EGTD_MYCTO
ID EGTD_MYCTO Reviewed; 321 AA.
AC P9WN46; L0TG93; O69669; Q7D514;
DT 16-APR-2014, integrated into UniProtKB/Swiss-Prot.
DT 16-APR-2014, sequence version 1.
DT 03-AUG-2022, entry version 41.
DE RecName: Full=Histidine N-alpha-methyltransferase;
DE EC=2.1.1.44 {ECO:0000250|UniProtKB:A0R5M8};
DE AltName: Full=Histidine trimethyltransferase;
GN Name=egtD; OrderedLocusNames=MT3804;
OS Mycobacterium tuberculosis (strain CDC 1551 / Oshkosh).
OC Bacteria; Actinobacteria; Corynebacteriales; Mycobacteriaceae;
OC Mycobacterium; Mycobacterium tuberculosis complex.
OX NCBI_TaxID=83331;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=CDC 1551 / Oshkosh;
RX PubMed=12218036; DOI=10.1128/jb.184.19.5479-5490.2002;
RA Fleischmann R.D., Alland D., Eisen J.A., Carpenter L., White O.,
RA Peterson J.D., DeBoy R.T., Dodson R.J., Gwinn M.L., Haft D.H., Hickey E.K.,
RA Kolonay J.F., Nelson W.C., Umayam L.A., Ermolaeva M.D., Salzberg S.L.,
RA Delcher A., Utterback T.R., Weidman J.F., Khouri H.M., Gill J., Mikula A.,
RA Bishai W., Jacobs W.R. Jr., Venter J.C., Fraser C.M.;
RT "Whole-genome comparison of Mycobacterium tuberculosis clinical and
RT laboratory strains.";
RL J. Bacteriol. 184:5479-5490(2002).
RN [2]
RP FUNCTION, PATHWAY, INDUCTION, OPERON STRUCTURE, AND DISRUPTION PHENOTYPE.
RC STRAIN=CDC 1551 / Oshkosh;
RX PubMed=26774486; DOI=10.1016/j.celrep.2015.12.056;
RA Saini V., Cumming B.M., Guidry L., Lamprecht D.A., Adamson J.H.,
RA Reddy V.P., Chinta K.C., Mazorodze J.H., Glasgow J.N.,
RA Richard-Greenblatt M., Gomez-Velasco A., Bach H., Av-Gay Y., Eoh H.,
RA Rhee K., Steyn A.J.;
RT "Ergothioneine maintains redox and bioenergetic homeostasis essential for
RT drug susceptibility and virulence of Mycobacterium tuberculosis.";
RL Cell Rep. 14:572-585(2016).
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 (ERG). ERG is one of the major redox buffers
CC which protects bacteria against redox stressors and antibiotics; loss
CC of ERG or mycothiol (MSH, the other major redox buffer in this
CC bacteria) leads to respiratory alterations and bioenergetic
CC deficiencies that negatively impact virulence (PubMed:26774486).
CC {ECO:0000250|UniProtKB:A0R5M8, ECO:0000305|PubMed:26774486}.
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:0000250|UniProtKB:A0R5M8};
CC -!- PATHWAY: Amino-acid biosynthesis; ergothioneine biosynthesis.
CC {ECO:0000250|UniProtKB:A0R5M8, ECO:0000305|PubMed:26774486}.
CC -!- SUBUNIT: Monomer. {ECO:0000250|UniProtKB:A0R5M8}.
CC -!- INDUCTION: Expressed in log phase, part of the egtA-egtB-egtC-egtD
CC operon, which does not include egtE (PubMed:26774486).
CC {ECO:0000269|PubMed:26774486}.
CC -!- DISRUPTION PHENOTYPE: Loss of production of ergothioneine (ERG), no
CC alteration in ratio of oxidized versus reduced mycothiol (MSH),
CC decreased resistance to compounds that cause oxidative stress,
CC decreased resistance to the antibitoics rifampicin, isoniazid,
CC bedaquiline and clofazimine (PubMed:26774486). Absence leads to
CC alteration of transcript levels for 74 genes which probably compensate
CC for loss of redox control (PubMed:26774486). Decreased bacterial
CC survival in mouse macrophage cell line, 4-fold decreased bacterial
CC burden in infected mice lungs (strain BALB/c), no alteration in mouse
CC lung ERG levels (PubMed:26774486). {ECO:0000269|PubMed:26774486}.
CC -!- SIMILARITY: Belongs to the methyltransferase superfamily. EgtD family.
CC {ECO:0000305}.
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DR EMBL; AE000516; AAK48171.1; -; Genomic_DNA.
DR PIR; F70793; F70793.
DR RefSeq; WP_003419799.1; NZ_KK341227.1.
DR AlphaFoldDB; P9WN46; -.
DR SMR; P9WN46; -.
DR PRIDE; P9WN46; -.
DR EnsemblBacteria; AAK48171; AAK48171; MT3804.
DR KEGG; mtc:MT3804; -.
DR PATRIC; fig|83331.31.peg.4096; -.
DR HOGENOM; CLU_049766_1_0_11; -.
DR UniPathway; UPA01014; -.
DR Proteomes; UP000001020; Chromosome.
DR GO; GO:0030745; F:dimethylhistidine N-methyltransferase activity; IEA:UniProtKB-UniRule.
DR GO; GO:0008276; F:protein methyltransferase activity; ISS:UniProtKB.
DR GO; GO:0052704; P:ergothioneine biosynthesis from histidine via gamma-glutamyl-hercynylcysteine sulfoxide; ISS:UniProtKB.
DR GO; GO:0052707; P:N-alpha,N-alpha,N-alpha-trimethyl-L-histidine biosynthesis from histidine; ISS: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 2: Evidence at transcript level;
KW Methyltransferase; S-adenosyl-L-methionine; Transferase.
FT CHAIN 1..321
FT /note="Histidine N-alpha-methyltransferase"
FT /id="PRO_0000427190"
FT BINDING 56
FT /ligand="L-histidine"
FT /ligand_id="ChEBI:CHEBI:57595"
FT /evidence="ECO:0000250|UniProtKB:A0R5M8"
FT BINDING 86
FT /ligand="S-adenosyl-L-methionine"
FT /ligand_id="ChEBI:CHEBI:59789"
FT /evidence="ECO:0000250|UniProtKB:A0R5M8"
FT BINDING 92
FT /ligand="S-adenosyl-L-methionine"
FT /ligand_id="ChEBI:CHEBI:59789"
FT /evidence="ECO:0000250|UniProtKB:A0R5M8"
FT BINDING 113
FT /ligand="S-adenosyl-L-methionine"
FT /ligand_id="ChEBI:CHEBI:59789"
FT /evidence="ECO:0000250|UniProtKB:A0R5M8"
FT BINDING 141..142
FT /ligand="S-adenosyl-L-methionine"
FT /ligand_id="ChEBI:CHEBI:59789"
FT /evidence="ECO:0000250|UniProtKB:A0R5M8"
FT BINDING 166
FT /ligand="L-histidine"
FT /ligand_id="ChEBI:CHEBI:57595"
FT /evidence="ECO:0000250|UniProtKB:A0R5M8"
FT BINDING 206
FT /ligand="L-histidine"
FT /ligand_id="ChEBI:CHEBI:57595"
FT /evidence="ECO:0000250|UniProtKB:A0R5M8"
FT BINDING 282..284
FT /ligand="L-histidine"
FT /ligand_id="ChEBI:CHEBI:57595"
FT /evidence="ECO:0000250|UniProtKB:A0R5M8"
SQ SEQUENCE 321 AA; 35404 MW; 28FE9989B22A9D77 CRC64;
MRVSVANHLG EDAGHLALRR DVYSGLQKTP KSLPPKWFYD TVGSELFDQI TRLPEYYPTR
AEAEILRARS AEVASACRAD TLVELGSGTS EKTRMLLDAL RHRGSLRRFV PFDVDASVLS
ATATAIQREY SGVEINAVCG DFEEHLTEIP RGGRRLFVFL GSTIGNLTPG PRAQFLTALA
GVMRPGDSLL LGTDLVKDAA RLVRAYDDPG GVTAQFNRNV LAVINRELEA DFDVDAFQHV
ARWNSAEERI EMWLRADGRQ RVRVGALDLT VDFDAGEEML TEVSCKFRPQ AVGAELAAAG
LHRIRWWTDE AGDFGLSLAA K
