TYLM1_STRFR
ID TYLM1_STRFR Reviewed; 255 AA.
AC P95748;
DT 05-SEP-2012, integrated into UniProtKB/Swiss-Prot.
DT 01-NOV-1999, sequence version 2.
DT 03-AUG-2022, entry version 82.
DE RecName: Full=dTDP-3-amino-3,6-dideoxy-alpha-D-glucopyranose N,N-dimethyltransferase;
DE EC=2.1.1.235;
DE AltName: Full=Tylosin biosynthesis protein M1;
GN Name=tylM1; Synonyms=tylMI;
OS Streptomyces fradiae (Streptomyces roseoflavus).
OC Bacteria; Actinobacteria; Streptomycetales; Streptomycetaceae;
OC Streptomyces.
OX NCBI_TaxID=1906;
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], FUNCTION, AND PATHWAY.
RC STRAIN=T59235;
RX PubMed=9031628; DOI=10.1016/s0378-1119(96)00595-1;
RA Gandecha A.R., Large S.L., Cundliffe E.;
RT "Analysis of four tylosin biosynthetic genes from the tylLM region of
RT Streptomyces fradiae.";
RL Gene 184:197-203(1997).
RN [2]
RP PROTEIN SEQUENCE OF 2-11, FUNCTION, CATALYTIC ACTIVITY, SUBUNIT, AND
RP BIOPHYSICOCHEMICAL PROPERTIES.
RX PubMed=12119032; DOI=10.1021/bi020245j;
RA Chen H., Yamase H., Murakami K., Chang C.W., Zhao L., Zhao Z., Liu H.W.;
RT "Expression, purification, and characterization of two N,N-
RT dimethyltransferases, tylM1 and desVI, involved in the biosynthesis of
RT mycaminose and desosamine.";
RL Biochemistry 41:9165-9183(2002).
RN [3]
RP X-RAY CRYSTALLOGRAPHY (1.35 ANGSTROMS) IN COMPLEX WITH
RP S-ADENOSYL-L-METHIONINE, FUNCTION, SUBUNIT, AND MUTAGENESIS OF HIS-123.
RX PubMed=21142177; DOI=10.1021/bi101733y;
RA Carney A.E., Holden H.M.;
RT "Molecular architecture of TylM1 from Streptomyces fradiae: an N,N-
RT dimethyltransferase involved in the production of dTDP-D-mycaminose.";
RL Biochemistry 50:780-787(2011).
CC -!- FUNCTION: S-adenosyl-L-methionine-dependent methyltransferase involved
CC in the biosynthesis of mycaminose, an essential structural component of
CC the macrolide antibiotic tylosin. Involved in the last step in
CC mycaminose biosynthesis by mediating dimethylation of the hexose C-3'
CC amino group. {ECO:0000269|PubMed:12119032, ECO:0000269|PubMed:21142177,
CC ECO:0000269|PubMed:9031628}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=dTDP-3-amino-3,6-dideoxy-alpha-D-glucose + 2 S-adenosyl-L-
CC methionine = dTDP-alpha-D-mycaminose + 2 H(+) + 2 S-adenosyl-L-
CC homocysteine; Xref=Rhea:RHEA:31671, ChEBI:CHEBI:15378,
CC ChEBI:CHEBI:57856, ChEBI:CHEBI:59789, ChEBI:CHEBI:63265,
CC ChEBI:CHEBI:63268; EC=2.1.1.235;
CC Evidence={ECO:0000269|PubMed:12119032};
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=118.4 uM for dTDP-3-amino-3,4,6-trideoxy-alpha-D-glucopyranose
CC {ECO:0000269|PubMed:12119032};
CC KM=46.8 uM for TDP-3-N-methylamino-3,6-dideoxy-R-D-glucopyranose
CC {ECO:0000269|PubMed:12119032};
CC KM=59.4 uM for dTDP-3-amino-3,6-dideoxy-alpha-D-glucopyranose
CC {ECO:0000269|PubMed:12119032};
CC Note=kcat is 7.2 min(-1) with dTDP-3-amino-3,4,6-trideoxy-alpha-D-
CC glucopyranose as substrate. kcat is 32.5 min(-1) with TDP-3-N-
CC methylamino-3,6-dideoxy-R-D-glucopyranose as substrate. kcat is 9.9
CC min(-1) with dTDP-3-amino-3,6-dideoxy-alpha-D-glucopyranose as
CC substrate.;
CC -!- PATHWAY: Antibiotic biosynthesis; tylosin biosynthesis.
CC {ECO:0000269|PubMed:9031628}.
CC -!- SUBUNIT: Homodimer. {ECO:0000269|PubMed:12119032,
CC ECO:0000269|PubMed:21142177}.
CC -!- DOMAIN: His-123 is a strong candicate for an active site that hydrogen
CC bonds to a water molecule which in turn hydrogen bonds to the C-3'
CC amino group. However, it is not conserved in related S.venezuelae DesVI
CC methyltransferase and its mutagenesis does not completely abolish
CC catalytic activity (PubMed:21142177). {ECO:0000269|PubMed:21142177}.
CC -!- SIMILARITY: Belongs to the methyltransferase TylM1/DesVI family.
CC {ECO:0000305}.
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DR EMBL; X81885; CAA57473.2; -; Genomic_DNA.
DR RefSeq; WP_050364681.1; NZ_MCNU01000256.1.
DR PDB; 3PFG; X-ray; 1.35 A; A=1-255.
DR PDB; 3PFH; X-ray; 1.79 A; A/D=1-255.
DR PDB; 3PX2; X-ray; 1.65 A; A/D=1-255.
DR PDB; 3PX3; X-ray; 1.80 A; A/D=1-255.
DR PDB; 4OQD; X-ray; 1.60 A; A/B/C/D=1-255.
DR PDB; 4OQE; X-ray; 2.20 A; A/B=1-255.
DR PDB; 6M81; X-ray; 1.78 A; A/B/C/D=1-255.
DR PDB; 6M82; X-ray; 1.40 A; A=1-255.
DR PDB; 6M83; X-ray; 1.37 A; A=1-255.
DR PDBsum; 3PFG; -.
DR PDBsum; 3PFH; -.
DR PDBsum; 3PX2; -.
DR PDBsum; 3PX3; -.
DR PDBsum; 4OQD; -.
DR PDBsum; 4OQE; -.
DR PDBsum; 6M81; -.
DR PDBsum; 6M82; -.
DR PDBsum; 6M83; -.
DR AlphaFoldDB; P95748; -.
DR SMR; P95748; -.
DR STRING; 1906.SFRA_32300; -.
DR KEGG; ag:CAA57473; -.
DR eggNOG; COG2226; Bacteria.
DR OMA; ITCMFGS; -.
DR BioCyc; MetaCyc:MON-18381; -.
DR BRENDA; 2.1.1.235; 5932.
DR BRENDA; 2.1.1.236; 5932.
DR UniPathway; UPA01018; -.
DR EvolutionaryTrace; P95748; -.
DR GO; GO:0042803; F:protein homodimerization activity; IDA:UniProtKB.
DR GO; GO:0008757; F:S-adenosylmethionine-dependent methyltransferase activity; IDA:UniProtKB.
DR GO; GO:0017000; P:antibiotic biosynthetic process; IDA:UniProtKB.
DR GO; GO:0032259; P:methylation; IDA:UniProtKB.
DR Gene3D; 3.40.50.150; -; 1.
DR InterPro; IPR041698; Methyltransf_25.
DR InterPro; IPR029063; SAM-dependent_MTases_sf.
DR Pfam; PF13649; Methyltransf_25; 1.
DR SUPFAM; SSF53335; SSF53335; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Antibiotic biosynthesis; Direct protein sequencing;
KW Methyltransferase; S-adenosyl-L-methionine; Transferase.
FT INIT_MET 1
FT /note="Removed"
FT /evidence="ECO:0000305|PubMed:12119032"
FT CHAIN 2..255
FT /note="dTDP-3-amino-3,6-dideoxy-alpha-D-glucopyranose N,N-
FT dimethyltransferase"
FT /id="PRO_0000418453"
FT BINDING 14
FT /ligand="S-adenosyl-L-methionine"
FT /ligand_id="ChEBI:CHEBI:59789"
FT /evidence="ECO:0000269|PubMed:21142177"
FT BINDING 22
FT /ligand="S-adenosyl-L-methionine"
FT /ligand_id="ChEBI:CHEBI:59789"
FT /evidence="ECO:0000269|PubMed:21142177"
FT BINDING 33
FT /ligand="S-adenosyl-L-methionine"
FT /ligand_id="ChEBI:CHEBI:59789"
FT /evidence="ECO:0000269|PubMed:21142177"
FT BINDING 58..59
FT /ligand="S-adenosyl-L-methionine"
FT /ligand_id="ChEBI:CHEBI:59789"
FT BINDING 58
FT /ligand="S-adenosyl-L-methionine"
FT /ligand_id="ChEBI:CHEBI:59789"
FT /evidence="ECO:0000269|PubMed:21142177"
FT BINDING 79
FT /ligand="S-adenosyl-L-methionine"
FT /ligand_id="ChEBI:CHEBI:59789"
FT /evidence="ECO:0000269|PubMed:21142177"
FT BINDING 101..102
FT /ligand="S-adenosyl-L-methionine"
FT /ligand_id="ChEBI:CHEBI:59789"
FT BINDING 117
FT /ligand="S-adenosyl-L-methionine"
FT /ligand_id="ChEBI:CHEBI:59789"
FT /evidence="ECO:0000269|PubMed:21142177"
FT MUTAGEN 123
FT /note="H->A,N: Strongly reduced activity."
FT /evidence="ECO:0000269|PubMed:21142177"
FT HELIX 16..28
FT /evidence="ECO:0007829|PDB:3PFG"
FT HELIX 33..47
FT /evidence="ECO:0007829|PDB:3PFG"
FT STRAND 53..57
FT /evidence="ECO:0007829|PDB:3PFG"
FT HELIX 63..68
FT /evidence="ECO:0007829|PDB:3PFG"
FT TURN 69..71
FT /evidence="ECO:0007829|PDB:3PFG"
FT STRAND 72..80
FT /evidence="ECO:0007829|PDB:3PFG"
FT HELIX 82..91
FT /evidence="ECO:0007829|PDB:3PFG"
FT STRAND 95..99
FT /evidence="ECO:0007829|PDB:3PFG"
FT TURN 102..104
FT /evidence="ECO:0007829|PDB:3PFG"
FT STRAND 111..116
FT /evidence="ECO:0007829|PDB:3PFG"
FT HELIX 120..123
FT /evidence="ECO:0007829|PDB:3PFG"
FT HELIX 126..139
FT /evidence="ECO:0007829|PDB:3PFG"
FT STRAND 141..149
FT /evidence="ECO:0007829|PDB:3PFG"
FT TURN 155..157
FT /evidence="ECO:0007829|PDB:3PFG"
FT STRAND 162..170
FT /evidence="ECO:0007829|PDB:3PFG"
FT STRAND 173..184
FT /evidence="ECO:0007829|PDB:3PFG"
FT STRAND 187..198
FT /evidence="ECO:0007829|PDB:3PFG"
FT TURN 199..201
FT /evidence="ECO:0007829|PDB:3PFG"
FT STRAND 202..213
FT /evidence="ECO:0007829|PDB:3PFG"
FT HELIX 217..226
FT /evidence="ECO:0007829|PDB:3PFG"
FT STRAND 229..236
FT /evidence="ECO:0007829|PDB:3PFG"
FT TURN 237..239
FT /evidence="ECO:0007829|PDB:3PFG"
FT STRAND 243..248
FT /evidence="ECO:0007829|PDB:3PFG"
SQ SEQUENCE 255 AA; 27428 MW; 74C1034DA07FA07A CRC64;
MAHSSATAGP QADYSGEIAE LYDLVHQGKG KDYHREAADL AALVRRHSPK AASLLDVACG
TGMHLRHLAD SFGTVEGLEL SADMLAIARR RNPDAVLHHG DMRDFSLGRR FSAVTCMFSS
IGHLAGQAEL DAALERFAAH VLPDGVVVVE PWWFPENFTP GYVAAGTVEA GGTTVTRVSH
SSREGEATRI EVHYLVAGPD RGITHHEESH RITLFTREQY ERAFTAAGLS VEFMPGGPSG
RGLFTGLPGA KGETR
