EGTD_MYCS2
ID EGTD_MYCS2 Reviewed; 321 AA.
AC A0R5M8; I7GAE1;
DT 19-OCT-2011, integrated into UniProtKB/Swiss-Prot.
DT 09-JAN-2007, sequence version 1.
DT 03-AUG-2022, entry version 99.
DE RecName: Full=Histidine N-alpha-methyltransferase {ECO:0000305};
DE EC=2.1.1.44 {ECO:0000269|PubMed:20420449, ECO:0000269|PubMed:25404173};
DE AltName: Full=Histidine trimethyltransferase {ECO:0000303|PubMed:25251321};
GN Name=egtD {ECO:0000303|PubMed:20420449};
GN OrderedLocusNames=MSMEG_6247, MSMEI_6086;
OS Mycolicibacterium smegmatis (strain ATCC 700084 / mc(2)155) (Mycobacterium
OS smegmatis).
OC Bacteria; Actinobacteria; Corynebacteriales; Mycobacteriaceae;
OC Mycolicibacterium.
OX NCBI_TaxID=246196;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=ATCC 700084 / mc(2)155;
RA Fleischmann R.D., Dodson R.J., Haft D.H., Merkel J.S., Nelson W.C.,
RA Fraser C.M.;
RL Submitted (OCT-2006) to the EMBL/GenBank/DDBJ databases.
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=ATCC 700084 / mc(2)155;
RX PubMed=17295914; DOI=10.1186/gb-2007-8-2-r20;
RA Deshayes C., Perrodou E., Gallien S., Euphrasie D., Schaeffer C.,
RA Van-Dorsselaer A., Poch O., Lecompte O., Reyrat J.-M.;
RT "Interrupted coding sequences in Mycobacterium smegmatis: authentic
RT mutations or sequencing errors?";
RL Genome Biol. 8:R20.1-R20.9(2007).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=ATCC 700084 / mc(2)155;
RX PubMed=18955433; DOI=10.1101/gr.081901.108;
RA Gallien S., Perrodou E., Carapito C., Deshayes C., Reyrat J.-M.,
RA Van Dorsselaer A., Poch O., Schaeffer C., Lecompte O.;
RT "Ortho-proteogenomics: multiple proteomes investigation through orthology
RT and a new MS-based protocol.";
RL Genome Res. 19:128-135(2009).
RN [4]
RP FUNCTION, CATALYTIC ACTIVITY, SUBSTRATE SPECIFICITY, GENE NAME, AND
RP PATHWAY.
RC STRAIN=ATCC 607 / DSM 43465 / JCM 20379 / NBRC 3207 / NRRL B-692;
RX PubMed=20420449; DOI=10.1021/ja101721e;
RA Seebeck F.P.;
RT "In vitro reconstitution of Mycobacterial ergothioneine biosynthesis.";
RL J. Am. Chem. Soc. 132:6632-6633(2010).
RN [5]
RP DISRUPTION PHENOTYPE, AND PATHWAY.
RC STRAIN=ATCC 700084 / mc(2)155;
RX PubMed=23629716; DOI=10.1128/aac.02572-12;
RA Sao Emani C., Williams M.J., Wiid I.J., Hiten N.F., Viljoen A.J.,
RA Pietersen R.D., van Helden P.D., Baker B.;
RT "Ergothioneine is a secreted antioxidant in Mycobacterium smegmatis.";
RL Antimicrob. Agents Chemother. 57:3202-3207(2013).
RN [6]
RP CRYSTALLIZATION, AND SUBUNIT.
RC STRAIN=ATCC 607 / DSM 43465 / JCM 20379 / NBRC 3207 / NRRL B-692;
RX PubMed=24817736; DOI=10.1107/s2053230x1400805x;
RA Vit A., Misson L., Blankenfeldt W., Seebeck F.P.;
RT "Crystallization and preliminary X-ray analysis of the ergothioneine-
RT biosynthetic methyltransferase EgtD.";
RL Acta Crystallogr. F 70:676-680(2014).
RN [7]
RP X-RAY CRYSTALLOGRAPHY (2.00 ANGSTROMS) OF APOENYZME AND COMPLEXES WITH
RP L-HISTIDINE AND S-ADENOSYL-L-HOMOCYSTEINE, DOMAIN, SUBUNIT, AND REACTION
RP MECHANISM.
RX PubMed=25251321; DOI=10.1016/j.bbrc.2014.09.058;
RA Jeong J.H., Cha H.J., Ha S.C., Rojviriya C., Kim Y.G.;
RT "Structural insights into the histidine trimethylation activity of EgtD
RT from Mycobacterium smegmatis.";
RL Biochem. Biophys. Res. Commun. 452:1098-1103(2014).
RN [8]
RP X-RAY CRYSTALLOGRAPHY (1.51 ANGSTROMS) OF APOENYZME; WILD-TYPE IN COMPLEXES
RP WITH N,N-DIMETHYL-L-HISTIDINE AND S-ADENOSYL-L-HOMOCYSTEINE (SAH) AND
RP MUTANT VAL-252/ALA-282 IN COMPLEX WITH TRYPTOPHAN AND SAH, FUNCTION,
RP CATALYTIC ACTIVITY, BIOPHYSICOCHEMICAL PROPERTIES, AND MUTAGENESIS OF
RP MET-252 AND GLU-282.
RC STRAIN=ATCC 607 / DSM 43465 / JCM 20379 / NBRC 3207 / NRRL B-692;
RX PubMed=25404173; DOI=10.1002/cbic.201402522;
RA Vit A., Misson L., Blankenfeldt W., Seebeck F.P.;
RT "Ergothioneine biosynthetic methyltransferase EgtD reveals the structural
RT basis of aromatic amino acid betaine biosynthesis.";
RL ChemBioChem 16:119-125(2015).
CC -!- FUNCTION: Catalyzes the SAM-dependent triple methylation of the alpha-
CC amino group of histidine to form hercynine, a step in the biosynthesis
CC pathway of ergothioneine. Among all the proteinogenic amino acids, only
CC L-histidine is a substrate. {ECO:0000269|PubMed:20420449,
CC ECO:0000269|PubMed:25404173}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=L-histidine + 3 S-adenosyl-L-methionine = 3 H(+) + hercynine +
CC 3 S-adenosyl-L-homocysteine; Xref=Rhea:RHEA:38471, ChEBI:CHEBI:15378,
CC ChEBI:CHEBI:15781, ChEBI:CHEBI:57595, ChEBI:CHEBI:57856,
CC ChEBI:CHEBI:59789; EC=2.1.1.44;
CC Evidence={ECO:0000269|PubMed:20420449, ECO:0000269|PubMed:25404173};
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=109 uM for L-histidine {ECO:0000269|PubMed:25404173};
CC KM=17.7 uM for N-alpha-methyl-L-histidine
CC {ECO:0000269|PubMed:25404173};
CC KM=25.3 uM for N-alpha,N-alpha-dimethyl-L-histidine
CC {ECO:0000269|PubMed:25404173};
CC Note=kcat is 0.58 sec(-1) for the methylation of L-histidine. kcat is
CC 0.23 sec(-1) for the methylation of N-alpha-methyl-L-histidine. kcat
CC is 0.23 sec(-1) for the methylation of N-alpha,N-alpha-dimethyl-L-
CC histidine. {ECO:0000269|PubMed:25404173};
CC -!- PATHWAY: Amino-acid biosynthesis; ergothioneine biosynthesis.
CC {ECO:0000269|PubMed:23629716, ECO:0000305|PubMed:20420449}.
CC -!- SUBUNIT: Monomer. {ECO:0000269|PubMed:24817736,
CC ECO:0000269|PubMed:25251321}.
CC -!- DOMAIN: Consists of two distinct domains: a typical methyltransferase
CC domain and a unique substrate binding domain.
CC {ECO:0000305|PubMed:25251321}.
CC -!- DISRUPTION PHENOTYPE: Cells lacking this gene are unable to synthesize
CC ergothioneine (ERG), but do not show growth defect. Deletion of egtD
CC from wild-type M.smegmatis and a mycothiol (MSH)-deficient mutant does
CC not affect their susceptibility to tested antibiotics. The ERG- and
CC MSH-deficient double mutant is significantly more sensitive to peroxide
CC than either of the single mutants lacking either ERG or MSH, suggesting
CC that both thiols play a role in protecting M.smegmatis against
CC oxidative stress and that ERG is able to partly compensate for the loss
CC of MSH. {ECO:0000269|PubMed:23629716}.
CC -!- SIMILARITY: Belongs to the methyltransferase superfamily. EgtD family.
CC {ECO:0000305}.
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DR EMBL; CP000480; ABK75457.1; -; Genomic_DNA.
DR EMBL; CP001663; AFP42517.1; -; Genomic_DNA.
DR RefSeq; WP_011731156.1; NZ_SIJM01000027.1.
DR RefSeq; YP_890466.1; NC_008596.1.
DR PDB; 4PIM; X-ray; 1.75 A; A/B=1-321.
DR PDB; 4PIN; X-ray; 1.90 A; A/B=1-321.
DR PDB; 4PIO; X-ray; 1.51 A; A/B=1-321.
DR PDB; 4PIP; X-ray; 1.80 A; A/B/C/D=1-321.
DR PDB; 4UY5; X-ray; 2.00 A; A=1-321.
DR PDB; 4UY6; X-ray; 2.04 A; A=2-321.
DR PDB; 4UY7; X-ray; 2.31 A; A/B=2-321.
DR PDB; 6FNQ; X-ray; 1.75 A; A/B=3-321.
DR PDB; 6FNR; X-ray; 1.83 A; A/B=3-321.
DR PDB; 6FNS; X-ray; 1.85 A; A/B=3-321.
DR PDB; 6FNT; X-ray; 1.90 A; A/B=3-321.
DR PDBsum; 4PIM; -.
DR PDBsum; 4PIN; -.
DR PDBsum; 4PIO; -.
DR PDBsum; 4PIP; -.
DR PDBsum; 4UY5; -.
DR PDBsum; 4UY6; -.
DR PDBsum; 4UY7; -.
DR PDBsum; 6FNQ; -.
DR PDBsum; 6FNR; -.
DR PDBsum; 6FNS; -.
DR PDBsum; 6FNT; -.
DR AlphaFoldDB; A0R5M8; -.
DR SMR; A0R5M8; -.
DR STRING; 246196.MSMEI_6086; -.
DR PRIDE; A0R5M8; -.
DR EnsemblBacteria; ABK75457; ABK75457; MSMEG_6247.
DR EnsemblBacteria; AFP42517; AFP42517; MSMEI_6086.
DR GeneID; 66737530; -.
DR KEGG; msg:MSMEI_6086; -.
DR KEGG; msm:MSMEG_6247; -.
DR PATRIC; fig|246196.19.peg.6086; -.
DR eggNOG; COG4301; Bacteria.
DR OMA; RVEMHLV; -.
DR OrthoDB; 775492at2; -.
DR BioCyc; MetaCyc:MON-17984; -.
DR BRENDA; 2.1.1.44; 3512.
DR UniPathway; UPA01014; -.
DR Proteomes; UP000000757; Chromosome.
DR Proteomes; UP000006158; Chromosome.
DR GO; GO:0030745; F:dimethylhistidine N-methyltransferase activity; IEA:UniProtKB-UniRule.
DR GO; GO:0008276; F:protein methyltransferase activity; IDA:UniProtKB.
DR GO; GO:0052704; P:ergothioneine biosynthesis from histidine via gamma-glutamyl-hercynylcysteine sulfoxide; IDA:UniProtKB.
DR GO; GO:0052707; P:N-alpha,N-alpha,N-alpha-trimethyl-L-histidine biosynthesis from histidine; IDA:UniProtKB.
DR Gene3D; 3.40.50.150; -; 2.
DR HAMAP; MF_02037; EgtD; 1.
DR InterPro; IPR035094; EgtD.
DR InterPro; IPR032888; EgtD_Actinobacteria.
DR InterPro; IPR019257; MeTrfase_dom.
DR InterPro; IPR017804; MeTrfase_EgtD-like.
DR InterPro; IPR029063; SAM-dependent_MTases_sf.
DR Pfam; PF10017; Methyltransf_33; 1.
DR PIRSF; PIRSF018005; UCP018005; 1.
DR SUPFAM; SSF53335; SSF53335; 1.
DR TIGRFAMs; TIGR03438; egtD_ergothio; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Methyltransferase; Reference proteome;
KW S-adenosyl-L-methionine; Transferase.
FT CHAIN 1..321
FT /note="Histidine N-alpha-methyltransferase"
FT /id="PRO_0000413651"
FT BINDING 56
FT /ligand="L-histidine"
FT /ligand_id="ChEBI:CHEBI:57595"
FT /evidence="ECO:0000269|PubMed:25251321,
FT ECO:0000305|PubMed:25404173, ECO:0007744|PDB:4UY6,
FT ECO:0007744|PDB:4UY7"
FT BINDING 86
FT /ligand="S-adenosyl-L-methionine"
FT /ligand_id="ChEBI:CHEBI:59789"
FT /evidence="ECO:0000305|PubMed:25251321,
FT ECO:0000305|PubMed:25404173"
FT BINDING 92
FT /ligand="S-adenosyl-L-methionine"
FT /ligand_id="ChEBI:CHEBI:59789"
FT /evidence="ECO:0000305|PubMed:25251321,
FT ECO:0000305|PubMed:25404173"
FT BINDING 113
FT /ligand="S-adenosyl-L-methionine"
FT /ligand_id="ChEBI:CHEBI:59789"
FT /evidence="ECO:0000305|PubMed:25251321,
FT ECO:0000305|PubMed:25404173"
FT BINDING 141..142
FT /ligand="S-adenosyl-L-methionine"
FT /ligand_id="ChEBI:CHEBI:59789"
FT /evidence="ECO:0000305|PubMed:25251321,
FT ECO:0000305|PubMed:25404173, ECO:0007744|PDB:4PIO,
FT ECO:0007744|PDB:4PIP, ECO:0007744|PDB:4UY6"
FT BINDING 166
FT /ligand="L-histidine"
FT /ligand_id="ChEBI:CHEBI:57595"
FT /evidence="ECO:0000269|PubMed:25251321,
FT ECO:0000305|PubMed:25404173, ECO:0007744|PDB:4UY6,
FT ECO:0007744|PDB:4UY7"
FT BINDING 206
FT /ligand="L-histidine"
FT /ligand_id="ChEBI:CHEBI:57595"
FT /evidence="ECO:0000269|PubMed:25251321,
FT ECO:0000305|PubMed:25404173, ECO:0007744|PDB:4UY6,
FT ECO:0007744|PDB:4UY7"
FT BINDING 282..284
FT /ligand="L-histidine"
FT /ligand_id="ChEBI:CHEBI:57595"
FT /evidence="ECO:0000269|PubMed:25251321,
FT ECO:0000305|PubMed:25404173, ECO:0007744|PDB:4UY6,
FT ECO:0007744|PDB:4UY7"
FT MUTAGEN 252
FT /note="M->V: Dramatic change in substrate specificity since
FT the tryptophan-specific activity is increased more than
FT 2000-fold and the histidine-specific activity is reduced
FT 3000-fold; when associated with A-282."
FT /evidence="ECO:0000269|PubMed:25404173"
FT MUTAGEN 282
FT /note="E->A: 130-fold reduction in catalytic efficiency.
FT Dramatic change in substrate specificity since the
FT tryptophan-specific activity is increased more than 2000-
FT fold and the histidine-specific activity is reduced 3000-
FT fold; when associated with V-252."
FT /evidence="ECO:0000269|PubMed:25404173"
FT STRAND 5..10
FT /evidence="ECO:0007829|PDB:4PIO"
FT HELIX 11..14
FT /evidence="ECO:0007829|PDB:4PIO"
FT HELIX 16..27
FT /evidence="ECO:0007829|PDB:4PIO"
FT STRAND 28..30
FT /evidence="ECO:0007829|PDB:4PIO"
FT HELIX 35..38
FT /evidence="ECO:0007829|PDB:4PIO"
FT HELIX 41..50
FT /evidence="ECO:0007829|PDB:4PIO"
FT STRAND 53..55
FT /evidence="ECO:0007829|PDB:6FNT"
FT HELIX 58..77
FT /evidence="ECO:0007829|PDB:4PIO"
FT STRAND 80..85
FT /evidence="ECO:0007829|PDB:4PIO"
FT HELIX 93..102
FT /evidence="ECO:0007829|PDB:4PIO"
FT STRAND 108..114
FT /evidence="ECO:0007829|PDB:4PIO"
FT HELIX 116..129
FT /evidence="ECO:0007829|PDB:4PIO"
FT STRAND 138..140
FT /evidence="ECO:0007829|PDB:4PIO"
FT TURN 142..144
FT /evidence="ECO:0007829|PDB:4PIO"
FT HELIX 146..148
FT /evidence="ECO:0007829|PDB:4PIO"
FT STRAND 153..159
FT /evidence="ECO:0007829|PDB:4PIO"
FT HELIX 163..166
FT /evidence="ECO:0007829|PDB:4PIO"
FT HELIX 169..180
FT /evidence="ECO:0007829|PDB:4PIO"
FT STRAND 188..195
FT /evidence="ECO:0007829|PDB:4PIO"
FT HELIX 199..205
FT /evidence="ECO:0007829|PDB:4PIO"
FT HELIX 212..228
FT /evidence="ECO:0007829|PDB:4PIO"
FT HELIX 234..236
FT /evidence="ECO:0007829|PDB:4PIO"
FT STRAND 237..244
FT /evidence="ECO:0007829|PDB:4PIO"
FT TURN 245..248
FT /evidence="ECO:0007829|PDB:4PIO"
FT STRAND 249..258
FT /evidence="ECO:0007829|PDB:4PIO"
FT STRAND 260..264
FT /evidence="ECO:0007829|PDB:4PIO"
FT HELIX 265..267
FT /evidence="ECO:0007829|PDB:4PIO"
FT STRAND 269..273
FT /evidence="ECO:0007829|PDB:4PIO"
FT STRAND 278..285
FT /evidence="ECO:0007829|PDB:4PIO"
FT HELIX 289..298
FT /evidence="ECO:0007829|PDB:4PIO"
FT STRAND 302..308
FT /evidence="ECO:0007829|PDB:4PIO"
FT STRAND 314..320
FT /evidence="ECO:0007829|PDB:4PIO"
SQ SEQUENCE 321 AA; 35003 MW; 43FE091F6B4A48D6 CRC64;
MTLSLANYLA ADSAAEALRR DVRAGLTAAP KSLPPKWFYD AVGSDLFDQI TRLPEYYPTR
TEAQILRTRS AEIIAAAGAD TLVELGSGTS EKTRMLLDAM RDAELLRRFI PFDVDAGVLR
SAGAAIGAEY PGIEIDAVCG DFEEHLGKIP HVGRRLVVFL GSTIGNLTPA PRAEFLSTLA
DTLQPGDSLL LGTDLVKDTG RLVRAYDDAA GVTAAFNRNV LAVVNRELSA DFDLDAFEHV
AKWNSDEERI EMWLRARTAQ HVRVAALDLE VDFAAGEEML TEVSCKFRPE NVVAELAEAG
LRQTHWWTDP AGDFGLSLAV R
