THYX_HELPY
ID THYX_HELPY Reviewed; 208 AA.
AC O26061;
DT 11-JUL-2001, integrated into UniProtKB/Swiss-Prot.
DT 11-JUL-2001, sequence version 2.
DT 03-AUG-2022, entry version 127.
DE RecName: Full=Flavin-dependent thymidylate synthase {ECO:0000303|PubMed:12029065};
DE Short=FDTS {ECO:0000255|HAMAP-Rule:MF_01408};
DE EC=2.1.1.148 {ECO:0000269|PubMed:12029065};
DE AltName: Full=FAD-dependent thymidylate synthase {ECO:0000255|HAMAP-Rule:MF_01408};
DE AltName: Full=Thymidylate synthase ThyX {ECO:0000303|PubMed:12029065};
DE Short=TS {ECO:0000255|HAMAP-Rule:MF_01408};
DE Short=TSase {ECO:0000255|HAMAP-Rule:MF_01408};
GN Name=thyX {ECO:0000303|PubMed:12029065}; OrderedLocusNames=HP_1533;
OS Helicobacter pylori (strain ATCC 700392 / 26695) (Campylobacter pylori).
OC Bacteria; Proteobacteria; Epsilonproteobacteria; Campylobacterales;
OC Helicobacteraceae; Helicobacter.
OX NCBI_TaxID=85962;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=ATCC 700392 / 26695;
RX PubMed=9252185; DOI=10.1038/41483;
RA Tomb J.-F., White O., Kerlavage A.R., Clayton R.A., Sutton G.G.,
RA Fleischmann R.D., Ketchum K.A., Klenk H.-P., Gill S.R., Dougherty B.A.,
RA Nelson K.E., Quackenbush J., Zhou L., Kirkness E.F., Peterson S.N.,
RA Loftus B.J., Richardson D.L., Dodson R.J., Khalak H.G., Glodek A.,
RA McKenney K., FitzGerald L.M., Lee N., Adams M.D., Hickey E.K., Berg D.E.,
RA Gocayne J.D., Utterback T.R., Peterson J.D., Kelley J.M., Cotton M.D.,
RA Weidman J.F., Fujii C., Bowman C., Watthey L., Wallin E., Hayes W.S.,
RA Borodovsky M., Karp P.D., Smith H.O., Fraser C.M., Venter J.C.;
RT "The complete genome sequence of the gastric pathogen Helicobacter
RT pylori.";
RL Nature 388:539-547(1997).
RN [2]
RP FUNCTION, CATALYTIC ACTIVITY, COFACTOR, SUBUNIT, AND MUTAGENESIS OF SER-84.
RX PubMed=12029065; DOI=10.1126/science.1072113;
RA Myllykallio H., Lipowski G., Leduc D., Filee J., Forterre P., Liebl U.;
RT "An alternative flavin-dependent mechanism for thymidylate synthesis.";
RL Science 297:105-107(2002).
RN [3]
RP X-RAY CRYSTALLOGRAPHY (2.50 ANGSTROMS) IN COMPLEX WITH FAD AND DUMP, AND
RP COFACTOR.
RC STRAIN=ATCC 700392 / 26695;
RX PubMed=22512654; DOI=10.2174/092986612803217105;
RA Zhang X., Zhang J., Guo G., Mao X., Hu Y., Zou Q.;
RT "Crystal structure of a flavin-dependent thymidylate synthase from
RT Helicobacter pylori strain 26695.";
RL Protein Pept. Lett. 19:1225-1230(2012).
CC -!- FUNCTION: Catalyzes the reductive methylation of 2'-deoxyuridine-5'-
CC monophosphate (dUMP) to 2'-deoxythymidine-5'-monophosphate (dTMP) while
CC utilizing 5,10-methylenetetrahydrofolate (mTHF) as the methyl donor,
CC and NAD(P)H and FADH(2) as the reductant.
CC {ECO:0000269|PubMed:12029065}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=(6R)-5,10-methylene-5,6,7,8-tetrahydrofolate + dUMP + H(+) +
CC NADPH = (6S)-5,6,7,8-tetrahydrofolate + dTMP + NADP(+);
CC Xref=Rhea:RHEA:29043, ChEBI:CHEBI:15378, ChEBI:CHEBI:15636,
CC ChEBI:CHEBI:57453, ChEBI:CHEBI:57783, ChEBI:CHEBI:58349,
CC ChEBI:CHEBI:63528, ChEBI:CHEBI:246422; EC=2.1.1.148;
CC Evidence={ECO:0000269|PubMed:12029065};
CC -!- COFACTOR:
CC Name=FAD; Xref=ChEBI:CHEBI:57692;
CC Evidence={ECO:0000269|PubMed:22512654, ECO:0000305|PubMed:12029065};
CC Note=Binds 4 FAD per tetramer. Each FAD binding site is formed by three
CC monomers. {ECO:0000269|PubMed:22512654};
CC -!- PATHWAY: Pyrimidine metabolism; dTTP biosynthesis. {ECO:0000255|HAMAP-
CC Rule:MF_01408}.
CC -!- SUBUNIT: Homotetramer. {ECO:0000269|PubMed:12029065}.
CC -!- MISCELLANEOUS: ThyX activity is mechanistically distinct from ThyA
CC activity.
CC -!- SIMILARITY: Belongs to the thymidylate synthase ThyX family.
CC {ECO:0000255|HAMAP-Rule:MF_01408}.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAD08571.1; Type=Erroneous initiation; Note=Extended N-terminus.; Evidence={ECO:0000305};
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DR EMBL; AE000511; AAD08571.1; ALT_INIT; Genomic_DNA.
DR PIR; E64711; E64711.
DR RefSeq; NP_208323.1; NC_000915.1.
DR RefSeq; WP_000451918.1; NC_000915.1.
DR PDB; 3AH5; X-ray; 2.50 A; A/B/C/D/E/F=1-208.
DR PDBsum; 3AH5; -.
DR AlphaFoldDB; O26061; -.
DR SMR; O26061; -.
DR IntAct; O26061; 12.
DR MINT; O26061; -.
DR STRING; 85962.C694_07940; -.
DR PaxDb; O26061; -.
DR EnsemblBacteria; AAD08571; AAD08571; HP_1533.
DR KEGG; hpy:HP_1533; -.
DR PATRIC; fig|85962.47.peg.1648; -.
DR eggNOG; COG1351; Bacteria.
DR OMA; CWQSFDK; -.
DR PhylomeDB; O26061; -.
DR BioCyc; MetaCyc:MON-15768; -.
DR BRENDA; 2.1.1.148; 2604.
DR BRENDA; 2.1.1.45; 2604.
DR UniPathway; UPA00575; -.
DR EvolutionaryTrace; O26061; -.
DR Proteomes; UP000000429; Chromosome.
DR GO; GO:0050660; F:flavin adenine dinucleotide binding; IBA:GO_Central.
DR GO; GO:0070402; F:NADPH binding; IBA:GO_Central.
DR GO; GO:0050797; F:thymidylate synthase (FAD) activity; IBA:GO_Central.
DR GO; GO:0004799; F:thymidylate synthase activity; IBA:GO_Central.
DR GO; GO:0006231; P:dTMP biosynthetic process; IBA:GO_Central.
DR GO; GO:0006235; P:dTTP biosynthetic process; IEA:UniProtKB-UniPathway.
DR GO; GO:0032259; P:methylation; IEA:UniProtKB-KW.
DR Gene3D; 3.30.1360.170; -; 1.
DR HAMAP; MF_01408; ThyX; 1.
DR InterPro; IPR003669; Thymidylate_synthase_ThyX.
DR InterPro; IPR036098; Thymidylate_synthase_ThyX_sf.
DR PANTHER; PTHR34934; PTHR34934; 1.
DR Pfam; PF02511; Thy1; 1.
DR SUPFAM; SSF69796; SSF69796; 1.
DR TIGRFAMs; TIGR02170; thyX; 1.
DR PROSITE; PS51331; THYX; 1.
PE 1: Evidence at protein level;
KW 3D-structure; FAD; Flavoprotein; Methyltransferase; NADP;
KW Nucleotide biosynthesis; Reference proteome; Transferase.
FT CHAIN 1..208
FT /note="Flavin-dependent thymidylate synthase"
FT /id="PRO_0000175566"
FT DOMAIN 1..208
FT /note="ThyX"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00661"
FT MOTIF 74..84
FT /note="ThyX motif"
FT /evidence="ECO:0000305|PubMed:12029065"
FT ACT_SITE 174
FT /note="Involved in ionization of N3 of dUMP, leading to its
FT activation"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_01408"
FT BINDING 50
FT /ligand="FAD"
FT /ligand_id="ChEBI:CHEBI:57692"
FT /ligand_note="ligand shared between neighboring subunits"
FT /evidence="ECO:0000269|PubMed:22512654,
FT ECO:0007744|PDB:3AH5"
FT BINDING 71..74
FT /ligand="dUMP"
FT /ligand_id="ChEBI:CHEBI:246422"
FT /ligand_note="ligand shared between dimeric partners"
FT /evidence="ECO:0000269|PubMed:22512654,
FT ECO:0007744|PDB:3AH5"
FT BINDING 74..76
FT /ligand="FAD"
FT /ligand_id="ChEBI:CHEBI:57692"
FT /ligand_note="ligand shared between neighboring subunits"
FT /evidence="ECO:0000269|PubMed:22512654,
FT ECO:0007744|PDB:3AH5"
FT BINDING 84..86
FT /ligand="dUMP"
FT /ligand_id="ChEBI:CHEBI:246422"
FT /ligand_note="ligand shared between dimeric partners"
FT /note="in other chain"
FT /evidence="ECO:0000269|PubMed:22512654,
FT ECO:0007744|PDB:3AH5"
FT BINDING 147
FT /ligand="dUMP"
FT /ligand_id="ChEBI:CHEBI:246422"
FT /ligand_note="ligand shared between dimeric partners"
FT /note="in other chain"
FT /evidence="ECO:0000269|PubMed:22512654"
FT BINDING 163..165
FT /ligand="FAD"
FT /ligand_id="ChEBI:CHEBI:57692"
FT /ligand_note="ligand shared between neighboring subunits"
FT /evidence="ECO:0000269|PubMed:22512654,
FT ECO:0007744|PDB:3AH5"
FT BINDING 169
FT /ligand="FAD"
FT /ligand_id="ChEBI:CHEBI:57692"
FT /ligand_note="ligand shared between neighboring subunits"
FT /evidence="ECO:0000269|PubMed:22512654,
FT ECO:0007744|PDB:3AH5"
FT BINDING 174
FT /ligand="dUMP"
FT /ligand_id="ChEBI:CHEBI:246422"
FT /ligand_note="ligand shared between dimeric partners"
FT /evidence="ECO:0000269|PubMed:22512654,
FT ECO:0007744|PDB:3AH5"
FT MUTAGEN 84
FT /note="S->A: Abolishes complementation when expressed in an
FT E.coli thyA deletion mutant."
FT /evidence="ECO:0000269|PubMed:12029065"
FT STRAND 2..8
FT /evidence="ECO:0007829|PDB:3AH5"
FT HELIX 12..22
FT /evidence="ECO:0007829|PDB:3AH5"
FT HELIX 25..27
FT /evidence="ECO:0007829|PDB:3AH5"
FT STRAND 30..32
FT /evidence="ECO:0007829|PDB:3AH5"
FT HELIX 33..43
FT /evidence="ECO:0007829|PDB:3AH5"
FT HELIX 46..54
FT /evidence="ECO:0007829|PDB:3AH5"
FT STRAND 56..65
FT /evidence="ECO:0007829|PDB:3AH5"
FT HELIX 66..72
FT /evidence="ECO:0007829|PDB:3AH5"
FT STRAND 77..82
FT /evidence="ECO:0007829|PDB:3AH5"
FT HELIX 85..88
FT /evidence="ECO:0007829|PDB:3AH5"
FT HELIX 89..92
FT /evidence="ECO:0007829|PDB:3AH5"
FT HELIX 103..109
FT /evidence="ECO:0007829|PDB:3AH5"
FT TURN 110..112
FT /evidence="ECO:0007829|PDB:3AH5"
FT HELIX 119..137
FT /evidence="ECO:0007829|PDB:3AH5"
FT HELIX 143..146
FT /evidence="ECO:0007829|PDB:3AH5"
FT HELIX 147..149
FT /evidence="ECO:0007829|PDB:3AH5"
FT STRAND 154..163
FT /evidence="ECO:0007829|PDB:3AH5"
FT HELIX 164..174
FT /evidence="ECO:0007829|PDB:3AH5"
FT HELIX 181..193
FT /evidence="ECO:0007829|PDB:3AH5"
FT TURN 196..198
FT /evidence="ECO:0007829|PDB:3AH5"
FT HELIX 199..201
FT /evidence="ECO:0007829|PDB:3AH5"
FT HELIX 203..205
FT /evidence="ECO:0007829|PDB:3AH5"
FT TURN 206..208
FT /evidence="ECO:0007829|PDB:3AH5"
SQ SEQUENCE 208 AA; 24071 MW; 88FF23ED4B26283C CRC64;
MEVICKHYTP LDIASQAIRT CWQSFEYSDD GGCKDKELIH RVGNIFRHSS TLEHLYYNFE
IKGLSRGALQ ELSRHRIASL SVKSSRYTLR ELKEVESFLP LNETNLERAK EFLVFVDNEK
VNAMSVLALE NLRILLSEHN IKNDLAKYAM PESYKTHLAY SINARSLQNF LTLRSSNKAL
KEMQDLAKAL FDALPGEHQY LFEDCLKH
