MRAY_AQUAE
ID MRAY_AQUAE Reviewed; 359 AA.
AC O66465;
DT 30-MAY-2000, integrated into UniProtKB/Swiss-Prot.
DT 01-AUG-1998, sequence version 1.
DT 03-AUG-2022, entry version 143.
DE RecName: Full=Phospho-N-acetylmuramoyl-pentapeptide-transferase {ECO:0000255|HAMAP-Rule:MF_00038};
DE EC=2.7.8.13 {ECO:0000255|HAMAP-Rule:MF_00038, ECO:0000269|PubMed:23990562, ECO:0000269|PubMed:27088606, ECO:0000269|PubMed:29459785};
DE AltName: Full=UDP-MurNAc-pentapeptide phosphotransferase {ECO:0000255|HAMAP-Rule:MF_00038};
GN Name=mraY {ECO:0000255|HAMAP-Rule:MF_00038}; OrderedLocusNames=aq_053;
OS Aquifex aeolicus (strain VF5).
OC Bacteria; Aquificae; Aquificales; Aquificaceae; Aquifex.
OX NCBI_TaxID=224324;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=VF5;
RX PubMed=9537320; DOI=10.1038/32831;
RA Deckert G., Warren P.V., Gaasterland T., Young W.G., Lenox A.L.,
RA Graham D.E., Overbeek R., Snead M.A., Keller M., Aujay M., Huber R.,
RA Feldman R.A., Short J.M., Olsen G.J., Swanson R.V.;
RT "The complete genome of the hyperthermophilic bacterium Aquifex aeolicus.";
RL Nature 392:353-358(1998).
RN [2]
RP FUNCTION, ACTIVITY REGULATION, COFACTOR, CATALYTIC ACTIVITY, AND
RP MUTAGENESIS OF ASP-265.
RX PubMed=29459785; DOI=10.1038/s41594-018-0031-y;
RA Yoo J., Mashalidis E.H., Kuk A.C.Y., Yamamoto K., Kaeser B., Ichikawa S.,
RA Lee S.Y.;
RT "GlcNAc-1-P-transferase-tunicamycin complex structure reveals basis for
RT inhibition of N-glycosylation.";
RL Nat. Struct. Mol. Biol. 25:217-224(2018).
RN [3] {ECO:0007744|PDB:4J72}
RP X-RAY CRYSTALLOGRAPHY (3.30 ANGSTROMS), FUNCTION, SUBUNIT, TOPOLOGY,
RP ACTIVITY REGULATION, MUTAGENESIS OF ASP-117; ASP-118; ASP-265; HIS-324;
RP HIS-325 AND HIS-326, COFACTOR, AND CATALYTIC ACTIVITY.
RX PubMed=23990562; DOI=10.1126/science.1236501;
RA Chung B.C., Zhao J., Gillespie R.A., Kwon D.Y., Guan Z., Hong J., Zhou P.,
RA Lee S.Y.;
RT "Crystal structure of MraY, an essential membrane enzyme for bacterial cell
RT wall synthesis.";
RL Science 341:1012-1016(2013).
RN [4] {ECO:0007744|PDB:5CKR}
RP X-RAY CRYSTALLOGRAPHY (2.95 ANGSTROMS) IN COMPLEX WITH MURAYMYCIN D2
RP INHIBITOR, FUNCTION, COFACTOR, CATALYTIC ACTIVITY, ACTIVITY REGULATION,
RP BIOPHYSICOCHEMICAL PROPERTIES, AND MUTAGENESIS OF LYS-70; ASN-190; ASP-193;
RP ASP-196; PHE-262 AND GLN-305.
RX PubMed=27088606; DOI=10.1038/nature17636;
RA Chung B.C., Mashalidis E.H., Tanino T., Kim M., Matsuda A., Hong J.,
RA Ichikawa S., Lee S.Y.;
RT "Structural insights into inhibition of lipid I production in bacterial
RT cell wall synthesis.";
RL Nature 533:557-560(2016).
CC -!- FUNCTION: Catalyzes the initial step of the lipid cycle reactions in
CC the biosynthesis of the cell wall peptidoglycan: transfers
CC peptidoglycan precursor phospho-MurNAc-pentapeptide from UDP-MurNAc-
CC pentapeptide onto the lipid carrier undecaprenyl phosphate, yielding
CC undecaprenyl-pyrophosphoryl-MurNAc-pentapeptide, known as lipid I.
CC {ECO:0000255|HAMAP-Rule:MF_00038, ECO:0000269|PubMed:23990562,
CC ECO:0000269|PubMed:27088606, ECO:0000269|PubMed:29459785}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=di-trans,octa-cis-undecaprenyl phosphate + UDP-N-acetyl-alpha-
CC D-muramoyl-L-alanyl-gamma-D-glutamyl-meso-2,6-diaminopimeloyl-D-
CC alanyl-D-alanine = di-trans-octa-cis-undecaprenyl diphospho-N-acetyl-
CC alpha-D-muramoyl-L-alanyl-D-glutamyl-meso-2,6-diaminopimeloyl-D-
CC alanyl-D-alanine + UMP; Xref=Rhea:RHEA:28386, ChEBI:CHEBI:57865,
CC ChEBI:CHEBI:60392, ChEBI:CHEBI:61386, ChEBI:CHEBI:61387; EC=2.7.8.13;
CC Evidence={ECO:0000255|HAMAP-Rule:MF_00038,
CC ECO:0000269|PubMed:23990562, ECO:0000269|PubMed:27088606,
CC ECO:0000269|PubMed:29459785};
CC -!- COFACTOR:
CC Name=Mg(2+); Xref=ChEBI:CHEBI:18420;
CC Evidence={ECO:0000255|HAMAP-Rule:MF_00038,
CC ECO:0000269|PubMed:23990562, ECO:0000269|PubMed:27088606,
CC ECO:0000269|PubMed:29459785};
CC Name=Mn(2+); Xref=ChEBI:CHEBI:29035;
CC Evidence={ECO:0000269|PubMed:23990562};
CC -!- ACTIVITY REGULATION: Inhibited by natural nucleoside antibiotics
CC including tunicamycin, capuramycin and muraymycin. Usually the cofactor
CC magnesium is not required for antibiotic binding.
CC {ECO:0000269|PubMed:23990562, ECO:0000269|PubMed:27088606,
CC ECO:0000269|PubMed:29459785}.
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=190 uM for UDP-MurNAc-pentapeptide {ECO:0000269|PubMed:27088606};
CC -!- PATHWAY: Cell wall biogenesis; peptidoglycan biosynthesis.
CC {ECO:0000255|HAMAP-Rule:MF_00038}.
CC -!- SUBUNIT: Homodimer. {ECO:0000269|PubMed:23990562}.
CC -!- INTERACTION:
CC O66465; O66465: mraY; NbExp=5; IntAct=EBI-16071899, EBI-16071899;
CC -!- SUBCELLULAR LOCATION: Cell inner membrane {ECO:0000255|HAMAP-
CC Rule:MF_00038}; Multi-pass membrane protein {ECO:0000255|HAMAP-
CC Rule:MF_00038}.
CC -!- SIMILARITY: Belongs to the glycosyltransferase 4 family. MraY
CC subfamily. {ECO:0000255|HAMAP-Rule:MF_00038}.
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DR EMBL; AE000657; AAC06418.1; -; Genomic_DNA.
DR PIR; F70304; F70304.
DR RefSeq; NP_213025.1; NC_000918.1.
DR RefSeq; WP_010879963.1; NC_000918.1.
DR PDB; 4J72; X-ray; 3.30 A; A/B=1-359.
DR PDB; 5CKR; X-ray; 2.95 A; A=1-359.
DR PDB; 6OYH; X-ray; 2.95 A; A/B/C/D=1-359.
DR PDB; 6OYZ; X-ray; 3.62 A; A/B/C/D=1-359.
DR PDB; 6OZ6; X-ray; 3.70 A; A/B/C/D=1-359.
DR PDBsum; 4J72; -.
DR PDBsum; 5CKR; -.
DR PDBsum; 6OYH; -.
DR PDBsum; 6OYZ; -.
DR PDBsum; 6OZ6; -.
DR AlphaFoldDB; O66465; -.
DR SMR; O66465; -.
DR DIP; DIP-61734N; -.
DR STRING; 224324.aq_053; -.
DR BindingDB; O66465; -.
DR ChEMBL; CHEMBL4295560; -.
DR ABCD; O66465; 1 sequenced antibody.
DR EnsemblBacteria; AAC06418; AAC06418; aq_053.
DR KEGG; aae:aq_053; -.
DR PATRIC; fig|224324.8.peg.41; -.
DR eggNOG; COG0472; Bacteria.
DR HOGENOM; CLU_023982_0_0_0; -.
DR InParanoid; O66465; -.
DR OMA; LMSPLHH; -.
DR OrthoDB; 1151822at2; -.
DR BRENDA; 2.7.8.13; 396.
DR UniPathway; UPA00219; -.
DR Proteomes; UP000000798; Chromosome.
DR GO; GO:0005887; C:integral component of plasma membrane; IBA:GO_Central.
DR GO; GO:0042802; F:identical protein binding; IPI:IntAct.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0008963; F:phospho-N-acetylmuramoyl-pentapeptide-transferase activity; IDA:UniProtKB.
DR GO; GO:0016780; F:phosphotransferase activity, for other substituted phosphate groups; IBA:GO_Central.
DR GO; GO:0051992; F:UDP-N-acetylmuramoyl-L-alanyl-D-glutamyl-meso-2,6-diaminopimelyl-D-alanyl-D-alanine:undecaprenyl-phosphate transferase activity; IEA:UniProtKB-EC.
DR GO; GO:0007049; P:cell cycle; IEA:UniProtKB-KW.
DR GO; GO:0051301; P:cell division; IEA:UniProtKB-KW.
DR GO; GO:0044038; P:cell wall macromolecule biosynthetic process; IBA:GO_Central.
DR GO; GO:0071555; P:cell wall organization; IBA:GO_Central.
DR GO; GO:0009252; P:peptidoglycan biosynthetic process; IEA:UniProtKB-UniRule.
DR GO; GO:0008360; P:regulation of cell shape; IEA:UniProtKB-KW.
DR CDD; cd06852; GT_MraY; 1.
DR HAMAP; MF_00038; MraY; 1.
DR InterPro; IPR000715; Glycosyl_transferase_4.
DR InterPro; IPR003524; PNAcMuramoyl-5peptid_Trfase.
DR InterPro; IPR018480; PNAcMuramoyl-5peptid_Trfase_CS.
DR PANTHER; PTHR22926; PTHR22926; 1.
DR Pfam; PF00953; Glycos_transf_4; 1.
DR Pfam; PF10555; MraY_sig1; 1.
DR TIGRFAMs; TIGR00445; mraY; 1.
DR PROSITE; PS01347; MRAY_1; 1.
DR PROSITE; PS01348; MRAY_2; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Cell cycle; Cell division; Cell inner membrane;
KW Cell membrane; Cell shape; Cell wall biogenesis/degradation; Magnesium;
KW Manganese; Membrane; Metal-binding; Peptidoglycan synthesis;
KW Reference proteome; Transferase; Transmembrane; Transmembrane helix.
FT CHAIN 1..359
FT /note="Phospho-N-acetylmuramoyl-pentapeptide-transferase"
FT /id="PRO_0000108772"
FT TOPO_DOM 1..25
FT /note="Periplasmic"
FT /evidence="ECO:0000269|PubMed:23990562"
FT TRANSMEM 26..48
FT /note="Helical; Name=Helix 1"
FT /evidence="ECO:0000269|PubMed:23990562"
FT TOPO_DOM 49..74
FT /note="Cytoplasmic"
FT /evidence="ECO:0000269|PubMed:23990562"
FT TRANSMEM 75..92
FT /note="Helical; Name=Helix 2"
FT /evidence="ECO:0000269|PubMed:23990562"
FT TOPO_DOM 93..98
FT /note="Periplasmic"
FT /evidence="ECO:0000269|PubMed:23990562"
FT TRANSMEM 99..120
FT /note="Helical; Name=Helix 3"
FT /evidence="ECO:0000269|PubMed:23990562"
FT TOPO_DOM 121..130
FT /note="Cytoplasmic"
FT /evidence="ECO:0000269|PubMed:23990562"
FT TRANSMEM 131..152
FT /note="Helical; Name=Helix 4"
FT /evidence="ECO:0000269|PubMed:23990562"
FT TOPO_DOM 153..172
FT /note="Periplasmic"
FT /evidence="ECO:0000269|PubMed:23990562"
FT TRANSMEM 173..194
FT /note="Helical; Name=Helix 5"
FT /evidence="ECO:0000269|PubMed:23990562"
FT TOPO_DOM 195..197
FT /note="Cytoplasmic"
FT /evidence="ECO:0000269|PubMed:23990562"
FT TRANSMEM 198..218
FT /note="Helical; Name=Helix 6"
FT /evidence="ECO:0000269|PubMed:23990562"
FT TOPO_DOM 219..233
FT /note="Periplasmic"
FT /evidence="ECO:0000269|PubMed:23990562"
FT TRANSMEM 234..255
FT /note="Helical; Name=Helix 7"
FT /evidence="ECO:0000269|PubMed:23990562"
FT TOPO_DOM 256..264
FT /note="Cytoplasmic"
FT /evidence="ECO:0000269|PubMed:23990562"
FT TRANSMEM 265..280
FT /note="Helical; Name=Helix 8"
FT /evidence="ECO:0000269|PubMed:23990562"
FT TOPO_DOM 281..284
FT /note="Periplasmic"
FT /evidence="ECO:0000269|PubMed:23990562"
FT TRANSMEM 285..310
FT /note="Helical; Name=Helix 9"
FT /evidence="ECO:0000269|PubMed:23990562"
FT TOPO_DOM 311..332
FT /note="Cytoplasmic"
FT /evidence="ECO:0000269|PubMed:23990562"
FT TRANSMEM 333..355
FT /note="Helical; Name=Helix 10"
FT /evidence="ECO:0000269|PubMed:23990562"
FT TOPO_DOM 356..359
FT /note="Periplasmic"
FT /evidence="ECO:0000269|PubMed:23990562"
FT BINDING 70
FT /ligand="muraymycin D2"
FT /ligand_id="ChEBI:CHEBI:178053"
FT /ligand_note="inhibitor"
FT /evidence="ECO:0000269|PubMed:27088606,
FT ECO:0007744|PDB:5CKR"
FT BINDING 75
FT /ligand="muraymycin D2"
FT /ligand_id="ChEBI:CHEBI:178053"
FT /ligand_note="inhibitor"
FT /evidence="ECO:0000269|PubMed:27088606,
FT ECO:0007744|PDB:5CKR"
FT BINDING 190
FT /ligand="muraymycin D2"
FT /ligand_id="ChEBI:CHEBI:178053"
FT /ligand_note="inhibitor"
FT /evidence="ECO:0000269|PubMed:27088606,
FT ECO:0007744|PDB:5CKR"
FT BINDING 193
FT /ligand="muraymycin D2"
FT /ligand_id="ChEBI:CHEBI:178053"
FT /ligand_note="inhibitor"
FT /evidence="ECO:0000269|PubMed:27088606,
FT ECO:0007744|PDB:5CKR"
FT BINDING 196
FT /ligand="muraymycin D2"
FT /ligand_id="ChEBI:CHEBI:178053"
FT /ligand_note="inhibitor"
FT /evidence="ECO:0000269|PubMed:27088606,
FT ECO:0007744|PDB:5CKR"
FT BINDING 264
FT /ligand="muraymycin D2"
FT /ligand_id="ChEBI:CHEBI:178053"
FT /ligand_note="inhibitor"
FT /evidence="ECO:0000269|PubMed:27088606,
FT ECO:0007744|PDB:5CKR"
FT BINDING 268
FT /ligand="muraymycin D2"
FT /ligand_id="ChEBI:CHEBI:178053"
FT /ligand_note="inhibitor"
FT /evidence="ECO:0000269|PubMed:27088606,
FT ECO:0007744|PDB:5CKR"
FT BINDING 305
FT /ligand="muraymycin D2"
FT /ligand_id="ChEBI:CHEBI:178053"
FT /ligand_note="inhibitor"
FT /evidence="ECO:0000269|PubMed:27088606,
FT ECO:0007744|PDB:5CKR"
FT BINDING 321
FT /ligand="muraymycin D2"
FT /ligand_id="ChEBI:CHEBI:178053"
FT /ligand_note="inhibitor"
FT /evidence="ECO:0000269|PubMed:27088606,
FT ECO:0007744|PDB:5CKR"
FT MUTAGEN 70
FT /note="K->A: Reduces binding to inhibitor."
FT /evidence="ECO:0000269|PubMed:27088606"
FT MUTAGEN 117
FT /note="D->A: Loss of catalytic activity."
FT /evidence="ECO:0000269|PubMed:23990562"
FT MUTAGEN 118
FT /note="D->A: Loss of catalytic activity."
FT /evidence="ECO:0000269|PubMed:23990562"
FT MUTAGEN 190
FT /note="N->A: Loss of catalytic activity."
FT /evidence="ECO:0000269|PubMed:27088606"
FT MUTAGEN 193
FT /note="D->A: Loss of catalytic activity."
FT /evidence="ECO:0000269|PubMed:27088606"
FT MUTAGEN 196
FT /note="D->A: Loss of catalytic activity."
FT /evidence="ECO:0000269|PubMed:27088606"
FT MUTAGEN 196
FT /note="D->N: Loss of catalytic activity."
FT /evidence="ECO:0000269|PubMed:27088606"
FT MUTAGEN 262
FT /note="F->A: Impairs binding to inhibitor."
FT /evidence="ECO:0000269|PubMed:27088606"
FT MUTAGEN 262
FT /note="F->W: Reduces binding to inhibitor."
FT /evidence="ECO:0000269|PubMed:27088606"
FT MUTAGEN 265
FT /note="D->A: Loss of catalytic activity. Reduces binding to
FT inhibitor."
FT /evidence="ECO:0000269|PubMed:23990562,
FT ECO:0000269|PubMed:29459785"
FT MUTAGEN 305
FT /note="Q->A: Impairs binding to inhibitor."
FT /evidence="ECO:0000269|PubMed:27088606"
FT MUTAGEN 324
FT /note="H->A: Loss of catalytic activity."
FT /evidence="ECO:0000269|PubMed:23990562"
FT MUTAGEN 325
FT /note="H->A: Reduces the catalytic activity."
FT /evidence="ECO:0000269|PubMed:23990562"
FT MUTAGEN 326
FT /note="H->A: Reduces the catalytic activity."
FT /evidence="ECO:0000269|PubMed:23990562"
FT HELIX 21..56
FT /evidence="ECO:0007829|PDB:5CKR"
FT STRAND 71..73
FT /evidence="ECO:0007829|PDB:5CKR"
FT HELIX 78..92
FT /evidence="ECO:0007829|PDB:5CKR"
FT TURN 95..97
FT /evidence="ECO:0007829|PDB:5CKR"
FT HELIX 99..124
FT /evidence="ECO:0007829|PDB:5CKR"
FT HELIX 130..149
FT /evidence="ECO:0007829|PDB:5CKR"
FT STRAND 157..159
FT /evidence="ECO:0007829|PDB:5CKR"
FT STRAND 167..169
FT /evidence="ECO:0007829|PDB:5CKR"
FT HELIX 171..173
FT /evidence="ECO:0007829|PDB:5CKR"
FT HELIX 174..192
FT /evidence="ECO:0007829|PDB:5CKR"
FT TURN 196..199
FT /evidence="ECO:0007829|PDB:6OYH"
FT HELIX 200..216
FT /evidence="ECO:0007829|PDB:5CKR"
FT HELIX 220..225
FT /evidence="ECO:0007829|PDB:5CKR"
FT TURN 232..234
FT /evidence="ECO:0007829|PDB:6OYH"
FT HELIX 235..255
FT /evidence="ECO:0007829|PDB:5CKR"
FT STRAND 256..258
FT /evidence="ECO:0007829|PDB:5CKR"
FT HELIX 264..281
FT /evidence="ECO:0007829|PDB:5CKR"
FT HELIX 285..291
FT /evidence="ECO:0007829|PDB:5CKR"
FT HELIX 293..312
FT /evidence="ECO:0007829|PDB:5CKR"
FT STRAND 317..322
FT /evidence="ECO:0007829|PDB:5CKR"
FT HELIX 323..329
FT /evidence="ECO:0007829|PDB:5CKR"
FT HELIX 334..356
FT /evidence="ECO:0007829|PDB:5CKR"
SQ SEQUENCE 359 AA; 40341 MW; B2D6292EA6EA16D4 CRC64;
MLYQLALLLK DYWFAFNVLK YITFRSFTAV LIAFFLTLVL SPSFINRLRK IQRLFGGYVR
EYTPESHEVK KYTPTMGGIV ILIVVTLSTL LLMRWDIKYT WVVLLSFLSF GTIGFWDDYV
KLKNKKGISI KTKFLLQVLS ASLISVLIYY WADIDTILYF PFFKELYVDL GVLYLPFAVF
VIVGSANAVN LTDGLDGLAI GPAMTTATAL GVVAYAVGHS KIAQYLNIPY VPYAGELTVF
CFALVGAGLG FLWFNSFPAQ MFMGDVGSLS IGASLATVAL LTKSEFIFAV AAGVFVFETI
SVILQIIYFR WTGGKRLFKR APFHHHLELN GLPEPKIVVR MWIISILLAI IAISMLKLR
