO:0007829|PDB:5E5L"
SQ SEQUENCE 251 AA; 26916 MW; E074256B6445EABC CRC64;
MRRVVRYLSV VVAITLMLTA ESVSIATAAV PPLQPIPGVA SVSPANGAVV GVAHPVVVTF
TTPVTDRRAV ERSIRISTPH NTTGHFEWVA SNVVRWVPHR YWPPHTRVSV GVQELTEGFE
TGDALIGVAS ISAHTFTVSR NGEVLRTMPA SLGKPSRPTP IGSFHAMSKE RTVVMDSRTI
GIPLNSSDGY LLTAHYAVRV TWSGVYVHSA PWSVNSQGYA NVSHGCINLS PDNAAWYFDA
VTVGDPIEVV G
