THIC_CAUVC
ID THIC_CAUVC Reviewed; 612 AA.
AC Q9A6Q5;
DT 01-NOV-2002, integrated into UniProtKB/Swiss-Prot.
DT 01-JUN-2001, sequence version 1.
DT 03-AUG-2022, entry version 110.
DE RecName: Full=Phosphomethylpyrimidine synthase;
DE EC=4.1.99.17 {ECO:0000269|PubMed:18953358, ECO:0000269|PubMed:20886485};
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=CC_2029;
OS Caulobacter vibrioides (strain ATCC 19089 / CB15) (Caulobacter crescentus).
OC Bacteria; Proteobacteria; Alphaproteobacteria; Caulobacterales;
OC Caulobacteraceae; Caulobacter.
OX NCBI_TaxID=190650;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=ATCC 19089 / CB15;
RX PubMed=11259647; DOI=10.1073/pnas.061029298;
RA Nierman W.C., Feldblyum T.V., Laub M.T., Paulsen I.T., Nelson K.E.,
RA Eisen J.A., Heidelberg J.F., Alley M.R.K., Ohta N., Maddock J.R.,
RA Potocka I., Nelson W.C., Newton A., Stephens C., Phadke N.D., Ely B.,
RA DeBoy R.T., Dodson R.J., Durkin A.S., Gwinn M.L., Haft D.H., Kolonay J.F.,
RA Smit J., Craven M.B., Khouri H.M., Shetty J., Berry K.J., Utterback T.R.,
RA Tran K., Wolf A.M., Vamathevan J.J., Ermolaeva M.D., White O.,
RA Salzberg S.L., Venter J.C., Shapiro L., Fraser C.M.;
RT "Complete genome sequence of Caulobacter crescentus.";
RL Proc. Natl. Acad. Sci. U.S.A. 98:4136-4141(2001).
RN [2]
RP CATALYTIC ACTIVITY, AND REACTION MECHANISM.
RX PubMed=20886485; DOI=10.1002/anie.201003419;
RA Chatterjee A., Hazra A.B., Abdelwahed S., Hilmey D.G., Begley T.P.;
RT "A 'radical dance' in thiamin biosynthesis: mechanistic analysis of the
RT bacterial hydroxymethylpyrimidine phosphate synthase.";
RL Angew. Chem. Int. Ed. 49:8653-8656(2010).
RN [3] {ECO:0007744|PDB:3EPM, ECO:0007744|PDB:3EPN, ECO:0007744|PDB:3EPO}
RP X-RAY CRYSTALLOGRAPHY (2.10 ANGSTROMS) IN COMPLEXES WITH SUBSTRATE AND
RP ZINC, FUNCTION, CATALYTIC ACTIVITY, EPR SPECTROSCOPY, MOSSBAUER
RP SPECTROSCOPY, COFACTOR, AND SUBUNIT.
RX PubMed=18953358; DOI=10.1038/nchembio.121;
RA Chatterjee A., Li Y., Zhang Y., Grove T.L., Lee M., Krebs C., Booker S.J.,
RA Begley T.P., Ealick S.E.;
RT "Reconstitution of ThiC in thiamine pyrimidine biosynthesis expands the
RT radical SAM superfamily.";
RL Nat. Chem. Biol. 4:758-765(2008).
RN [4]
RP X-RAY CRYSTALLOGRAPHY (2.93 ANGSTROMS) IN COMPLEX WITH IRON-SULFUR
RP (4FE-4S), COFACTOR, AND MUTAGENESIS OF HIS-417 AND HIS-481.
RX PubMed=25813242; DOI=10.1038/ncomms7480;
RA Fenwick M.K., Mehta A.P., Zhang Y., Abdelwahed S.H., Begley T.P.,
RA Ealick S.E.;
RT "Non-canonical active site architecture of the radical SAM thiamin
RT pyrimidine synthase.";
RL Nat. Commun. 6:6480-6480(2015).
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 {ECO:0000269|PubMed:18953358}.
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:18953358,
CC ECO:0000269|PubMed:20886485};
CC -!- COFACTOR:
CC Name=[4Fe-4S] cluster; Xref=ChEBI:CHEBI:49883;
CC Evidence={ECO:0000269|PubMed:18953358, ECO:0000269|PubMed:25813242};
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:18953358, ECO:0000269|PubMed:25813242};
CC -!- PATHWAY: Cofactor biosynthesis; thiamine diphosphate biosynthesis.
CC -!- SUBUNIT: Homodimer. {ECO:0000269|PubMed:18953358}.
CC -!- SIMILARITY: Belongs to the ThiC family. {ECO:0000305}.
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DR EMBL; AE005673; AAK24004.1; -; Genomic_DNA.
DR PIR; H87500; H87500.
DR RefSeq; NP_420836.1; NC_002696.2.
DR RefSeq; WP_010919895.1; NC_002696.2.
DR PDB; 3EPM; X-ray; 2.79 A; A/B=1-612.
DR PDB; 3EPN; X-ray; 2.11 A; A/B=1-612.
DR PDB; 3EPO; X-ray; 2.10 A; A/B=1-612.
DR PDB; 4S2A; X-ray; 2.93 A; A=1-612.
DR PDBsum; 3EPM; -.
DR PDBsum; 3EPN; -.
DR PDBsum; 3EPO; -.
DR PDBsum; 4S2A; -.
DR AlphaFoldDB; Q9A6Q5; -.
DR SMR; Q9A6Q5; -.
DR STRING; 190650.CC_2029; -.
DR EnsemblBacteria; AAK24004; AAK24004; CC_2029.
DR KEGG; ccr:CC_2029; -.
DR PATRIC; fig|190650.5.peg.2049; -.
DR eggNOG; COG0422; Bacteria.
DR HOGENOM; CLU_013181_2_1_5; -.
DR OMA; TWELFRD; -.
DR BioCyc; CAULO:CC2029-MON; -.
DR BioCyc; MetaCyc:MON-14897; -.
DR BRENDA; 4.1.99.17; 1218.
DR UniPathway; UPA00060; -.
DR EvolutionaryTrace; Q9A6Q5; -.
DR Proteomes; UP000001816; Chromosome.
DR GO; GO:0051539; F:4 iron, 4 sulfur cluster binding; IDA:UniProtKB.
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 3D-structure; 4Fe-4S; Iron; Iron-sulfur; Lyase; Metal-binding;
KW Reference proteome; S-adenosyl-L-methionine; Thiamine biosynthesis; Zinc.
FT CHAIN 1..612
FT /note="Phosphomethylpyrimidine synthase"
FT /id="PRO_0000152793"
FT BINDING 219
FT /ligand="substrate"
FT /evidence="ECO:0000269|PubMed:18953358,
FT ECO:0007744|PDB:3EPN"
FT BINDING 248
FT /ligand="substrate"
FT /evidence="ECO:0000269|PubMed:18953358,
FT ECO:0007744|PDB:3EPN"
FT BINDING 277
FT /ligand="substrate"
FT /evidence="ECO:0000269|PubMed:18953358,
FT ECO:0007744|PDB:3EPN"
FT BINDING 313
FT /ligand="substrate"
FT /evidence="ECO:0000269|PubMed:18953358,
FT ECO:0007744|PDB:3EPN"
FT BINDING 333..335
FT /ligand="substrate"
FT /evidence="ECO:0000269|PubMed:18953358,
FT ECO:0007744|PDB:3EPN"
FT BINDING 374..377
FT /ligand="substrate"
FT /evidence="ECO:0000269|PubMed:18953358,
FT ECO:0007744|PDB:3EPN"
FT BINDING 413
FT /ligand="substrate"
FT /evidence="ECO:0000269|PubMed:18953358,
FT ECO:0007744|PDB:3EPN"
FT BINDING 417
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000269|PubMed:18953358,
FT ECO:0007744|PDB:3EPM"
FT BINDING 440
FT /ligand="substrate"
FT /evidence="ECO:0000269|PubMed:18953358,
FT ECO:0007744|PDB:3EPN"
FT BINDING 481
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000269|PubMed:18953358,
FT ECO:0007744|PDB:3EPM"
FT BINDING 561
FT /ligand="[4Fe-4S] cluster"
FT /ligand_id="ChEBI:CHEBI:49883"
FT /ligand_note="4Fe-4S-S-AdoMet"
FT /evidence="ECO:0000269|PubMed:25813242,
FT ECO:0007744|PDB:4S2A"
FT BINDING 564
FT /ligand="[4Fe-4S] cluster"
FT /ligand_id="ChEBI:CHEBI:49883"
FT /ligand_note="4Fe-4S-S-AdoMet"
FT /evidence="ECO:0000269|PubMed:25813242,
FT ECO:0007744|PDB:4S2A"
FT BINDING 569
FT /ligand="[4Fe-4S] cluster"
FT /ligand_id="ChEBI:CHEBI:49883"
FT /ligand_note="4Fe-4S-S-AdoMet"
FT /evidence="ECO:0000269|PubMed:25813242,
FT ECO:0007744|PDB:4S2A"
FT MUTAGEN 417
FT /note="H->A: 5-fold reduction in catalytic activity."
FT /evidence="ECO:0000269|PubMed:25813242"
FT MUTAGEN 481
FT /note="H->A: 5-fold reduction in catalytic activity."
FT /evidence="ECO:0000269|PubMed:25813242"
FT HELIX 6..13
FT /evidence="ECO:0007829|PDB:3EPO"
FT STRAND 23..28
FT /evidence="ECO:0007829|PDB:3EPO"
FT STRAND 30..32
FT /evidence="ECO:0007829|PDB:3EPO"
FT STRAND 36..42
FT /evidence="ECO:0007829|PDB:3EPO"
FT HELIX 46..48
FT /evidence="ECO:0007829|PDB:3EPO"
FT STRAND 53..55
FT /evidence="ECO:0007829|PDB:3EPO"
FT HELIX 60..63
FT /evidence="ECO:0007829|PDB:3EPO"
FT TURN 71..73
FT /evidence="ECO:0007829|PDB:3EPO"
FT HELIX 80..85
FT /evidence="ECO:0007829|PDB:3EPO"
FT STRAND 89..91
FT /evidence="ECO:0007829|PDB:3EPO"
FT HELIX 100..103
FT /evidence="ECO:0007829|PDB:4S2A"
FT HELIX 108..110
FT /evidence="ECO:0007829|PDB:4S2A"
FT STRAND 123..125
FT /evidence="ECO:0007829|PDB:3EPO"
FT HELIX 133..138
FT /evidence="ECO:0007829|PDB:3EPO"
FT HELIX 144..154
FT /evidence="ECO:0007829|PDB:3EPO"
FT STRAND 159..161
FT /evidence="ECO:0007829|PDB:3EPO"
FT HELIX 180..188
FT /evidence="ECO:0007829|PDB:3EPO"
FT STRAND 191..193
FT /evidence="ECO:0007829|PDB:3EPO"
FT STRAND 215..220
FT /evidence="ECO:0007829|PDB:3EPO"
FT HELIX 229..241
FT /evidence="ECO:0007829|PDB:3EPO"
FT STRAND 245..249
FT /evidence="ECO:0007829|PDB:3EPO"
FT STRAND 253..255
FT /evidence="ECO:0007829|PDB:4S2A"
FT HELIX 256..264
FT /evidence="ECO:0007829|PDB:3EPO"
FT STRAND 271..273
FT /evidence="ECO:0007829|PDB:3EPO"
FT HELIX 275..282
FT /evidence="ECO:0007829|PDB:3EPO"
FT TURN 283..285
FT /evidence="ECO:0007829|PDB:3EPO"
FT HELIX 287..289
FT /evidence="ECO:0007829|PDB:3EPO"
FT HELIX 292..305
FT /evidence="ECO:0007829|PDB:3EPO"
FT STRAND 309..312
FT /evidence="ECO:0007829|PDB:3EPO"
FT HELIX 318..324
FT /evidence="ECO:0007829|PDB:3EPO"
FT STRAND 327..329
FT /evidence="ECO:0007829|PDB:3EPO"
FT HELIX 334..346
FT /evidence="ECO:0007829|PDB:3EPO"
FT HELIX 351..354
FT /evidence="ECO:0007829|PDB:3EPO"
FT HELIX 356..363
FT /evidence="ECO:0007829|PDB:3EPO"
FT TURN 364..367
FT /evidence="ECO:0007829|PDB:3EPO"
FT STRAND 369..372
FT /evidence="ECO:0007829|PDB:3EPO"
FT HELIX 381..383
FT /evidence="ECO:0007829|PDB:3EPO"
FT HELIX 387..405
FT /evidence="ECO:0007829|PDB:3EPO"
FT STRAND 410..413
FT /evidence="ECO:0007829|PDB:3EPO"
FT HELIX 420..422
FT /evidence="ECO:0007829|PDB:3EPO"
FT HELIX 423..433
FT /evidence="ECO:0007829|PDB:3EPO"
FT TURN 434..436
FT /evidence="ECO:0007829|PDB:3EPO"
FT STRAND 439..442
FT /evidence="ECO:0007829|PDB:3EPO"
FT HELIX 454..468
FT /evidence="ECO:0007829|PDB:3EPO"
FT STRAND 472..474
FT /evidence="ECO:0007829|PDB:3EPO"
FT TURN 478..482
FT /evidence="ECO:0007829|PDB:3EPO"
FT HELIX 487..508
FT /evidence="ECO:0007829|PDB:3EPO"
FT HELIX 513..525
FT /evidence="ECO:0007829|PDB:3EPO"
FT HELIX 529..534
FT /evidence="ECO:0007829|PDB:3EPO"
FT STRAND 535..538
FT /evidence="ECO:0007829|PDB:4S2A"
FT HELIX 539..545
FT /evidence="ECO:0007829|PDB:3EPO"
FT STRAND 548..550
FT /evidence="ECO:0007829|PDB:4S2A"
FT STRAND 557..559
FT /evidence="ECO:0007829|PDB:4S2A"
FT HELIX 560..563
FT /evidence="ECO:0007829|PDB:4S2A"
FT HELIX 568..576
FT /evidence="ECO:0007829|PDB:4S2A"
FT TURN 580..583
FT /evidence="ECO:0007829|PDB:4S2A"
FT HELIX 590..602
FT /evidence="ECO:0007829|PDB:4S2A"
FT STRAND 607..610
FT /evidence="ECO:0007829|PDB:4S2A"
SQ SEQUENCE 612 AA; 67968 MW; 59FB0AFB55668816 CRC64;
MNIQSTIKAV AETISTGPIP GSRKVYQAGE LFPELRVPFR EVAVHPSANE PPVTIYDPSG
PYSDPAIQID IEKGLPRTRE ALVVARGDVE EVADPRQVKP EDNGFAQGKH LAPEFPDTGR
KIYRAKPGKL VTQLEYARAG IITAEMEYVA IRENLRREQD RPCVRDGEDF GASIPDFVTP
EFVRQEIARG RAIIPANINH GELEPMAIGR NFLVKINANI GNSAVLSTVA DEVDKLVWAT
RWGADTVMDL STGRNIHNIR DWIIRNSSVP IGTVPIYQAL EKVNGVAEDL NWEVFRDTLI
EQCEQGVDYF TIHAGVRLPF IPMTAKRVTG IVSRGGSIMA KWCLAHHKEN FLYERFDEIC
EIMRAYDVSF SLGDGLRPGS TADANDEAQF SELRTLGELT KVAWKHGVQV MIEGPGHVAM
HKIKANMDEQ LKHCHEAPFY TLGPLTTDIA PGYDHITSAI GAAMIGWFGT AMLCYVTPKE
HLGLPDRDDV KTGVITYKLA AHAADLAKGH PGAAMWDDAI SRARFEFRWE DQFNLGLDPE
TARKFHDETL PKEAHKTAHF CSMCGPKFCS MKISQEVRDF AAGKAPNSAE LGMAEMSEKF
REQGSEIYLK TE
