TYSY_PNECA
ID TYSY_PNECA Reviewed; 297 AA.
AC P13100;
DT 01-JAN-1990, integrated into UniProtKB/Swiss-Prot.
DT 01-JAN-1990, sequence version 1.
DT 03-AUG-2022, entry version 105.
DE RecName: Full=Thymidylate synthase;
DE Short=TS;
DE Short=TSase;
DE EC=2.1.1.45;
GN Name=THYA;
OS Pneumocystis carinii.
OC Eukaryota; Fungi; Dikarya; Ascomycota; Taphrinomycotina;
OC Pneumocystidomycetes; Pneumocystidaceae; Pneumocystis.
OX NCBI_TaxID=4754;
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RX PubMed=2671992; DOI=10.1073/pnas.86.17.6503;
RA Edman U., Edman J.C., Lundgren B., Santi D.V.;
RT "Isolation and expression of the Pneumocystis carinii thymidylate synthase
RT gene.";
RL Proc. Natl. Acad. Sci. U.S.A. 86:6503-6507(1989).
RN [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 112-210.
RX PubMed=7728138; DOI=10.1111/j.1550-7408.1995.tb01536.x;
RA Mazars E., Odberg-Ferragut C., Dei-Cas E., Fourmaux M.N., Aliouat E.M.,
RA Brun-Pascaud M., Mougeot G., Camus D.;
RT "Polymorphism of the thymidylate synthase gene of Pneumocystis carinii from
RT different host species.";
RL J. Eukaryot. Microbiol. 42:26-32(1995).
RN [3]
RP X-RAY CRYSTALLOGRAPHY (2.6 ANGSTROMS).
RX PubMed=10529228; DOI=10.1021/bi991610i;
RA Anderson A.C., O'Neil R.H., DeLano W.L., Stroud R.M.;
RT "The structural mechanism for half-the-sites reactivity in an enzyme,
RT thymidylate synthase, involves a relay of changes between subunits.";
RL Biochemistry 38:13829-13836(1999).
CC -!- CATALYTIC ACTIVITY:
CC Reaction=(6R)-5,10-methylene-5,6,7,8-tetrahydrofolate + dUMP = 7,8-
CC dihydrofolate + dTMP; Xref=Rhea:RHEA:12104, ChEBI:CHEBI:15636,
CC ChEBI:CHEBI:57451, ChEBI:CHEBI:63528, ChEBI:CHEBI:246422;
CC EC=2.1.1.45;
CC -!- PATHWAY: Pyrimidine metabolism; dTTP biosynthesis.
CC -!- SUBUNIT: Homodimer.
CC -!- SIMILARITY: Belongs to the thymidylate synthase family. {ECO:0000305}.
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DR EMBL; M25415; AAA33802.1; -; Genomic_DNA.
DR EMBL; S77510; AAB34157.1; -; Genomic_DNA.
DR PIR; A33720; YXUNTP.
DR PDB; 1CI7; X-ray; 2.60 A; A/B=1-297.
DR PDB; 1F28; X-ray; 1.90 A; A/B/C/D=1-297.
DR PDBsum; 1CI7; -.
DR PDBsum; 1F28; -.
DR AlphaFoldDB; P13100; -.
DR SMR; P13100; -.
DR BindingDB; P13100; -.
DR ChEMBL; CHEMBL3085612; -.
DR DrugBank; DB03541; 10-Propargyl-5,8-Dideazafolic Acid.
DR DrugBank; DB03800; Deoxyuridine monophosphate.
DR BRENDA; 2.1.1.45; 4924.
DR UniPathway; UPA00575; -.
DR EvolutionaryTrace; P13100; -.
DR GO; GO:0004799; F:thymidylate synthase activity; IEA:UniProtKB-EC.
DR GO; GO:0006231; P:dTMP biosynthetic process; IEA:InterPro.
DR GO; GO:0006235; P:dTTP biosynthetic process; IEA:UniProtKB-UniPathway.
DR GO; GO:0032259; P:methylation; IEA:UniProtKB-KW.
DR CDD; cd00351; TS_Pyrimidine_HMase; 1.
DR Gene3D; 3.30.572.10; -; 1.
DR HAMAP; MF_00008; Thymidy_synth_bact; 1.
DR InterPro; IPR045097; Thymidate_synth/dCMP_Mease.
DR InterPro; IPR023451; Thymidate_synth/dCMP_Mease_dom.
DR InterPro; IPR036926; Thymidate_synth/dCMP_Mease_sf.
DR InterPro; IPR000398; Thymidylate_synthase.
DR InterPro; IPR020940; Thymidylate_synthase_AS.
DR PANTHER; PTHR11548; PTHR11548; 1.
DR Pfam; PF00303; Thymidylat_synt; 1.
DR PRINTS; PR00108; THYMDSNTHASE.
DR SUPFAM; SSF55831; SSF55831; 1.
DR TIGRFAMs; TIGR03284; thym_sym; 1.
DR PROSITE; PS00091; THYMIDYLATE_SYNTHASE; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Methyltransferase; Nucleotide biosynthesis; Transferase.
FT CHAIN 1..297
FT /note="Thymidylate synthase"
FT /id="PRO_0000140911"
FT ACT_SITE 173
FT /note="Nucleophile"
FT /evidence="ECO:0000250|UniProtKB:P0A884"
FT BINDING 26
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:0000250|UniProtKB:P0A884"
FT BINDING 153..154
FT /ligand="dUMP"
FT /ligand_id="ChEBI:CHEBI:246422"
FT /ligand_note="ligand shared between dimeric partners"
FT /evidence="ECO:0000250|UniProtKB:P0A884"
FT BINDING 199..202
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:0000250|UniProtKB:P0A884"
FT BINDING 202
FT /ligand="(6R)-5,10-methylene-5,6,7,8-tetrahydrofolate"
FT /ligand_id="ChEBI:CHEBI:15636"
FT /evidence="ECO:0000250|UniProtKB:P0A884"
FT BINDING 210
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:0000250|UniProtKB:P0A884"
FT BINDING 240..242
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:0000250|UniProtKB:P0A884"
FT HELIX 4..19
FT /evidence="ECO:0007829|PDB:1F28"
FT STRAND 21..24
FT /evidence="ECO:0007829|PDB:1F28"
FT STRAND 28..36
FT /evidence="ECO:0007829|PDB:1F28"
FT STRAND 40..43
FT /evidence="ECO:0007829|PDB:1F28"
FT HELIX 45..47
FT /evidence="ECO:0007829|PDB:1F28"
FT STRAND 53..55
FT /evidence="ECO:0007829|PDB:1F28"
FT HELIX 59..70
FT /evidence="ECO:0007829|PDB:1F28"
FT HELIX 76..80
FT /evidence="ECO:0007829|PDB:1F28"
FT TURN 81..83
FT /evidence="ECO:0007829|PDB:1F28"
FT HELIX 88..91
FT /evidence="ECO:0007829|PDB:1F28"
FT HELIX 93..98
FT /evidence="ECO:0007829|PDB:1F28"
FT HELIX 113..119
FT /evidence="ECO:0007829|PDB:1F28"
FT HELIX 138..148
FT /evidence="ECO:0007829|PDB:1F28"
FT STRAND 156..158
FT /evidence="ECO:0007829|PDB:1F28"
FT TURN 162..164
FT /evidence="ECO:0007829|PDB:1F28"
FT HELIX 165..167
FT /evidence="ECO:0007829|PDB:1F28"
FT STRAND 168..170
FT /evidence="ECO:0007829|PDB:1F28"
FT STRAND 173..181
FT /evidence="ECO:0007829|PDB:1F28"
FT STRAND 191..202
FT /evidence="ECO:0007829|PDB:1F28"
FT TURN 203..205
FT /evidence="ECO:0007829|PDB:1F28"
FT HELIX 206..224
FT /evidence="ECO:0007829|PDB:1F28"
FT STRAND 228..242
FT /evidence="ECO:0007829|PDB:1F28"
FT HELIX 243..250
FT /evidence="ECO:0007829|PDB:1F28"
FT HELIX 252..254
FT /evidence="ECO:0007829|PDB:1F28"
FT STRAND 262..265
FT /evidence="ECO:0007829|PDB:1F28"
FT HELIX 272..274
FT /evidence="ECO:0007829|PDB:1F28"
FT HELIX 277..279
FT /evidence="ECO:0007829|PDB:1F28"
FT STRAND 280..284
FT /evidence="ECO:0007829|PDB:1F28"
SQ SEQUENCE 297 AA; 34362 MW; 985F6F870EF2A7B2 CRC64;
MVNAEEQQYL NLVQYIINHG EDRPDRTGTG TLSVFAPSPL KFSLRNKTFP LLTTKRVFIR
GVIEELLWFI RGETDSLKLR EKNIHIWDAN GSREYLDSIG LTKRQEGDLG PIYGFQWRHF
GAEYIDCKTN YIGQGVDQLA NIIQKIRTSP YDRRLILSAW NPADLEKMAL PPCHMFCQFY
VHIPSNNHRP ELSCQLYQRS CDMGLGVPFN IASYALLTCM IAHVCDLDPG DFIHVMGDCH
IYKDHIEALQ QQLTRSPRPF PTLSLNRSIT DIEDFTLDDF NIQNYHPYET IKMKMSI
