THIC_SALTY
ID THIC_SALTY Reviewed; 631 AA.
AC Q9L9I7;
DT 29-AUG-2001, integrated into UniProtKB/Swiss-Prot.
DT 01-OCT-2000, sequence version 1.
DT 03-AUG-2022, entry version 112.
DE RecName: Full=Phosphomethylpyrimidine synthase;
DE EC=4.1.99.17 {ECO:0000269|PubMed:18686975};
DE AltName: Full=Hydroxymethylpyrimidine phosphate synthase;
DE Short=HMP-P synthase;
DE Short=HMP-phosphate synthase;
DE Short=HMPP synthase;
DE AltName: Full=Thiamine biosynthesis protein ThiC;
GN Name=thiC; OrderedLocusNames=STM4164; ORFNames=STMF1.33;
OS Salmonella typhimurium (strain LT2 / SGSC1412 / ATCC 700720).
OC Bacteria; Proteobacteria; Gammaproteobacteria; Enterobacterales;
OC Enterobacteriaceae; Salmonella.
OX NCBI_TaxID=99287;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=LT2 / SGSC1412 / ATCC 700720;
RX PubMed=11677609; DOI=10.1038/35101614;
RA McClelland M., Sanderson K.E., Spieth J., Clifton S.W., Latreille P.,
RA Courtney L., Porwollik S., Ali J., Dante M., Du F., Hou S., Layman D.,
RA Leonard S., Nguyen C., Scott K., Holmes A., Grewal N., Mulvaney E.,
RA Ryan E., Sun H., Florea L., Miller W., Stoneking T., Nhan M., Waterston R.,
RA Wilson R.K.;
RT "Complete genome sequence of Salmonella enterica serovar Typhimurium LT2.";
RL Nature 413:852-856(2001).
RN [2]
RP PROTEIN SEQUENCE OF 437-443, PRESENCE OF AN S-ADENOSYL-L-METHIONINE
RP RADICAL, AND EPR SPECTROSCOPY.
RX PubMed=19113839; DOI=10.1021/bi802154j;
RA Martinez-Gomez N.C., Poyner R.R., Mansoorabadi S.O., Reed G.H., Downs D.M.;
RT "Reaction of AdoMet with ThiC generates a backbone free radical.";
RL Biochemistry 48:217-219(2009).
RN [3]
RP MUTAGENESIS OF GLU-324; CYS-363; PHE-371; ASN-405; ILE-485; CYS-494;
RP ARG-548; CYS-581; CYS-584 AND CYS-589.
RC STRAIN=LT2 / SGSC1412 / ATCC 700720;
RX PubMed=16849799; DOI=10.1099/mic.0.28926-0;
RA Dougherty M.J., Downs D.M.;
RT "A connection between iron-sulfur cluster metabolism and the biosynthesis
RT of 4-amino-5-hydroxymethyl-2-methylpyrimidine pyrophosphate in Salmonella
RT enterica.";
RL Microbiology 152:2345-2353(2006).
RN [4]
RP CATALYTIC ACTIVITY, COFACTOR, AND EPR SPECTROSCOPY.
RC STRAIN=LT2 / SGSC1412 / ATCC 700720;
RX PubMed=18686975; DOI=10.1021/bi8010253;
RA Martinez-Gomez N.C., Downs D.M.;
RT "ThiC is an [Fe-S] cluster protein that requires AdoMet to generate the 4-
RT amino-5-hydroxymethyl-2-methylpyrimidine moiety in thiamin synthesis.";
RL Biochemistry 47:9054-9056(2008).
CC -!- FUNCTION: Catalyzes the synthesis of the hydroxymethylpyrimidine
CC phosphate (HMP-P) moiety of thiamine from aminoimidazole ribotide (AIR)
CC in a radical S-adenosyl-L-methionine (SAM)-dependent reaction.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=5-amino-1-(5-phospho-beta-D-ribosyl)imidazole + S-adenosyl-L-
CC methionine = 4-amino-2-methyl-5-(phosphooxymethyl)pyrimidine + 5'-
CC deoxyadenosine + CO + formate + 3 H(+) + L-methionine;
CC Xref=Rhea:RHEA:24840, ChEBI:CHEBI:15378, ChEBI:CHEBI:15740,
CC ChEBI:CHEBI:17245, ChEBI:CHEBI:17319, ChEBI:CHEBI:57844,
CC ChEBI:CHEBI:58354, ChEBI:CHEBI:59789, ChEBI:CHEBI:137981;
CC EC=4.1.99.17; Evidence={ECO:0000269|PubMed:18686975};
CC -!- COFACTOR:
CC Name=[4Fe-4S] cluster; Xref=ChEBI:CHEBI:49883;
CC Evidence={ECO:0000269|PubMed:18686975};
CC Note=Binds 1 [4Fe-4S] cluster per subunit. The cluster is coordinated
CC with 3 cysteines and an exchangeable S-adenosyl-L-methionine.
CC {ECO:0000269|PubMed:18686975};
CC -!- PATHWAY: Cofactor biosynthesis; thiamine diphosphate biosynthesis.
CC -!- SUBUNIT: Homodimer. {ECO:0000250}.
CC -!- SIMILARITY: Belongs to the ThiC family. {ECO:0000305}.
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DR EMBL; AF170176; AAF33523.1; -; Genomic_DNA.
DR EMBL; AE006468; AAL22992.1; -; Genomic_DNA.
DR RefSeq; NP_463033.1; NC_003197.2.
DR RefSeq; WP_000108413.1; NC_003197.2.
DR AlphaFoldDB; Q9L9I7; -.
DR SMR; Q9L9I7; -.
DR STRING; 99287.STM4164; -.
DR PaxDb; Q9L9I7; -.
DR EnsemblBacteria; AAL22992; AAL22992; STM4164.
DR GeneID; 1255690; -.
DR KEGG; stm:STM4164; -.
DR PATRIC; fig|99287.12.peg.4378; -.
DR HOGENOM; CLU_013181_2_1_6; -.
DR OMA; TWELFRD; -.
DR PhylomeDB; Q9L9I7; -.
DR BioCyc; SENT99287:STM4164-MON; -.
DR BRENDA; 4.1.99.17; 2169.
DR UniPathway; UPA00060; -.
DR Proteomes; UP000001014; Chromosome.
DR GO; GO:0005829; C:cytosol; IBA:GO_Central.
DR GO; GO:0051539; F:4 iron, 4 sulfur cluster binding; IEA:UniProtKB-KW.
DR GO; GO:0070284; F:4-amino-5-hydroxymethyl-2-methylpyrimidine phosphate synthase activity; IDA:UniProtKB.
DR GO; GO:0016830; F:carbon-carbon lyase activity; IEA:InterPro.
DR GO; GO:0008270; F:zinc ion binding; IEA:UniProtKB-UniRule.
DR GO; GO:0009228; P:thiamine biosynthetic process; IDA:UniProtKB.
DR GO; GO:0009229; P:thiamine diphosphate biosynthetic process; IEA:UniProtKB-UniPathway.
DR Gene3D; 3.20.20.540; -; 1.
DR HAMAP; MF_00089; ThiC; 1.
DR InterPro; IPR037509; ThiC.
DR InterPro; IPR025747; ThiC-associated_dom.
DR InterPro; IPR038521; ThiC/Bza_core_dom.
DR InterPro; IPR002817; ThiC/BzaA/B.
DR PANTHER; PTHR30557; PTHR30557; 1.
DR Pfam; PF13667; ThiC-associated; 1.
DR Pfam; PF01964; ThiC_Rad_SAM; 1.
DR SFLD; SFLDF00407; phosphomethylpyrimidine_syntha; 1.
DR TIGRFAMs; TIGR00190; thiC; 1.
PE 1: Evidence at protein level;
KW 4Fe-4S; Direct protein sequencing; Iron; Iron-sulfur; Lyase; Metal-binding;
KW Reference proteome; S-adenosyl-L-methionine; Thiamine biosynthesis; Zinc.
FT CHAIN 1..631
FT /note="Phosphomethylpyrimidine synthase"
FT /id="PRO_0000152835"
FT BINDING 239
FT /ligand="substrate"
FT /evidence="ECO:0000250"
FT BINDING 268
FT /ligand="substrate"
FT /evidence="ECO:0000250"
FT BINDING 297
FT /ligand="substrate"
FT /evidence="ECO:0000250"
FT BINDING 333
FT /ligand="substrate"
FT /evidence="ECO:0000250"
FT BINDING 353..355
FT /ligand="substrate"
FT /evidence="ECO:0000250"
FT BINDING 394..397
FT /ligand="substrate"
FT /evidence="ECO:0000250"
FT BINDING 433
FT /ligand="substrate"
FT /evidence="ECO:0000250"
FT BINDING 437
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000250"
FT BINDING 460
FT /ligand="substrate"
FT /evidence="ECO:0000250"
FT BINDING 501
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000250"
FT BINDING 581
FT /ligand="[4Fe-4S] cluster"
FT /ligand_id="ChEBI:CHEBI:49883"
FT /ligand_note="4Fe-4S-S-AdoMet"
FT /evidence="ECO:0000250"
FT BINDING 584
FT /ligand="[4Fe-4S] cluster"
FT /ligand_id="ChEBI:CHEBI:49883"
FT /ligand_note="4Fe-4S-S-AdoMet"
FT /evidence="ECO:0000250"
FT BINDING 589
FT /ligand="[4Fe-4S] cluster"
FT /ligand_id="ChEBI:CHEBI:49883"
FT /ligand_note="4Fe-4S-S-AdoMet"
FT /evidence="ECO:0000250"
FT MUTAGEN 324
FT /note="E->K: Shows thiamine-independent growth under
FT anaerobic conditions, but thiamine dependent growth under
FT aerobic conditions."
FT /evidence="ECO:0000269|PubMed:16849799"
FT MUTAGEN 363
FT /note="C->M: No effect."
FT /evidence="ECO:0000269|PubMed:16849799"
FT MUTAGEN 371
FT /note="F->P: No effect."
FT /evidence="ECO:0000269|PubMed:16849799"
FT MUTAGEN 405
FT /note="N->S: No effect."
FT /evidence="ECO:0000269|PubMed:16849799"
FT MUTAGEN 485
FT /note="I->A: No effect."
FT /evidence="ECO:0000269|PubMed:16849799"
FT MUTAGEN 494
FT /note="C->A: No activity."
FT /evidence="ECO:0000269|PubMed:16849799"
FT MUTAGEN 548
FT /note="R->H: Shows thiamine-independent growth under
FT anaerobic conditions, but thiamine dependent growth under
FT aerobic conditions."
FT /evidence="ECO:0000269|PubMed:16849799"
FT MUTAGEN 581
FT /note="C->A: No activity."
FT /evidence="ECO:0000269|PubMed:16849799"
FT MUTAGEN 584
FT /note="C->A: No activity."
FT /evidence="ECO:0000269|PubMed:16849799"
FT MUTAGEN 589
FT /note="C->A: No activity."
FT /evidence="ECO:0000269|PubMed:16849799"
SQ SEQUENCE 631 AA; 70845 MW; 0A298124EC664A4A CRC64;
MSTTTLTRRE QRAKAQHFID TLEGTAFPNS KRIYVTGSQH DIRVPMREIQ LSPTLIGGSK
DNPQFEENEA VPVYDTSGPY GDPEVAINVQ QGLAKLRQPW IDARNDSEEL DDRSSAYTRE
RLADDGLDDL RFTGLLTPKR AKAGKRVTQL HYARKGIVTP EMEFIAIREN MGRERIRSEV
LRHQHPGMNF GARLPENITP EFVRDEVAAG RAIIPANINH PESEPMIIGR NFLVKVNANI
GNSAVTSSIE EEVEKLVWST RWGADTVMDL STGRYIHETR EWILRNSPVP IGTVPIYQAL
EKVNGIAEDL TWEAFRDTLL EQAEQGVDYF TIHAGVLLRY VPMTAKRLTG IVSRGGSIMA
KWCLSHHKEN FLFEHFREIC EICAAYDVSL SLGDGLRPGS IQDANDEAQF SELHTLGELT
KIAWEYDVQV MIEGPGHVPM HMIQRNMTEE LESCHEAPFY TLGPLTTDIA PGYDHFTSGI
GAAMIGWFGC AMLCYVTPKE HLGLPNKEDV KQGLITYKIA AHAADLAKGH PGAQIRDNAM
SKARFEFRWE DQFNLALDPF TARAYHDETL PQESGKVAHF CSMCGPKFCS MKISQEVRDY
AAAQTIEIGM ADMSEDFRAK GGEIYLKREE A
