MURE_MYCTU
ID MURE_MYCTU Reviewed; 535 AA.
AC P9WJL3; L0T8S9; O06219; P65477;
DT 16-APR-2014, integrated into UniProtKB/Swiss-Prot.
DT 16-APR-2014, sequence version 1.
DT 03-AUG-2022, entry version 45.
DE RecName: Full=UDP-N-acetylmuramoyl-L-alanyl-D-glutamate--2,6-diaminopimelate ligase {ECO:0000255|HAMAP-Rule:MF_00208};
DE EC=6.3.2.13 {ECO:0000255|HAMAP-Rule:MF_00208};
DE AltName: Full=Meso-A2pm-adding enzyme {ECO:0000255|HAMAP-Rule:MF_00208};
DE AltName: Full=Meso-diaminopimelate-adding enzyme {ECO:0000255|HAMAP-Rule:MF_00208};
DE AltName: Full=UDP-MurNAc-L-Ala-D-Glu:meso-diaminopimelate ligase {ECO:0000255|HAMAP-Rule:MF_00208};
DE AltName: Full=UDP-MurNAc-tripeptide synthetase {ECO:0000255|HAMAP-Rule:MF_00208};
DE AltName: Full=UDP-N-acetylmuramyl-tripeptide synthetase {ECO:0000255|HAMAP-Rule:MF_00208};
GN Name=murE {ECO:0000255|HAMAP-Rule:MF_00208}; OrderedLocusNames=Rv2158c;
GN ORFNames=MTCY270.10;
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 AS A DRUG TARGET [LARGE SCALE ANALYSIS].
RX PubMed=19099550; DOI=10.1186/1752-0509-2-109;
RA Raman K., Yeturu K., Chandra N.;
RT "targetTB: a target identification pipeline for Mycobacterium tuberculosis
RT through an interactome, reactome and genome-scale structural analysis.";
RL BMC Syst. Biol. 2:109-109(2008).
RN [3]
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).
CC -!- FUNCTION: Catalyzes the addition of meso-diaminopimelic acid to the
CC nucleotide precursor UDP-N-acetylmuramoyl-L-alanyl-D-glutamate (UMAG)
CC in the biosynthesis of bacterial cell-wall peptidoglycan.
CC {ECO:0000255|HAMAP-Rule:MF_00208}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=ATP + meso-2,6-diaminoheptanedioate + UDP-N-acetyl-alpha-D-
CC muramoyl-L-alanyl-D-glutamate = ADP + H(+) + phosphate + UDP-N-
CC acetyl-alpha-D-muramoyl-L-alanyl-gamma-D-glutamyl-meso-2,6-
CC diaminoheptanedioate; Xref=Rhea:RHEA:23676, ChEBI:CHEBI:15378,
CC ChEBI:CHEBI:30616, ChEBI:CHEBI:43474, ChEBI:CHEBI:57791,
CC ChEBI:CHEBI:83900, ChEBI:CHEBI:83905, ChEBI:CHEBI:456216;
CC EC=6.3.2.13; Evidence={ECO:0000255|HAMAP-Rule:MF_00208};
CC -!- COFACTOR:
CC Name=Mg(2+); Xref=ChEBI:CHEBI:18420;
CC Evidence={ECO:0000255|HAMAP-Rule:MF_00208};
CC -!- PATHWAY: Cell wall biogenesis; peptidoglycan biosynthesis.
CC {ECO:0000255|HAMAP-Rule:MF_00208}.
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000255|HAMAP-Rule:MF_00208}.
CC -!- PTM: Carboxylation is probably crucial for Mg(2+) binding and,
CC consequently, for the gamma-phosphate positioning of ATP.
CC {ECO:0000255|HAMAP-Rule:MF_00208}.
CC -!- MISCELLANEOUS: Was identified as a high-confidence drug target.
CC -!- SIMILARITY: Belongs to the MurCDEF family. MurE subfamily.
CC {ECO:0000255|HAMAP-Rule:MF_00208}.
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DR EMBL; AL123456; CCP44934.1; -; Genomic_DNA.
DR PIR; B70580; B70580.
DR RefSeq; NP_216674.1; NC_000962.3.
DR RefSeq; WP_003411189.1; NZ_NVQJ01000044.1.
DR PDB; 2WTZ; X-ray; 3.00 A; A/B/C/D=1-535.
DR PDB; 2XJA; X-ray; 3.00 A; A/B/C/D=1-535.
DR PDBsum; 2WTZ; -.
DR PDBsum; 2XJA; -.
DR AlphaFoldDB; P9WJL3; -.
DR SMR; P9WJL3; -.
DR STRING; 83332.Rv2158c; -.
DR BindingDB; P9WJL3; -.
DR PaxDb; P9WJL3; -.
DR DNASU; 887252; -.
DR GeneID; 887252; -.
DR KEGG; mtu:Rv2158c; -.
DR PATRIC; fig|83332.111.peg.2404; -.
DR TubercuList; Rv2158c; -.
DR eggNOG; COG0769; Bacteria.
DR OMA; CFMEVSS; -.
DR PhylomeDB; P9WJL3; -.
DR BioCyc; MetaCyc:G185E-6366-MON; -.
DR BRENDA; 6.3.2.13; 3445.
DR SABIO-RK; P9WJL3; -.
DR UniPathway; UPA00219; -.
DR Proteomes; UP000001584; Chromosome.
DR GO; GO:0005829; C:cytosol; HDA:MTBBASE.
DR GO; GO:0005886; C:plasma membrane; HDA:MTBBASE.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-UniRule.
DR GO; GO:0000287; F:magnesium ion binding; IEA:UniProtKB-UniRule.
DR GO; GO:0008765; F:UDP-N-acetylmuramoylalanyl-D-glutamate-2,6-diaminopimelate ligase activity; IDA:MTBBASE.
DR GO; GO:0007049; P:cell cycle; IEA:UniProtKB-KW.
DR GO; GO:0051301; P:cell division; IEA:UniProtKB-KW.
DR GO; GO:0071555; P:cell wall organization; IEA:UniProtKB-KW.
DR GO; GO:0009252; P:peptidoglycan biosynthetic process; IDA:MTBBASE.
DR GO; GO:0008360; P:regulation of cell shape; IEA:UniProtKB-KW.
DR Gene3D; 3.40.1190.10; -; 1.
DR Gene3D; 3.90.190.20; -; 1.
DR HAMAP; MF_00208; MurE; 1.
DR InterPro; IPR036565; Mur-like_cat_sf.
DR InterPro; IPR004101; Mur_ligase_C.
DR InterPro; IPR036615; Mur_ligase_C_dom_sf.
DR InterPro; IPR013221; Mur_ligase_cen.
DR InterPro; IPR000713; Mur_ligase_N.
DR InterPro; IPR035911; MurE/MurF_N.
DR InterPro; IPR005761; UDP-N-AcMur-Glu-dNH2Pim_ligase.
DR Pfam; PF01225; Mur_ligase; 1.
DR Pfam; PF02875; Mur_ligase_C; 1.
DR Pfam; PF08245; Mur_ligase_M; 1.
DR SUPFAM; SSF53244; SSF53244; 1.
DR SUPFAM; SSF53623; SSF53623; 1.
DR SUPFAM; SSF63418; SSF63418; 1.
DR TIGRFAMs; TIGR01085; murE; 1.
PE 1: Evidence at protein level;
KW 3D-structure; ATP-binding; Cell cycle; Cell division; Cell shape;
KW Cell wall biogenesis/degradation; Cytoplasm; Ligase; Magnesium;
KW Nucleotide-binding; Peptidoglycan synthesis; Reference proteome.
FT CHAIN 1..535
FT /note="UDP-N-acetylmuramoyl-L-alanyl-D-glutamate--2,6-
FT diaminopimelate ligase"
FT /id="PRO_0000101913"
FT MOTIF 448..451
FT /note="Meso-diaminopimelate recognition motif"
FT BINDING 67
FT /ligand="UDP-N-acetyl-alpha-D-muramoyl-L-alanyl-D-
FT glutamate"
FT /ligand_id="ChEBI:CHEBI:83900"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_00208"
FT BINDING 153..159
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_00208"
FT BINDING 195..196
FT /ligand="UDP-N-acetyl-alpha-D-muramoyl-L-alanyl-D-
FT glutamate"
FT /ligand_id="ChEBI:CHEBI:83900"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_00208"
FT BINDING 222
FT /ligand="UDP-N-acetyl-alpha-D-muramoyl-L-alanyl-D-
FT glutamate"
FT /ligand_id="ChEBI:CHEBI:83900"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_00208"
FT BINDING 230
FT /ligand="UDP-N-acetyl-alpha-D-muramoyl-L-alanyl-D-
FT glutamate"
FT /ligand_id="ChEBI:CHEBI:83900"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_00208"
FT BINDING 424
FT /ligand="meso-2,6-diaminoheptanedioate"
FT /ligand_id="ChEBI:CHEBI:57791"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_00208"
FT BINDING 448..451
FT /ligand="meso-2,6-diaminoheptanedioate"
FT /ligand_id="ChEBI:CHEBI:57791"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_00208"
FT BINDING 502
FT /ligand="meso-2,6-diaminoheptanedioate"
FT /ligand_id="ChEBI:CHEBI:57791"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_00208"
FT BINDING 506
FT /ligand="meso-2,6-diaminoheptanedioate"
FT /ligand_id="ChEBI:CHEBI:57791"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_00208"
FT MOD_RES 262
FT /note="N6-carboxylysine"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_00208"
FT HELIX 36..43
FT /evidence="ECO:0007829|PDB:2WTZ"
FT STRAND 46..49
FT /evidence="ECO:0007829|PDB:2WTZ"
FT TURN 57..59
FT /evidence="ECO:0007829|PDB:2WTZ"
FT STRAND 64..67
FT /evidence="ECO:0007829|PDB:2WTZ"
FT HELIX 69..71
FT /evidence="ECO:0007829|PDB:2WTZ"
FT STRAND 76..80
FT /evidence="ECO:0007829|PDB:2WTZ"
FT HELIX 88..91
FT /evidence="ECO:0007829|PDB:2WTZ"
FT HELIX 92..97
FT /evidence="ECO:0007829|PDB:2WTZ"
FT STRAND 102..105
FT /evidence="ECO:0007829|PDB:2WTZ"
FT HELIX 107..113
FT /evidence="ECO:0007829|PDB:2WTZ"
FT STRAND 121..123
FT /evidence="ECO:0007829|PDB:2WTZ"
FT STRAND 125..127
FT /evidence="ECO:0007829|PDB:2WTZ"
FT HELIX 128..138
FT /evidence="ECO:0007829|PDB:2WTZ"
FT HELIX 142..144
FT /evidence="ECO:0007829|PDB:2WTZ"
FT STRAND 145..155
FT /evidence="ECO:0007829|PDB:2WTZ"
FT HELIX 157..170
FT /evidence="ECO:0007829|PDB:2WTZ"
FT STRAND 175..181
FT /evidence="ECO:0007829|PDB:2WTZ"
FT STRAND 183..185
FT /evidence="ECO:0007829|PDB:2WTZ"
FT STRAND 188..190
FT /evidence="ECO:0007829|PDB:2WTZ"
FT STRAND 193..196
FT /evidence="ECO:0007829|PDB:2WTZ"
FT HELIX 199..211
FT /evidence="ECO:0007829|PDB:2WTZ"
FT STRAND 216..220
FT /evidence="ECO:0007829|PDB:2WTZ"
FT HELIX 223..227
FT /evidence="ECO:0007829|PDB:2WTZ"
FT TURN 228..233
FT /evidence="ECO:0007829|PDB:2WTZ"
FT STRAND 236..241
FT /evidence="ECO:0007829|PDB:2WTZ"
FT TURN 249..251
FT /evidence="ECO:0007829|PDB:2WTZ"
FT STRAND 252..254
FT /evidence="ECO:0007829|PDB:2WTZ"
FT HELIX 255..263
FT /evidence="ECO:0007829|PDB:2WTZ"
FT TURN 264..266
FT /evidence="ECO:0007829|PDB:2WTZ"
FT STRAND 275..280
FT /evidence="ECO:0007829|PDB:2WTZ"
FT HELIX 284..293
FT /evidence="ECO:0007829|PDB:2WTZ"
FT STRAND 297..304
FT /evidence="ECO:0007829|PDB:2WTZ"
FT STRAND 307..316
FT /evidence="ECO:0007829|PDB:2WTZ"
FT TURN 317..319
FT /evidence="ECO:0007829|PDB:2WTZ"
FT STRAND 320..326
FT /evidence="ECO:0007829|PDB:2WTZ"
FT STRAND 332..338
FT /evidence="ECO:0007829|PDB:2WTZ"
FT HELIX 342..357
FT /evidence="ECO:0007829|PDB:2WTZ"
FT HELIX 362..369
FT /evidence="ECO:0007829|PDB:2WTZ"
FT STRAND 377..380
FT /evidence="ECO:0007829|PDB:2WTZ"
FT STRAND 386..392
FT /evidence="ECO:0007829|PDB:2WTZ"
FT HELIX 397..405
FT /evidence="ECO:0007829|PDB:2WTZ"
FT STRAND 410..412
FT /evidence="ECO:0007829|PDB:2WTZ"
FT STRAND 414..418
FT /evidence="ECO:0007829|PDB:2WTZ"
FT HELIX 426..428
FT /evidence="ECO:0007829|PDB:2WTZ"
FT HELIX 429..439
FT /evidence="ECO:0007829|PDB:2WTZ"
FT STRAND 441..445
FT /evidence="ECO:0007829|PDB:2WTZ"
FT HELIX 455..466
FT /evidence="ECO:0007829|PDB:2WTZ"
FT STRAND 474..477
FT /evidence="ECO:0007829|PDB:2WTZ"
FT HELIX 481..491
FT /evidence="ECO:0007829|PDB:2WTZ"
FT STRAND 497..502
FT /evidence="ECO:0007829|PDB:2WTZ"
FT HELIX 522..529
FT /evidence="ECO:0007829|PDB:2WTZ"
SQ SEQUENCE 535 AA; 55341 MW; 4EB7D79C6374817E CRC64;
MSSLARGISR RRTEVATQVE AAPTGLRPNA VVGVRLAALA DQVGAALAEG PAQRAVTEDR
TVTGVTLRAQ DVSPGDLFAA LTGSTTHGAR HVGDAIARGA VAVLTDPAGV AEIAGRAAVP
VLVHPAPRGV LGGLAATVYG HPSERLTVIG ITGTSGKTTT TYLVEAGLRA AGRVAGLIGT
IGIRVGGADL PSALTTPEAP TLQAMLAAMV ERGVDTVVME VSSHALALGR VDGTRFAVGA
FTNLSRDHLD FHPSMADYFE AKASLFDPDS ALRARTAVVC IDDDAGRAMA ARAADAITVS
AADRPAHWRA TDVAPTDAGG QQFTAIDPAG VGHHIGIRLP GRYNVANCLV ALAILDTVGV
SPEQAVPGLR EIRVPGRLEQ IDRGQGFLAL VDYAHKPEAL RSVLTTLAHP DRRLAVVFGA
GGDRDPGKRA PMGRIAAQLA DLVVVTDDNP RDEDPTAIRR EILAGAAEVG GDAQVVEIAD
RRDAIRHAVA WARPGDVVLI AGKGHETGQR GGGRVRPFDD RVELAAALEA LERRA
