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1JU6

Human Thymidylate Synthase Complex with dUMP and LY231514, A Pyrrolo(2,3-d)pyrimidine-based Antifolate

Functional Information from GO Data
ChainGOidnamespacecontents
A0000900molecular_functionmRNA regulatory element binding translation repressor activity
A0003729molecular_functionmRNA binding
A0004799molecular_functionthymidylate synthase activity
A0005542molecular_functionfolic acid binding
A0005634cellular_componentnucleus
A0005737cellular_componentcytoplasm
A0005739cellular_componentmitochondrion
A0005743cellular_componentmitochondrial inner membrane
A0005759cellular_componentmitochondrial matrix
A0005829cellular_componentcytosol
A0006206biological_processpyrimidine nucleobase metabolic process
A0006231biological_processdTMP biosynthetic process
A0006235biological_processdTTP biosynthetic process
A0006417biological_processregulation of translation
A0007623biological_processcircadian rhythm
A0008168molecular_functionmethyltransferase activity
A0009165biological_processnucleotide biosynthetic process
A0009410biological_processresponse to xenobiotic stimulus
A0009636biological_processresponse to toxic substance
A0014070biological_processresponse to organic cyclic compound
A0016741molecular_functiontransferase activity, transferring one-carbon groups
A0017148biological_processnegative regulation of translation
A0019860biological_processuracil metabolic process
A0032259biological_processmethylation
A0032570biological_processresponse to progesterone
A0033189biological_processresponse to vitamin A
A0034097biological_processresponse to cytokine
A0035999biological_processtetrahydrofolate interconversion
A0042803molecular_functionprotein homodimerization activity
A0045471biological_processresponse to ethanol
A0046653biological_processtetrahydrofolate metabolic process
A0046683biological_processresponse to organophosphorus
A0048589biological_processdevelopmental growth
A0051216biological_processcartilage development
A0051384biological_processresponse to glucocorticoid
A0051593biological_processresponse to folic acid
A0060574biological_processintestinal epithelial cell maturation
A0071897biological_processDNA biosynthetic process
A0097421biological_processliver regeneration
A1901363molecular_functionheterocyclic compound binding
A1990825molecular_functionsequence-specific mRNA binding
B0000900molecular_functionmRNA regulatory element binding translation repressor activity
B0003729molecular_functionmRNA binding
B0004799molecular_functionthymidylate synthase activity
B0005542molecular_functionfolic acid binding
B0005634cellular_componentnucleus
B0005737cellular_componentcytoplasm
B0005739cellular_componentmitochondrion
B0005743cellular_componentmitochondrial inner membrane
B0005759cellular_componentmitochondrial matrix
B0005829cellular_componentcytosol
B0006206biological_processpyrimidine nucleobase metabolic process
B0006231biological_processdTMP biosynthetic process
B0006235biological_processdTTP biosynthetic process
B0006417biological_processregulation of translation
B0007623biological_processcircadian rhythm
B0008168molecular_functionmethyltransferase activity
B0009165biological_processnucleotide biosynthetic process
B0009410biological_processresponse to xenobiotic stimulus
B0009636biological_processresponse to toxic substance
B0014070biological_processresponse to organic cyclic compound
B0016741molecular_functiontransferase activity, transferring one-carbon groups
B0017148biological_processnegative regulation of translation
B0019860biological_processuracil metabolic process
B0032259biological_processmethylation
B0032570biological_processresponse to progesterone
B0033189biological_processresponse to vitamin A
B0034097biological_processresponse to cytokine
B0035999biological_processtetrahydrofolate interconversion
B0042803molecular_functionprotein homodimerization activity
B0045471biological_processresponse to ethanol
B0046653biological_processtetrahydrofolate metabolic process
B0046683biological_processresponse to organophosphorus
B0048589biological_processdevelopmental growth
B0051216biological_processcartilage development
B0051384biological_processresponse to glucocorticoid
B0051593biological_processresponse to folic acid
B0060574biological_processintestinal epithelial cell maturation
B0071897biological_processDNA biosynthetic process
B0097421biological_processliver regeneration
B1901363molecular_functionheterocyclic compound binding
B1990825molecular_functionsequence-specific mRNA binding
C0000900molecular_functionmRNA regulatory element binding translation repressor activity
C0003729molecular_functionmRNA binding
C0004799molecular_functionthymidylate synthase activity
C0005542molecular_functionfolic acid binding
C0005634cellular_componentnucleus
C0005737cellular_componentcytoplasm
C0005739cellular_componentmitochondrion
C0005743cellular_componentmitochondrial inner membrane
C0005759cellular_componentmitochondrial matrix
C0005829cellular_componentcytosol
C0006206biological_processpyrimidine nucleobase metabolic process
C0006231biological_processdTMP biosynthetic process
C0006235biological_processdTTP biosynthetic process
C0006417biological_processregulation of translation
C0007623biological_processcircadian rhythm
C0008168molecular_functionmethyltransferase activity
C0009165biological_processnucleotide biosynthetic process
C0009410biological_processresponse to xenobiotic stimulus
C0009636biological_processresponse to toxic substance
C0014070biological_processresponse to organic cyclic compound
C0016741molecular_functiontransferase activity, transferring one-carbon groups
C0017148biological_processnegative regulation of translation
C0019860biological_processuracil metabolic process
C0032259biological_processmethylation
C0032570biological_processresponse to progesterone
C0033189biological_processresponse to vitamin A
C0034097biological_processresponse to cytokine
C0035999biological_processtetrahydrofolate interconversion
C0042803molecular_functionprotein homodimerization activity
C0045471biological_processresponse to ethanol
C0046653biological_processtetrahydrofolate metabolic process
C0046683biological_processresponse to organophosphorus
C0048589biological_processdevelopmental growth
C0051216biological_processcartilage development
C0051384biological_processresponse to glucocorticoid
C0051593biological_processresponse to folic acid
C0060574biological_processintestinal epithelial cell maturation
C0071897biological_processDNA biosynthetic process
C0097421biological_processliver regeneration
C1901363molecular_functionheterocyclic compound binding
C1990825molecular_functionsequence-specific mRNA binding
D0000900molecular_functionmRNA regulatory element binding translation repressor activity
D0003729molecular_functionmRNA binding
D0004799molecular_functionthymidylate synthase activity
D0005542molecular_functionfolic acid binding
D0005634cellular_componentnucleus
D0005737cellular_componentcytoplasm
D0005739cellular_componentmitochondrion
D0005743cellular_componentmitochondrial inner membrane
D0005759cellular_componentmitochondrial matrix
D0005829cellular_componentcytosol
D0006206biological_processpyrimidine nucleobase metabolic process
D0006231biological_processdTMP biosynthetic process
D0006235biological_processdTTP biosynthetic process
D0006417biological_processregulation of translation
D0007623biological_processcircadian rhythm
D0008168molecular_functionmethyltransferase activity
D0009165biological_processnucleotide biosynthetic process
D0009410biological_processresponse to xenobiotic stimulus
D0009636biological_processresponse to toxic substance
D0014070biological_processresponse to organic cyclic compound
D0016741molecular_functiontransferase activity, transferring one-carbon groups
D0017148biological_processnegative regulation of translation
D0019860biological_processuracil metabolic process
D0032259biological_processmethylation
D0032570biological_processresponse to progesterone
D0033189biological_processresponse to vitamin A
D0034097biological_processresponse to cytokine
D0035999biological_processtetrahydrofolate interconversion
D0042803molecular_functionprotein homodimerization activity
D0045471biological_processresponse to ethanol
D0046653biological_processtetrahydrofolate metabolic process
D0046683biological_processresponse to organophosphorus
D0048589biological_processdevelopmental growth
D0051216biological_processcartilage development
D0051384biological_processresponse to glucocorticoid
D0051593biological_processresponse to folic acid
D0060574biological_processintestinal epithelial cell maturation
D0071897biological_processDNA biosynthetic process
D0097421biological_processliver regeneration
D1901363molecular_functionheterocyclic compound binding
D1990825molecular_functionsequence-specific mRNA binding
Functional Information from PDB Data
site_idAC1
Number of Residues7
DetailsBINDING SITE FOR RESIDUE PO4 A 316
ChainResidue
AGLN156
AGLY157
BARG185
CGLY155
CGLN156
CGLY157
DARG185

site_idAC2
Number of Residues15
DetailsBINDING SITE FOR RESIDUE UMP A 314
ChainResidue
ACYS195
AHIS196
AGLN214
AARG215
ASER216
AASP218
AASN226
AHIS256
ATYR258
ALYA317
AHOH404
BARG175
BARG176
AARG50
ALEU192

site_idAC3
Number of Residues10
DetailsBINDING SITE FOR RESIDUE LYA A 317
ChainResidue
APHE80
ATRP109
AASN112
AASP218
AGLY222
APHE225
AMET311
AALA312
AUMP314
AHOH411

site_idAC4
Number of Residues17
DetailsBINDING SITE FOR RESIDUE UMP B 314
ChainResidue
AARG175
AARG176
BARG50
BTYR135
BLEU192
BCYS195
BHIS196
BGLN214
BARG215
BSER216
BASP218
BGLY222
BASN226
BHIS256
BTYR258
BLYA315
BHOH416

site_idAC5
Number of Residues10
DetailsBINDING SITE FOR RESIDUE LYA B 315
ChainResidue
BPHE80
BILE108
BTRP109
BASN112
BASP218
BLEU221
BGLY222
BMET311
BALA312
BUMP314

site_idAC6
Number of Residues15
DetailsBINDING SITE FOR RESIDUE UMP C 314
ChainResidue
CARG50
CCYS195
CHIS196
CGLN214
CARG215
CSER216
CASP218
CGLY222
CASN226
CHIS256
CTYR258
CLYA315
CHOH428
DARG175
DARG176

site_idAC7
Number of Residues9
DetailsBINDING SITE FOR RESIDUE LYA C 315
ChainResidue
CPHE80
CILE108
CASN112
CASP218
CGLY222
CMET311
CALA312
CUMP314
CHOH435

site_idAC8
Number of Residues15
DetailsBINDING SITE FOR RESIDUE UMP D 314
ChainResidue
CARG175
CARG176
DARG50
DTYR135
DLEU192
DCYS195
DHIS196
DGLN214
DARG215
DSER216
DASP218
DASN226
DHIS256
DTYR258
DLYA315

site_idAC9
Number of Residues11
DetailsBINDING SITE FOR RESIDUE LYA D 315
ChainResidue
DILE108
DASN112
DASP218
DLEU221
DGLY222
DTYR258
DMET311
DALA312
DUMP314
DHOH443
DPHE80

Functional Information from PROSITE/UniProt
site_idPS00091
Number of Residues29
DetailsTHYMIDYLATE_SYNTHASE Thymidylate synthase active site. RriImcaWNprdlplma.....LpPCHalcQFyV
ChainResidueDetails
AARG175-VAL203

Functional Information from SwissProt/UniProt
site_idSWS_FT_FI1
Number of Residues4
DetailsACT_SITE: Nucleophile => ECO:0000250|UniProtKB:P0A884
ChainResidueDetails
ACYS195
BCYS195
CCYS195
DCYS195

site_idSWS_FT_FI2
Number of Residues8
DetailsBINDING: in other chain => ECO:0000250|UniProtKB:P0A884
ChainResidueDetails
AARG50
AASN226
BARG50
BASN226
CARG50
CASN226
DARG50
DASN226

site_idSWS_FT_FI3
Number of Residues4
DetailsBINDING: BINDING => ECO:0000250|UniProtKB:P45352
ChainResidueDetails
AARG175
BARG175
CARG175
DARG175

site_idSWS_FT_FI4
Number of Residues12
DetailsBINDING: in other chain => ECO:0000250|UniProtKB:P45352
ChainResidueDetails
ACYS195
DCYS195
DARG215
DHIS256
AARG215
AHIS256
BCYS195
BARG215
BHIS256
CCYS195
CARG215
CHIS256

site_idSWS_FT_FI5
Number of Residues8
DetailsBINDING: BINDING => ECO:0000250|UniProtKB:P0A884
ChainResidueDetails
AASP218
AALA312
BASP218
BALA312
CASP218
CALA312
DASP218
DALA312

site_idSWS_FT_FI6
Number of Residues4
DetailsMOD_RES: Phosphoserine => ECO:0007744|PubMed:19690332, ECO:0007744|PubMed:23186163
ChainResidueDetails
ASER114
BSER114
CSER114
DSER114

site_idSWS_FT_FI7
Number of Residues16
DetailsCROSSLNK: Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO2) => ECO:0007744|PubMed:28112733
ChainResidueDetails
ALYS287
CLYS292
CLYS308
DLYS287
DLYS292
DLYS308
ALYS292
ALYS308
BLYS287
BLYS292
BLYS308
CLYS287

Catalytic Information from CSA
site_idCSA1
Number of Residues6
DetailsAnnotated By Reference To The Literature 1b02
ChainResidueDetails
AASP254
ASER216
ACYS195
AASP218
AGLU87
AHIS256

site_idCSA2
Number of Residues6
DetailsAnnotated By Reference To The Literature 1b02
ChainResidueDetails
BASP254
BSER216
BCYS195
BASP218
BGLU87
BHIS256

site_idCSA3
Number of Residues6
DetailsAnnotated By Reference To The Literature 1b02
ChainResidueDetails
CASP254
CSER216
CCYS195
CASP218
CGLU87
CHIS256

site_idCSA4
Number of Residues6
DetailsAnnotated By Reference To The Literature 1b02
ChainResidueDetails
DASP254
DSER216
DCYS195
DASP218
DGLU87
DHIS256

site_idCSA5
Number of Residues3
DetailsAnnotated By Reference To The Literature 1b02
ChainResidueDetails
AASN226
ASER229
ACYS195

site_idCSA6
Number of Residues3
DetailsAnnotated By Reference To The Literature 1b02
ChainResidueDetails
BASN226
BSER229
BCYS195

site_idCSA7
Number of Residues3
DetailsAnnotated By Reference To The Literature 1b02
ChainResidueDetails
CASN226
CSER229
CCYS195

site_idCSA8
Number of Residues3
DetailsAnnotated By Reference To The Literature 1b02
ChainResidueDetails
DASN226
DSER229
DCYS195

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PDB entries from 2024-07-10

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