CKTCS_CAMSB
ID CKTCS_CAMSB Reviewed; 370 AA.
AC A0A6C0WW36;
DT 10-FEB-2021, integrated into UniProtKB/Swiss-Prot.
DT 17-JUN-2020, sequence version 1.
DT 03-AUG-2022, entry version 9.
DE RecName: Full=1,3,7-trimethyluric acid N-methyltransferase CkTcS {ECO:0000303|PubMed:32193380};
DE EC=2.1.1.- {ECO:0000269|PubMed:32193380};
DE AltName: Full=Theacrine synthase {ECO:0000303|PubMed:32193380};
DE Short=CkTcS {ECO:0000303|PubMed:32193380};
GN Name=TCS {ECO:0000303|PubMed:32193380};
OS Camellia sinensis var. assamica (Assam tea) (Thea assamica).
OC Eukaryota; Viridiplantae; Streptophyta; Embryophyta; Tracheophyta;
OC Spermatophyta; Magnoliopsida; eudicotyledons; Gunneridae; Pentapetalae;
OC asterids; Ericales; Theaceae; Camellia.
OX NCBI_TaxID=261999;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], X-RAY CRYSTALLOGRAPHY (3.15 ANGSTROMS) IN
RP COMPLEX WITH S-ADENOSYL-L-HOMOCYSTEINE, FUNCTION, CATALYTIC ACTIVITY,
RP PATHWAY, TISSUE SPECIFICITY, AND BIOPHYSICOCHEMICAL PROPERTIES.
RC STRAIN=cv. Kucha, and cv. Puer;
RX PubMed=32193380; DOI=10.1038/s41467-020-15324-7;
RA Zhang Y.-H., Li Y.-F., Wang Y., Tan L., Cao Z.-Q., Xie C., Xie G.,
RA Gong H.-B., Sun W.-Y., Ouyang S.-H., Duan W.-J., Lu X., Ding K.,
RA Kurihara H., Hu D., Zhang Z.-M., Abe I., He R.-R.;
RT "Identification and characterization of N9-methyltransferase involved in
RT converting caffeine into non-stimulatory theacrine in tea.";
RL Nat. Commun. 11:1473-1473(2020).
CC -!- FUNCTION: Involved in the biosynthesis of theacrine, a caffeine-like
CC xanthine alkaloid with diverse beneficial biological activities
CC including anti-depressive, sedative, and hypnotic activities, improving
CC learning and memory, increasing exercise activity, and preventing
CC nonalcoholic fatty liver disease (PubMed:32193380). Mediates the
CC conversion of 1,3,7-trimethyluric acid to theacrine (PubMed:32193380).
CC {ECO:0000269|PubMed:32193380}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=1,3,7-trimethylurate + S-adenosyl-L-methionine = H(+) + S-
CC adenosyl-L-homocysteine + theacrine; Xref=Rhea:RHEA:65536,
CC ChEBI:CHEBI:15378, ChEBI:CHEBI:57856, ChEBI:CHEBI:59789,
CC ChEBI:CHEBI:139388, ChEBI:CHEBI:691622;
CC Evidence={ECO:0000269|PubMed:32193380};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:65537;
CC Evidence={ECO:0000269|PubMed:32193380};
CC -!- COFACTOR:
CC Name=Mg(2+); Xref=ChEBI:CHEBI:18420;
CC Evidence={ECO:0000250|UniProtKB:Q9FLN8};
CC Note=Binds 1 Mg(2+) ion per subunit. {ECO:0000250|UniProtKB:Q9FLN8};
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=4.68 uM for 1,3,7-trimethyluric acid
CC {ECO:0000269|PubMed:32193380};
CC Note=kcat is 0.01142 sec(-1) with 1,3,7-trimethyluric acid as
CC substrate. {ECO:0000269|PubMed:32193380};
CC -!- PATHWAY: Alkaloid biosynthesis. {ECO:0000269|PubMed:32193380}.
CC -!- TISSUE SPECIFICITY: Expressed in leaves of cv. Kucha, but not in cv.
CC Puer. {ECO:0000269|PubMed:32193380}.
CC -!- MISCELLANEOUS: Caffeine is catabolized to produce theacrine in Camellia
CC sinensis var. assamica cv. Kucha, but not in cv. Puer.
CC {ECO:0000305|PubMed:32193380}.
CC -!- SIMILARITY: Belongs to the methyltransferase superfamily. Type-7
CC methyltransferase family. {ECO:0000305}.
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DR EMBL; MN163831; QIC50344.1; -; mRNA.
DR PDB; 6LYH; X-ray; 3.15 A; A/B/C/D/E/F/G/H=8-370.
DR PDBsum; 6LYH; -.
DR AlphaFoldDB; A0A6C0WW36; -.
DR SMR; A0A6C0WW36; -.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0008168; F:methyltransferase activity; IEA:UniProtKB-KW.
DR GO; GO:0009820; P:alkaloid metabolic process; IEA:UniProtKB-KW.
DR GO; GO:0032259; P:methylation; IEA:UniProtKB-KW.
DR Gene3D; 1.10.1200.270; -; 1.
DR Gene3D; 3.40.50.150; -; 1.
DR InterPro; IPR005299; MeTrfase_7.
DR InterPro; IPR042086; MeTrfase_capping.
DR InterPro; IPR029063; SAM-dependent_MTases_sf.
DR PANTHER; PTHR31009; PTHR31009; 1.
DR Pfam; PF03492; Methyltransf_7; 1.
DR SUPFAM; SSF53335; SSF53335; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Alkaloid metabolism; Magnesium; Metal-binding;
KW Methyltransferase; S-adenosyl-L-methionine; Transferase.
FT CHAIN 1..370
FT /note="1,3,7-trimethyluric acid N-methyltransferase CkTcS"
FT /id="PRO_0000451802"
FT BINDING 24
FT /ligand="S-adenosyl-L-methionine"
FT /ligand_id="ChEBI:CHEBI:59789"
FT /evidence="ECO:0000269|PubMed:32193380,
FT ECO:0007744|PDB:6LYH"
FT BINDING 24
FT /ligand="substrate"
FT /evidence="ECO:0000250|UniProtKB:A4GE70"
FT BINDING 27..31
FT /ligand="substrate"
FT /evidence="ECO:0000269|PubMed:32193380,
FT ECO:0007744|PDB:6LYH"
FT BINDING 66..67
FT /ligand="S-adenosyl-L-methionine"
FT /ligand_id="ChEBI:CHEBI:59789"
FT /evidence="ECO:0000250|UniProtKB:Q9FLN8"
FT BINDING 66
FT /ligand="S-adenosyl-L-methionine"
FT /ligand_id="ChEBI:CHEBI:59789"
FT /evidence="ECO:0000250|UniProtKB:A4GE69"
FT BINDING 67
FT /ligand="S-adenosyl-L-methionine"
FT /ligand_id="ChEBI:CHEBI:59789"
FT /evidence="ECO:0000269|PubMed:32193380,
FT ECO:0007744|PDB:6LYH"
FT BINDING 72
FT /ligand="S-adenosyl-L-methionine"
FT /ligand_id="ChEBI:CHEBI:59789"
FT /evidence="ECO:0000269|PubMed:32193380,
FT ECO:0007744|PDB:6LYH"
FT BINDING 102..105
FT /ligand="S-adenosyl-L-methionine"
FT /ligand_id="ChEBI:CHEBI:59789"
FT /evidence="ECO:0000269|PubMed:32193380,
FT ECO:0007744|PDB:6LYH"
FT BINDING 139..141
FT /ligand="S-adenosyl-L-methionine"
FT /ligand_id="ChEBI:CHEBI:59789"
FT /evidence="ECO:0000269|PubMed:32193380,
FT ECO:0007744|PDB:6LYH"
FT BINDING 156..158
FT /ligand="S-adenosyl-L-methionine"
FT /ligand_id="ChEBI:CHEBI:59789"
FT /evidence="ECO:0000250|UniProtKB:A4GE69"
FT BINDING 157..161
FT /ligand="substrate"
FT /evidence="ECO:0000269|PubMed:32193380,
FT ECO:0007744|PDB:6LYH"
FT BINDING 178
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /evidence="ECO:0000250|UniProtKB:Q9FLN8"
FT BINDING 264
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /evidence="ECO:0000250|UniProtKB:Q9FLN8"
FT BINDING 266
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /evidence="ECO:0000250|UniProtKB:Q9FLN8"
FT BINDING 267
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /evidence="ECO:0000250|UniProtKB:Q9FLN8"
FT SITE 154
FT /note="Involved in substrate discrimination"
FT /evidence="ECO:0000250|UniProtKB:Q9FZN8"
FT SITE 226
FT /note="Involved in substrate discrimination"
FT /evidence="ECO:0000250|UniProtKB:Q9FZN8"
FT SITE 270
FT /note="Involved in substrate discrimination"
FT /evidence="ECO:0000250|UniProtKB:Q9FZN8"
FT SITE 318
FT /note="Involved in substrate discrimination"
FT /evidence="ECO:0000250|UniProtKB:Q9FZN8"
FT SITE 333
FT /note="Involved in substrate discrimination"
FT /evidence="ECO:0000250|UniProtKB:Q9FZN8"
FT STRAND 18..23
FT /evidence="ECO:0007829|PDB:6LYH"
FT TURN 24..26
FT /evidence="ECO:0007829|PDB:6LYH"
FT HELIX 29..46
FT /evidence="ECO:0007829|PDB:6LYH"
FT HELIX 48..51
FT /evidence="ECO:0007829|PDB:6LYH"
FT STRAND 55..66
FT /evidence="ECO:0007829|PDB:6LYH"
FT HELIX 73..91
FT /evidence="ECO:0007829|PDB:6LYH"
FT STRAND 97..103
FT /evidence="ECO:0007829|PDB:6LYH"
FT TURN 107..110
FT /evidence="ECO:0007829|PDB:6LYH"
FT HELIX 111..117
FT /evidence="ECO:0007829|PDB:6LYH"
FT HELIX 119..122
FT /evidence="ECO:0007829|PDB:6LYH"
FT STRAND 131..135
FT /evidence="ECO:0007829|PDB:6LYH"
FT STRAND 150..157
FT /evidence="ECO:0007829|PDB:6LYH"
FT STRAND 163..165
FT /evidence="ECO:0007829|PDB:6LYH"
FT TURN 177..180
FT /evidence="ECO:0007829|PDB:6LYH"
FT HELIX 190..214
FT /evidence="ECO:0007829|PDB:6LYH"
FT STRAND 215..226
FT /evidence="ECO:0007829|PDB:6LYH"
FT STRAND 229..232
FT /evidence="ECO:0007829|PDB:6LYH"
FT HELIX 236..254
FT /evidence="ECO:0007829|PDB:6LYH"
FT HELIX 260..263
FT /evidence="ECO:0007829|PDB:6LYH"
FT HELIX 275..284
FT /evidence="ECO:0007829|PDB:6LYH"
FT STRAND 285..298
FT /evidence="ECO:0007829|PDB:6LYH"
FT HELIX 308..331
FT /evidence="ECO:0007829|PDB:6LYH"
FT TURN 332..335
FT /evidence="ECO:0007829|PDB:6LYH"
FT HELIX 336..348
FT /evidence="ECO:0007829|PDB:6LYH"
FT TURN 349..353
FT /evidence="ECO:0007829|PDB:6LYH"
FT STRAND 358..367
FT /evidence="ECO:0007829|PDB:6LYH"
SQ SEQUENCE 370 AA; 41606 MW; 49C72A7198F3C45B CRC64;
MELATRGKVK EVLFMNTGEG ESSYVQNSSF TEKVASMAMP ALENAVETLF SKDFHLFQAI
NAADLGCATG PNTFAVISTI KRMMEKKCRE LNCQTLELQV YMNDLFGNDF NTLFKGLSSK
VIGNKCEEVS CYVMGVPGSF HGRLFPRNSL HLVHSSYSVH WLTQAPKGLT SREGLALNKG
RIYISKTSPP VVREAYLSQF HEDFTMFLNA RSQEVVPNGC MVLILRGRQS SDPSDMQSCF
IWELLAIAIA ELVSQGLIDE DKLDTFNIPC YFPSLEEVKD IVERDGSFTI DHMEGFELDS
LQMQENDKWV RGEKFAKIVR AFTEPIISNQ FGHEIMDKLY DKFTHIVVSD LEAKLPKTTS
IILVLSKIVG
