DXMT1_COFCA
ID DXMT1_COFCA Reviewed; 384 AA.
AC A4GE70; A0A068VAE8; A0A096VHZ9;
DT 31-MAY-2011, integrated into UniProtKB/Swiss-Prot.
DT 11-DEC-2019, sequence version 2.
DT 03-AUG-2022, entry version 53.
DE RecName: Full=3,7-dimethylxanthine N-methyltransferase {ECO:0000303|PubMed:17401201};
DE Short=CcDXMT {ECO:0000303|PubMed:25249475};
DE EC=2.1.1.160 {ECO:0000269|PubMed:17434991};
DE AltName: Full=Caffeine synthase DXMT {ECO:0000305};
GN Name=DXMT {ECO:0000303|PubMed:17401201};
GN ORFNames=GSCOC_T00011062001 {ECO:0000312|EMBL:CDP17572.1};
OS Coffea canephora (Robusta coffee).
OC Eukaryota; Viridiplantae; Streptophyta; Embryophyta; Tracheophyta;
OC Spermatophyta; Magnoliopsida; eudicotyledons; Gunneridae; Pentapetalae;
OC asterids; lamiids; Gentianales; Rubiaceae; Ixoroideae; Gardenieae complex;
OC Bertiereae - Coffeeae clade; Coffeeae; Coffea.
OX NCBI_TaxID=49390;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, CRYSTALLIZATION, AND PATHWAY.
RX PubMed=17401201; DOI=10.1107/s1744309107009268;
RA McCarthy A.A., Biget L., Lin C., Petiard V., Tanksley S.D., McCarthy J.G.;
RT "Cloning, expression, crystallization and preliminary X-ray analysis of the
RT XMT and DXMT N-methyltransferases from Coffea canephora (robusta).";
RL Acta Crystallogr. F 63:304-307(2007).
RN [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA], TISSUE SPECIFICITY, DEVELOPMENTAL
RP STAGE, GENE FAMILY, AND NOMENCLATURE.
RC STRAIN=cv. DH200-94;
RX PubMed=25249475; DOI=10.1007/s00425-014-2170-7;
RA Perrois C., Strickler S.R., Mathieu G., Lepelley M., Bedon L., Michaux S.,
RA Husson J., Mueller L., Privat I.;
RT "Differential regulation of caffeine metabolism in Coffea arabica (Arabica)
RT and Coffea canephora (Robusta).";
RL Planta 241:179-191(2015).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA], TISSUE SPECIFICITY, AND
RP DEVELOPMENTAL STAGE.
RC STRAIN=cv. DH200-94;
RX PubMed=25190796; DOI=10.1126/science.1255274;
RA Denoeud F., Carretero-Paulet L., Dereeper A., Droc G., Guyot R.,
RA Pietrella M., Zheng C., Alberti A., Anthony F., Aprea G., Aury J.M.,
RA Bento P., Bernard M., Bocs S., Campa C., Cenci A., Combes M.C.,
RA Crouzillat D., Da Silva C., Daddiego L., De Bellis F., Dussert S.,
RA Garsmeur O., Gayraud T., Guignon V., Jahn K., Jamilloux V., Joet T.,
RA Labadie K., Lan T., Leclercq J., Lepelley M., Leroy T., Li L.T.,
RA Librado P., Lopez L., Munoz A., Noel B., Pallavicini A., Perrotta G.,
RA Poncet V., Pot D., Priyono X., Rigoreau M., Rouard M., Rozas J.,
RA Tranchant-Dubreuil C., VanBuren R., Zhang Q., Andrade A.C., Argout X.,
RA Bertrand B., de Kochko A., Graziosi G., Henry R.J., Jayarama X., Ming R.,
RA Nagai C., Rounsley S., Sankoff D., Giuliano G., Albert V.A., Wincker P.,
RA Lashermes P.;
RT "The coffee genome provides insight into the convergent evolution of
RT caffeine biosynthesis.";
RL Science 345:1181-1184(2014).
RN [4]
RP REVIEW ON CAFFEINE BIOSYNTHESIS.
RX PubMed=18068204; DOI=10.1016/j.phytochem.2007.10.029;
RA Ashihara H., Sano H., Crozier A.;
RT "Caffeine and related purine alkaloids: biosynthesis, catabolism, function
RT and genetic engineering.";
RL Phytochemistry 69:841-856(2008).
RN [5]
RP X-RAY CRYSTALLOGRAPHY (2.0 ANGSTROMS) IN COMPLEX WITH
RP S-ADENOSYL-L-HOMOCYSTEINE AND THEOBROMINE, FUNCTION, SUBUNIT, CATALYTIC
RP ACTIVITY, AND PATHWAY.
RX PubMed=17434991; DOI=10.1104/pp.106.094854;
RA McCarthy A.A., McCarthy J.G.;
RT "The structure of two N-methyltransferases from the caffeine biosynthetic
RT pathway.";
RL Plant Physiol. 144:879-889(2007).
CC -!- FUNCTION: Involved in the biosynthesis of caffeine (PubMed:17401201,
CC PubMed:17434991). Catalyzes the conversion of 7-methylxanthine to
CC caffeine, likely via theobromine as an intermediate (PubMed:17434991).
CC {ECO:0000269|PubMed:17401201, ECO:0000269|PubMed:17434991}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=S-adenosyl-L-methionine + theobromine = caffeine + H(+) + S-
CC adenosyl-L-homocysteine; Xref=Rhea:RHEA:20944, ChEBI:CHEBI:15378,
CC ChEBI:CHEBI:27732, ChEBI:CHEBI:28946, ChEBI:CHEBI:57856,
CC ChEBI:CHEBI:59789; EC=2.1.1.160;
CC Evidence={ECO:0000269|PubMed:17434991};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:20945;
CC Evidence={ECO:0000269|PubMed:17434991};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=1,7-dimethylxanthine + S-adenosyl-L-methionine = caffeine +
CC H(+) + S-adenosyl-L-homocysteine; Xref=Rhea:RHEA:10280,
CC ChEBI:CHEBI:15378, ChEBI:CHEBI:25858, ChEBI:CHEBI:27732,
CC ChEBI:CHEBI:57856, ChEBI:CHEBI:59789; EC=2.1.1.160;
CC Evidence={ECO:0000269|PubMed:17434991};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:10281;
CC Evidence={ECO:0000269|PubMed:17434991};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=7-methylxanthine + S-adenosyl-L-methionine = H(+) + S-
CC adenosyl-L-homocysteine + theobromine; Xref=Rhea:RHEA:24604,
CC ChEBI:CHEBI:15378, ChEBI:CHEBI:28946, ChEBI:CHEBI:48991,
CC ChEBI:CHEBI:57856, ChEBI:CHEBI:59789; EC=2.1.1.160;
CC Evidence={ECO:0000269|PubMed:17434991};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:24605;
CC Evidence={ECO:0000269|PubMed:17434991};
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 -!- PATHWAY: Alkaloid biosynthesis. {ECO:0000269|PubMed:17401201,
CC ECO:0000269|PubMed:17434991}.
CC -!- SUBUNIT: Homodimer. {ECO:0000269|PubMed:17434991}.
CC -!- TISSUE SPECIFICITY: Mainly expressed in leaves and fruits (grains)
CC (PubMed:25249475, PubMed:25190796). Also present, at lower levels, in
CC roots, stamens and pistils (PubMed:25190796).
CC {ECO:0000269|PubMed:25190796, ECO:0000269|PubMed:25249475}.
CC -!- DEVELOPMENTAL STAGE: In leaves, mostly expressed in young tissues
CC (PubMed:25249475). In fruits, highly expressed in green grains but
CC fades out as they are yellowing to disappear in red mature grains
CC (PubMed:25249475, PubMed:25190796). {ECO:0000269|PubMed:25190796,
CC ECO:0000269|PubMed:25249475}.
CC -!- SIMILARITY: Belongs to the methyltransferase superfamily. Type-7
CC methyltransferase family. {ECO:0000305}.
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DR EMBL; DQ422955; ABD90686.1; -; mRNA.
DR EMBL; JX978506; AFV60434.1; -; Genomic_DNA.
DR EMBL; JX978516; AFV60444.1; -; mRNA.
DR EMBL; HG739252; CDP17572.1; -; Genomic_DNA.
DR PDB; 2EFJ; X-ray; 2.00 A; A=1-384.
DR PDBsum; 2EFJ; -.
DR AlphaFoldDB; A4GE70; -.
DR SMR; A4GE70; -.
DR EnsemblPlants; CDP17572; CDP17572; GSCOC_T00011062001.
DR Gramene; CDP17572; CDP17572; GSCOC_T00011062001.
DR OMA; AICIRAV; -.
DR BRENDA; 2.1.1.159; 7042.
DR BRENDA; 2.1.1.160; 7042.
DR EvolutionaryTrace; A4GE70; -.
DR Proteomes; UP000295252; Chromosome 1.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0102741; F:paraxanthine:S-adenosyl-L-methionine 3-N-methyltransferase activity; IEA:UniProtKB-EC.
DR GO; GO:0102740; F:theobromine:S-adenosyl-L-methionine 1-N-methyltransferase activity; IEA:UniProtKB-EC.
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; Reference proteome; S-adenosyl-L-methionine;
KW Transferase.
FT CHAIN 1..384
FT /note="3,7-dimethylxanthine N-methyltransferase"
FT /id="PRO_0000408470"
FT BINDING 18
FT /ligand="S-adenosyl-L-methionine"
FT /ligand_id="ChEBI:CHEBI:59789"
FT /evidence="ECO:0000269|PubMed:17434991,
FT ECO:0007744|PDB:2EFJ"
FT BINDING 18
FT /ligand="substrate"
FT /evidence="ECO:0000269|PubMed:17434991,
FT ECO:0007744|PDB:2EFJ"
FT BINDING 21..25
FT /ligand="substrate"
FT /evidence="ECO:0000250|UniProtKB:A4GE69"
FT BINDING 60..61
FT /ligand="S-adenosyl-L-methionine"
FT /ligand_id="ChEBI:CHEBI:59789"
FT /evidence="ECO:0000250|UniProtKB:Q9FLN8"
FT BINDING 60
FT /ligand="S-adenosyl-L-methionine"
FT /ligand_id="ChEBI:CHEBI:59789"
FT /evidence="ECO:0000269|PubMed:17434991,
FT ECO:0007744|PDB:2EFJ"
FT BINDING 61
FT /ligand="S-adenosyl-L-methionine"
FT /ligand_id="ChEBI:CHEBI:59789"
FT /evidence="ECO:0000250|UniProtKB:A0A6C0WW36"
FT BINDING 66
FT /ligand="S-adenosyl-L-methionine"
FT /ligand_id="ChEBI:CHEBI:59789"
FT /evidence="ECO:0000269|PubMed:17434991,
FT ECO:0007744|PDB:2EFJ"
FT BINDING 98..101
FT /ligand="S-adenosyl-L-methionine"
FT /ligand_id="ChEBI:CHEBI:59789"
FT /evidence="ECO:0000269|PubMed:17434991,
FT ECO:0007744|PDB:2EFJ"
FT BINDING 139..141
FT /ligand="S-adenosyl-L-methionine"
FT /ligand_id="ChEBI:CHEBI:59789"
FT /evidence="ECO:0000269|PubMed:17434991,
FT ECO:0007744|PDB:2EFJ"
FT BINDING 156..158
FT /ligand="S-adenosyl-L-methionine"
FT /ligand_id="ChEBI:CHEBI:59789"
FT /evidence="ECO:0000269|PubMed:17434991,
FT ECO:0007744|PDB:2EFJ"
FT BINDING 157..161
FT /ligand="substrate"
FT /evidence="ECO:0000269|PubMed:17434991,
FT ECO:0007744|PDB:2EFJ"
FT BINDING 178
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /evidence="ECO:0000250|UniProtKB:Q9FLN8"
FT BINDING 237
FT /ligand="substrate"
FT /evidence="ECO:0000269|PubMed:17434991,
FT ECO:0007744|PDB:2EFJ"
FT BINDING 260
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /evidence="ECO:0000250|UniProtKB:Q9FLN8"
FT BINDING 262
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /evidence="ECO:0000250|UniProtKB:Q9FLN8"
FT BINDING 263
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /evidence="ECO:0000250|UniProtKB:Q9FLN8"
FT BINDING 333
FT /ligand="substrate"
FT /evidence="ECO:0000250|UniProtKB:A4GE69"
FT BINDING 368
FT /ligand="substrate"
FT /evidence="ECO:0000269|PubMed:17434991,
FT ECO:0007744|PDB:2EFJ"
FT SITE 154
FT /note="Involved in substrate discrimination"
FT /evidence="ECO:0000250|UniProtKB:Q9FZN8"
FT SITE 266
FT /note="Involved in substrate discrimination"
FT /evidence="ECO:0000250|UniProtKB:Q9FZN8"
FT SITE 328
FT /note="Involved in substrate discrimination"
FT /evidence="ECO:0000250|UniProtKB:Q9FZN8"
FT SITE 343
FT /note="Involved in substrate discrimination"
FT /evidence="ECO:0000250|UniProtKB:Q9FZN8"
FT CONFLICT 250
FT /note="V -> I (in Ref. 1; ABD90686)"
FT CONFLICT 293
FT /note="Y -> N (in Ref. 1; ABD90686)"
FT CONFLICT 382..384
FT /note="ADM -> SDV (in Ref. 2; AFV60434/AFV60444)"
FT /evidence="ECO:0000305"
FT TURN 4..6
FT /evidence="ECO:0007829|PDB:2EFJ"
FT HELIX 18..21
FT /evidence="ECO:0007829|PDB:2EFJ"
FT TURN 24..27
FT /evidence="ECO:0007829|PDB:2EFJ"
FT HELIX 28..44
FT /evidence="ECO:0007829|PDB:2EFJ"
FT TURN 48..52
FT /evidence="ECO:0007829|PDB:2EFJ"
FT STRAND 53..60
FT /evidence="ECO:0007829|PDB:2EFJ"
FT HELIX 65..78
FT /evidence="ECO:0007829|PDB:2EFJ"
FT STRAND 93..99
FT /evidence="ECO:0007829|PDB:2EFJ"
FT HELIX 106..123
FT /evidence="ECO:0007829|PDB:2EFJ"
FT STRAND 130..135
FT /evidence="ECO:0007829|PDB:2EFJ"
FT STRAND 150..157
FT /evidence="ECO:0007829|PDB:2EFJ"
FT STRAND 163..165
FT /evidence="ECO:0007829|PDB:2EFJ"
FT STRAND 182..184
FT /evidence="ECO:0007829|PDB:2EFJ"
FT HELIX 190..214
FT /evidence="ECO:0007829|PDB:2EFJ"
FT STRAND 215..226
FT /evidence="ECO:0007829|PDB:2EFJ"
FT TURN 230..232
FT /evidence="ECO:0007829|PDB:2EFJ"
FT HELIX 237..250
FT /evidence="ECO:0007829|PDB:2EFJ"
FT HELIX 256..260
FT /evidence="ECO:0007829|PDB:2EFJ"
FT HELIX 271..281
FT /evidence="ECO:0007829|PDB:2EFJ"
FT STRAND 283..295
FT /evidence="ECO:0007829|PDB:2EFJ"
FT TURN 296..299
FT /evidence="ECO:0007829|PDB:2EFJ"
FT HELIX 315..341
FT /evidence="ECO:0007829|PDB:2EFJ"
FT HELIX 346..363
FT /evidence="ECO:0007829|PDB:2EFJ"
FT STRAND 367..377
FT /evidence="ECO:0007829|PDB:2EFJ"
SQ SEQUENCE 384 AA; 43389 MW; CBB6732C362B889F CRC64;
MELQEVLHMN GGEGDTSYAK NSSYNLFLIR VKPVLEQCIQ ELLRANLPNI NKCFKVGDLG
CASGPNTFST VRDIVQSIDK VGQEKKNELE RPTIQIFLND LFQNDFNSVF KLLPSFYRNL
EKENGRKIGS CLIGAMPGSF YSRLFPEESM HFLHSCYCLH WLSQVPSGLV TELGISVNKG
CIYSSKASRP PIQKAYLDQF TKDFTTFLRI HSEELISRGR MLLTFICKED EFDHPNSMDL
LEMSINDLVV EGHLEEEKLD SFNVPIYAPS TEEVKRIVEE EGSFEILYLE TFYAPYDAGF
SIDDDYQGRS HSPVSCDEHA RAAHVASVVR SIYEPILASH FGEAILPDLS HRIAKNAAKV
LRSGKGFYDS VIISLAKKPE KADM
