MURE_STAA8
ID MURE_STAA8 Reviewed; 493 AA.
AC Q2FZP6;
DT 15-JAN-2008, integrated into UniProtKB/Swiss-Prot.
DT 21-MAR-2006, sequence version 1.
DT 03-AUG-2022, entry version 103.
DE RecName: Full=UDP-N-acetylmuramoyl-L-alanyl-D-glutamate--L-lysine ligase;
DE EC=6.3.2.7 {ECO:0000269|PubMed:14114846};
DE AltName: Full=L-lysine-adding enzyme;
DE AltName: Full=UDP-MurNAc-L-Ala-D-Glu:L-Lys ligase;
DE AltName: Full=UDP-MurNAc-tripeptide synthetase;
DE AltName: Full=UDP-N-acetylmuramyl-tripeptide synthetase;
GN Name=murE; OrderedLocusNames=SAOUHSC_00954;
OS Staphylococcus aureus (strain NCTC 8325 / PS 47).
OC Bacteria; Firmicutes; Bacilli; Bacillales; Staphylococcaceae;
OC Staphylococcus.
OX NCBI_TaxID=93061;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=NCTC 8325 / PS 47;
RA Gillaspy A.F., Worrell V., Orvis J., Roe B.A., Dyer D.W., Iandolo J.J.;
RT "The Staphylococcus aureus NCTC 8325 genome.";
RL (In) Fischetti V., Novick R., Ferretti J., Portnoy D., Rood J. (eds.);
RL Gram positive pathogens, 2nd edition, pp.381-412, ASM Press, Washington
RL D.C. (2006).
RN [2]
RP FUNCTION, CHARACTERIZATION, CATALYTIC ACTIVITY, SUBSTRATE SPECIFICITY, AND
RP BIOPHYSICOCHEMICAL PROPERTIES.
RC STRAIN=Copenhagen;
RX PubMed=14114846;
RA Ito E., Strominger J.L.;
RT "Enzymatic synthesis of the peptide in bacterial uridine nucleotides. III.
RT Purification and properties of L-lysine-adding enzyme.";
RL J. Biol. Chem. 239:210-214(1964).
RN [3]
RP FUNCTION.
RX PubMed=10498701; DOI=10.1128/jb.181.19.5909-5914.1999;
RA Mengin-Lecreulx D., Falla T., Blanot D., van Heijenoort J., Adams D.J.,
RA Chopra I.;
RT "Expression of the Staphylococcus aureus UDP-N-acetylmuramoyl-L-alanyl-D-
RT glutamate:L-lysine ligase in Escherichia coli and effects on peptidoglycan
RT biosynthesis and cell growth.";
RL J. Bacteriol. 181:5909-5914(1999).
RN [4]
RP ROLE IN ANTIBIOTIC RESISTANCE.
RX PubMed=14996801; DOI=10.1128/jb.186.6.1705-1713.2004;
RA Gardete S., Ludovice A.M., Sobral R.G., Filipe S.R., de Lencastre H.,
RA Tomasz A.;
RT "Role of murE in the expression of beta-lactam antibiotic resistance in
RT Staphylococcus aureus.";
RL J. Bacteriol. 186:1705-1713(2004).
CC -!- FUNCTION: Catalyzes the addition of L-lysine to the nucleotide
CC precursor UDP-N-acetylmuramoyl-L-alanyl-D-glutamate (UMAG) in the
CC biosynthesis of bacterial cell-wall peptidoglycan. Cannot use
CC diaminopimelate as substrate. Seems to have a role in beta-lactam
CC antibiotic resistance. {ECO:0000269|PubMed:10498701,
CC ECO:0000269|PubMed:14114846, ECO:0000269|PubMed:14996801}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=ATP + L-lysine + UDP-N-acetyl-alpha-D-muramoyl-L-alanyl-D-
CC glutamate = ADP + H(+) + phosphate + UDP-N-acetyl-alpha-D-muramoyl-L-
CC alanyl-gamma-D-glutamyl-L-lysine; Xref=Rhea:RHEA:17969,
CC ChEBI:CHEBI:15378, ChEBI:CHEBI:30616, ChEBI:CHEBI:32551,
CC ChEBI:CHEBI:43474, ChEBI:CHEBI:83900, ChEBI:CHEBI:83903,
CC ChEBI:CHEBI:456216; EC=6.3.2.7;
CC Evidence={ECO:0000269|PubMed:14114846};
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=0.4 mM for UDP-N-acetylmuramoyl-L-Ala-D-Glu
CC {ECO:0000269|PubMed:14114846};
CC KM=0.5 mM for L-lysine {ECO:0000269|PubMed:14114846};
CC KM=0.3 mM for ATP {ECO:0000269|PubMed:14114846};
CC pH dependence:
CC Optimum pH is 8.4-9. {ECO:0000269|PubMed:14114846};
CC -!- PATHWAY: Cell wall biogenesis; peptidoglycan biosynthesis.
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000250}.
CC -!- PTM: Carboxylation is probably crucial for Mg(2+) binding and,
CC consequently, for the gamma-phosphate positioning of ATP.
CC {ECO:0000250}.
CC -!- MISCELLANEOUS: Expression of this protein in E.coli results in 50%
CC incorporation of L-Lys into the peptidoglycan (which normally contains
CC meso-diaminopimelate instead), leading to abnormal morphological
CC changes and subsequent cell lysis.
CC -!- SIMILARITY: Belongs to the MurCDEF family. MurE subfamily.
CC {ECO:0000305}.
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DR EMBL; CP000253; ABD30079.1; -; Genomic_DNA.
DR RefSeq; WP_000340118.1; NZ_LS483365.1.
DR RefSeq; YP_499507.1; NC_007795.1.
DR PDB; 4C12; X-ray; 1.80 A; A=1-493.
DR PDB; 4C13; X-ray; 1.90 A; A=1-493.
DR PDBsum; 4C12; -.
DR PDBsum; 4C13; -.
DR AlphaFoldDB; Q2FZP6; -.
DR SMR; Q2FZP6; -.
DR STRING; 1280.SAXN108_1015; -.
DR BindingDB; Q2FZP6; -.
DR PRIDE; Q2FZP6; -.
DR EnsemblBacteria; ABD30079; ABD30079; SAOUHSC_00954.
DR GeneID; 3920665; -.
DR KEGG; sao:SAOUHSC_00954; -.
DR PATRIC; fig|93061.5.peg.876; -.
DR eggNOG; COG0769; Bacteria.
DR HOGENOM; CLU_022291_0_1_9; -.
DR OMA; CFMEVSS; -.
DR BRENDA; 6.3.2.7; 3352.
DR UniPathway; UPA00219; -.
DR Proteomes; UP000008816; Chromosome.
DR GO; GO:0005737; C:cytoplasm; IEA:UniProtKB-SubCell.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-UniRule.
DR GO; GO:0000287; F:magnesium ion binding; IEA:UniProtKB-UniRule.
DR GO; GO:0047482; F:UDP-N-acetylmuramoyl-L-alanyl-D-glutamate-L-lysine ligase activity; IEA:UniProtKB-UniRule.
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; IEA:UniProtKB-UniRule.
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; Nucleotide-binding;
KW Peptidoglycan synthesis; Reference proteome.
FT CHAIN 1..493
FT /note="UDP-N-acetylmuramoyl-L-alanyl-D-glutamate--L-lysine
FT ligase"
FT /id="PRO_1000012382"
FT MOTIF 406..409
FT /note="L-lysine recognition motif"
FT BINDING 30
FT /ligand="UDP-N-acetyl-alpha-D-muramoyl-L-alanyl-D-
FT glutamate"
FT /ligand_id="ChEBI:CHEBI:83900"
FT /evidence="ECO:0000250"
FT BINDING 110..116
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255"
FT BINDING 152..153
FT /ligand="UDP-N-acetyl-alpha-D-muramoyl-L-alanyl-D-
FT glutamate"
FT /ligand_id="ChEBI:CHEBI:83900"
FT /evidence="ECO:0000250"
FT BINDING 179
FT /ligand="UDP-N-acetyl-alpha-D-muramoyl-L-alanyl-D-
FT glutamate"
FT /ligand_id="ChEBI:CHEBI:83900"
FT /evidence="ECO:0000250"
FT BINDING 187
FT /ligand="UDP-N-acetyl-alpha-D-muramoyl-L-alanyl-D-
FT glutamate"
FT /ligand_id="ChEBI:CHEBI:83900"
FT /evidence="ECO:0000250"
FT MOD_RES 219
FT /note="N6-carboxylysine"
FT /evidence="ECO:0000250"
FT HELIX 3..7
FT /evidence="ECO:0007829|PDB:4C12"
FT STRAND 14..17
FT /evidence="ECO:0007829|PDB:4C12"
FT STRAND 25..28
FT /evidence="ECO:0007829|PDB:4C12"
FT HELIX 30..32
FT /evidence="ECO:0007829|PDB:4C12"
FT STRAND 37..40
FT /evidence="ECO:0007829|PDB:4C12"
FT HELIX 49..52
FT /evidence="ECO:0007829|PDB:4C12"
FT HELIX 53..58
FT /evidence="ECO:0007829|PDB:4C12"
FT STRAND 63..68
FT /evidence="ECO:0007829|PDB:4C12"
FT STRAND 76..80
FT /evidence="ECO:0007829|PDB:4C12"
FT HELIX 84..95
FT /evidence="ECO:0007829|PDB:4C12"
FT HELIX 99..101
FT /evidence="ECO:0007829|PDB:4C12"
FT STRAND 102..112
FT /evidence="ECO:0007829|PDB:4C12"
FT HELIX 114..127
FT /evidence="ECO:0007829|PDB:4C12"
FT STRAND 132..136
FT /evidence="ECO:0007829|PDB:4C12"
FT STRAND 139..142
FT /evidence="ECO:0007829|PDB:4C12"
FT STRAND 145..147
FT /evidence="ECO:0007829|PDB:4C12"
FT HELIX 156..168
FT /evidence="ECO:0007829|PDB:4C12"
FT STRAND 172..177
FT /evidence="ECO:0007829|PDB:4C12"
FT HELIX 180..184
FT /evidence="ECO:0007829|PDB:4C12"
FT TURN 185..190
FT /evidence="ECO:0007829|PDB:4C12"
FT STRAND 194..198
FT /evidence="ECO:0007829|PDB:4C12"
FT HELIX 206..209
FT /evidence="ECO:0007829|PDB:4C12"
FT HELIX 212..224
FT /evidence="ECO:0007829|PDB:4C12"
FT STRAND 235..239
FT /evidence="ECO:0007829|PDB:4C12"
FT HELIX 245..249
FT /evidence="ECO:0007829|PDB:4C12"
FT STRAND 254..263
FT /evidence="ECO:0007829|PDB:4C12"
FT STRAND 266..275
FT /evidence="ECO:0007829|PDB:4C12"
FT STRAND 278..285
FT /evidence="ECO:0007829|PDB:4C12"
FT STRAND 288..296
FT /evidence="ECO:0007829|PDB:4C12"
FT HELIX 299..314
FT /evidence="ECO:0007829|PDB:4C12"
FT HELIX 319..326
FT /evidence="ECO:0007829|PDB:4C12"
FT STRAND 335..338
FT /evidence="ECO:0007829|PDB:4C12"
FT STRAND 343..350
FT /evidence="ECO:0007829|PDB:4C12"
FT HELIX 355..365
FT /evidence="ECO:0007829|PDB:4C12"
FT HELIX 366..368
FT /evidence="ECO:0007829|PDB:4C12"
FT STRAND 373..380
FT /evidence="ECO:0007829|PDB:4C12"
FT HELIX 388..395
FT /evidence="ECO:0007829|PDB:4C12"
FT STRAND 398..407
FT /evidence="ECO:0007829|PDB:4C12"
FT HELIX 413..421
FT /evidence="ECO:0007829|PDB:4C12"
FT STRAND 425..427
FT /evidence="ECO:0007829|PDB:4C12"
FT STRAND 429..431
FT /evidence="ECO:0007829|PDB:4C12"
FT HELIX 435..445
FT /evidence="ECO:0007829|PDB:4C12"
FT STRAND 451..456
FT /evidence="ECO:0007829|PDB:4C12"
FT STRAND 462..465
FT /evidence="ECO:0007829|PDB:4C12"
FT HELIX 466..468
FT /evidence="ECO:0007829|PDB:4C12"
FT STRAND 469..472
FT /evidence="ECO:0007829|PDB:4C12"
FT HELIX 475..487
FT /evidence="ECO:0007829|PDB:4C12"
SQ SEQUENCE 493 AA; 54105 MW; 0D224B23DA5A1390 CRC64;
MDASTLFKKV KVKRVLGSLE QQIDDITTDS RTAREGSIFV ASVGYTVDSH KFCQNVADQG
CKLVVVNKEQ SLPANVTQVV VPDTLRVASI LAHTLYDYPS HQLVTFGVTG TNGKTSIATM
IHLIQRKLQK NSAYLGTNGF QINETKTKGA NTTPETVSLT KKIKEAVDAG AESMTLEVSS
HGLVLGRLRG VEFDVAIFSN LTQDHLDFHG TMEAYGHAKS LLFSQLGEDL SKEKYVVLNN
DDSFSEYLRT VTPYEVFSYG IDEEAQFMAK NIQESLQGVS FDFVTPFGTY PVKSPYVGKF
NISNIMAAMI AVWSKGTSLE TIIKAVENLE PVEGRLEVLD PSLPIDLIID YAHTADGMNK
LIDAVQPFVK QKLIFLVGMA GERDLTKTPE MGRVACRADY VIFTPDNPAN DDPKMLTAEL
AKGATHQNYI EFDDRAEGIK HAIDIAEPGD TVVLASKGRE PYQIMPGHIK VPHRDDLIGL
EAAYKKFGGG PVD
