CEAS_STRCL
ID CEAS_STRCL Reviewed; 573 AA.
AC Q9LCV9;
DT 29-OCT-2014, integrated into UniProtKB/Swiss-Prot.
DT 01-OCT-2000, sequence version 1.
DT 03-AUG-2022, entry version 94.
DE RecName: Full=N(2)-(2-carboxyethyl)arginine synthase {ECO:0000303|PubMed:14623876};
DE Short=CEA synthetase {ECO:0000303|PubMed:14623876};
DE Short=CEAS {ECO:0000303|PubMed:14623876};
DE EC=2.5.1.66 {ECO:0000269|PubMed:18052280, ECO:0000269|Ref.5};
GN Name=ceaS {ECO:0000303|PubMed:10681345};
OS Streptomyces clavuligerus.
OC Bacteria; Actinobacteria; Streptomycetales; Streptomycetaceae;
OC Streptomyces.
OX NCBI_TaxID=1901;
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RC STRAIN=NRRL3585;
RX PubMed=8088547; DOI=10.1016/0378-1119(94)90036-1;
RA Aidoo K.A., Wong A., Alexander D.C., Rittammer R.A.R., Jensen S.E.;
RT "Cloning, sequencing and disruption of a gene from Streptomyces
RT clavuligerus involved in clavulanic acid biosynthesis.";
RL Gene 147:41-46(1994).
RN [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RC STRAIN=NRRL3585;
RX PubMed=8892828; DOI=10.1128/jb.178.21.6266-6274.1996;
RA Paradkar A.S., Aidoo K.A., Wong A., Jensen S.E.;
RT "Molecular analysis of a beta-lactam resistance gene encoded within the
RT cephamycin gene cluster of Streptomyces clavuligerus.";
RL J. Bacteriol. 178:6266-6274(1996).
RN [3]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RC STRAIN=NRRL3585;
RX PubMed=9515708; DOI=10.1046/j.1365-2958.1998.00731.x;
RA Paradkar A.S., Aidoo K.A., Jensen S.E.;
RT "A pathway-specific transcriptional activator regulates late steps of
RT clavulanic acid biosynthesis in Streptomyces clavuligerus.";
RL Mol. Microbiol. 27:831-843(1998).
RN [4]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RC STRAIN=NRRL3585;
RX PubMed=10681345; DOI=10.1128/aac.44.3.720-726.2000;
RA Jensen S.E., Elder K.J., Aidoo K.A., Paradkar A.S.;
RT "Enzymes catalyzing the early steps of clavulanic acid biosynthesis are
RT encoded by two sets of paralogous genes in Streptomyces clavuligerus.";
RL Antimicrob. Agents Chemother. 44:720-726(2000).
RN [5]
RP FUNCTION, CATALYTIC ACTIVITY, AND COFACTOR.
RA Khaleeli N., Li R., Townsend C.A.;
RT "Origin of the beta-lactam carbons in clavulanic acid from an unusual
RT thiamine pyrophosphate-mediated reaction.";
RL (er) J. Am. Chem. Soc. 121:9223-9224(1999).
RN [6]
RP FUNCTION, CATALYTIC ACTIVITY, COFACTOR, AND REACTION MECHANISM.
RX PubMed=18052280; DOI=10.1021/ja076704r;
RA Merski M., Townsend C.A.;
RT "Observation of an acryloyl-thiamin diphosphate adduct in the first step of
RT clavulanic acid biosynthesis.";
RL J. Am. Chem. Soc. 129:15750-15751(2007).
RN [7]
RP X-RAY CRYSTALLOGRAPHY (2.35 ANGSTROMS) IN COMPLEX WITH THIAMINE
RP PYROPHOSPHATE AND MAGNESIUM IONS, COFACTOR, SUBUNIT, AND MASS SPECTROMETRY.
RX PubMed=14623876; DOI=10.1074/jbc.m310803200;
RA Caines M.E., Elkins J.M., Hewitson K.S., Schofield C.J.;
RT "Crystal structure and mechanistic implications of N2-(2-
RT carboxyethyl)arginine synthase, the first enzyme in the clavulanic acid
RT biosynthesis pathway.";
RL J. Biol. Chem. 279:5685-5692(2004).
RN [8]
RP X-RAY CRYSTALLOGRAPHY (2.00 ANGSTROMS) IN COMPLEX WITH SUBSTRATE ANALOGS;
RP THIAMINE PYROPHOSPHATE AND MAGNESIUM IONS, COFACTOR, SUBUNIT, AND REACTION
RP MECHANISM.
RX PubMed=19477162; DOI=10.1016/j.bbrc.2009.05.095;
RA Caines M.E., Sorensen J.L., Schofield C.J.;
RT "Structural and mechanistic studies on N(2)-(2-carboxyethyl)arginine
RT synthase.";
RL Biochem. Biophys. Res. Commun. 385:512-517(2009).
CC -!- FUNCTION: Involved in the biosynthesis of the beta-lactamase inhibitor,
CC clavulanic acid. Catalyzes the thiamine diphosphate (ThDP) dependent
CC condensation of D-glyceraldehyde-3-phosphate (D-G3P) with L-arginine to
CC yield the beta-amino acid, N2-(2-carboxyethyl)arginine (CEA) via a
CC beta-elimination resulting in the formation of an enol which undergoes
CC a second elimination to generate the alpha,beta-unsaturated acryloyl-
CC ThDP. {ECO:0000269|PubMed:18052280, ECO:0000269|Ref.5}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=D-glyceraldehyde 3-phosphate + L-arginine = H(+) + N(2)-(2-
CC carboxyethyl)-L-arginine + phosphate; Xref=Rhea:RHEA:10556,
CC ChEBI:CHEBI:15378, ChEBI:CHEBI:32682, ChEBI:CHEBI:43474,
CC ChEBI:CHEBI:57304, ChEBI:CHEBI:59776; EC=2.5.1.66;
CC Evidence={ECO:0000269|PubMed:18052280, ECO:0000269|Ref.5};
CC -!- COFACTOR:
CC Name=Mg(2+); Xref=ChEBI:CHEBI:18420;
CC Evidence={ECO:0000269|PubMed:14623876, ECO:0000269|PubMed:19477162,
CC ECO:0000269|Ref.5};
CC Note=Binds 1 Mg(2+) ion per subunit. {ECO:0000269|PubMed:14623876,
CC ECO:0000269|PubMed:19477162, ECO:0000269|Ref.5};
CC -!- COFACTOR:
CC Name=thiamine diphosphate; Xref=ChEBI:CHEBI:58937;
CC Evidence={ECO:0000269|PubMed:14623876, ECO:0000269|PubMed:18052280,
CC ECO:0000269|PubMed:19477162, ECO:0000269|Ref.5};
CC Note=Binds 1 thiamine pyrophosphate per subunit.
CC {ECO:0000269|PubMed:14623876, ECO:0000269|PubMed:18052280,
CC ECO:0000269|PubMed:19477162, ECO:0000269|Ref.5};
CC -!- SUBUNIT: Homotetramer; dimer of dimers. {ECO:0000269|PubMed:14623876,
CC ECO:0000269|PubMed:19477162}.
CC -!- MASS SPECTROMETRY: Mass=60776; Method=Electrospray;
CC Evidence={ECO:0000269|PubMed:14623876};
CC -!- SIMILARITY: Belongs to the TPP enzyme family. {ECO:0000305}.
CC ---------------------------------------------------------------------------
CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms
CC Distributed under the Creative Commons Attribution (CC BY 4.0) License
CC ---------------------------------------------------------------------------
DR EMBL; U87786; AAF86619.1; -; Genomic_DNA.
DR RefSeq; WP_003952509.1; NZ_CP032052.1.
DR PDB; 1UPA; X-ray; 2.35 A; A/B/C/D=1-573.
DR PDB; 1UPB; X-ray; 2.35 A; A/B/C/D=1-573.
DR PDB; 1UPC; X-ray; 2.45 A; A/B/C/D/E/F=1-573.
DR PDB; 2IHT; X-ray; 2.00 A; A/B/C/D=1-573.
DR PDB; 2IHU; X-ray; 2.05 A; A/B/C/D=1-573.
DR PDB; 2IHV; X-ray; 2.30 A; A/B/C/D=1-573.
DR PDBsum; 1UPA; -.
DR PDBsum; 1UPB; -.
DR PDBsum; 1UPC; -.
DR PDBsum; 2IHT; -.
DR PDBsum; 2IHU; -.
DR PDBsum; 2IHV; -.
DR AlphaFoldDB; Q9LCV9; -.
DR SMR; Q9LCV9; -.
DR STRING; 443255.SCLAV_4197; -.
DR DrugBank; DB01987; Cocarboxylase.
DR PRIDE; Q9LCV9; -.
DR GeneID; 61469723; -.
DR BioCyc; MetaCyc:MON-13478; -.
DR EvolutionaryTrace; Q9LCV9; -.
DR GO; GO:0000287; F:magnesium ion binding; IDA:UniProtKB.
DR GO; GO:0033848; F:N2-(2-carboxyethyl)arginine synthase activity; IDA:UniProtKB.
DR GO; GO:0030976; F:thiamine pyrophosphate binding; IDA:UniProtKB.
DR InterPro; IPR029035; DHS-like_NAD/FAD-binding_dom.
DR InterPro; IPR029061; THDP-binding.
DR InterPro; IPR012000; Thiamin_PyroP_enz_cen_dom.
DR InterPro; IPR012001; Thiamin_PyroP_enz_TPP-bd_dom.
DR InterPro; IPR000399; TPP-bd_CS.
DR InterPro; IPR045229; TPP_enz.
DR InterPro; IPR011766; TPP_enzyme-bd_C.
DR PANTHER; PTHR18968; PTHR18968; 1.
DR Pfam; PF02775; TPP_enzyme_C; 1.
DR Pfam; PF00205; TPP_enzyme_M; 1.
DR Pfam; PF02776; TPP_enzyme_N; 1.
DR SUPFAM; SSF52467; SSF52467; 1.
DR SUPFAM; SSF52518; SSF52518; 2.
DR PROSITE; PS00187; TPP_ENZYMES; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Magnesium; Metal-binding; Thiamine pyrophosphate;
KW Transferase.
FT INIT_MET 1
FT /note="Removed"
FT /evidence="ECO:0000269|PubMed:14623876"
FT CHAIN 2..573
FT /note="N(2)-(2-carboxyethyl)arginine synthase"
FT /id="PRO_0000430817"
FT BINDING 271
FT /ligand="substrate"
FT /evidence="ECO:0000269|PubMed:19477162"
FT BINDING 301
FT /ligand="substrate"
FT /evidence="ECO:0000269|PubMed:19477162"
FT BINDING 410..413
FT /ligand="thiamine diphosphate"
FT /ligand_id="ChEBI:CHEBI:58937"
FT /evidence="ECO:0000269|PubMed:14623876,
FT ECO:0000269|PubMed:19477162"
FT BINDING 414..415
FT /ligand="substrate"
FT /evidence="ECO:0000269|PubMed:19477162"
FT BINDING 436..438
FT /ligand="thiamine diphosphate"
FT /ligand_id="ChEBI:CHEBI:58937"
FT /evidence="ECO:0000269|PubMed:14623876,
FT ECO:0000269|PubMed:19477162"
FT BINDING 463
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /evidence="ECO:0000269|PubMed:14623876,
FT ECO:0000269|PubMed:19477162"
FT BINDING 464..465
FT /ligand="thiamine diphosphate"
FT /ligand_id="ChEBI:CHEBI:58937"
FT /evidence="ECO:0000269|PubMed:14623876,
FT ECO:0000269|PubMed:19477162"
FT BINDING 490..495
FT /ligand="thiamine diphosphate"
FT /ligand_id="ChEBI:CHEBI:58937"
FT /evidence="ECO:0000269|PubMed:14623876,
FT ECO:0000269|PubMed:19477162"
FT BINDING 490
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /evidence="ECO:0000269|PubMed:14623876,
FT ECO:0000269|PubMed:19477162"
FT BINDING 492
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /evidence="ECO:0000269|PubMed:14623876,
FT ECO:0000269|PubMed:19477162"
FT BINDING 561
FT /ligand="thiamine diphosphate"
FT /ligand_id="ChEBI:CHEBI:58937"
FT /evidence="ECO:0000269|PubMed:14623876,
FT ECO:0000269|PubMed:19477162"
FT BINDING 571
FT /ligand="substrate"
FT /evidence="ECO:0000269|PubMed:19477162"
FT HELIX 14..24
FT /evidence="ECO:0007829|PDB:2IHT"
FT STRAND 29..32
FT /evidence="ECO:0007829|PDB:2IHT"
FT HELIX 36..39
FT /evidence="ECO:0007829|PDB:2IHT"
FT STRAND 50..53
FT /evidence="ECO:0007829|PDB:2IHT"
FT HELIX 57..71
FT /evidence="ECO:0007829|PDB:2IHT"
FT STRAND 75..79
FT /evidence="ECO:0007829|PDB:2IHT"
FT HELIX 83..98
FT /evidence="ECO:0007829|PDB:2IHT"
FT STRAND 102..109
FT /evidence="ECO:0007829|PDB:2IHT"
FT HELIX 111..113
FT /evidence="ECO:0007829|PDB:2IHT"
FT TURN 116..118
FT /evidence="ECO:0007829|PDB:2IHT"
FT HELIX 125..129
FT /evidence="ECO:0007829|PDB:2IHT"
FT HELIX 130..132
FT /evidence="ECO:0007829|PDB:2IHT"
FT STRAND 133..138
FT /evidence="ECO:0007829|PDB:2IHT"
FT HELIX 142..144
FT /evidence="ECO:0007829|PDB:2IHT"
FT HELIX 145..156
FT /evidence="ECO:0007829|PDB:2IHT"
FT STRAND 158..160
FT /evidence="ECO:0007829|PDB:2IHT"
FT STRAND 164..169
FT /evidence="ECO:0007829|PDB:2IHT"
FT HELIX 170..173
FT /evidence="ECO:0007829|PDB:2IHT"
FT STRAND 181..183
FT /evidence="ECO:0007829|PDB:2IHV"
FT STRAND 195..198
FT /evidence="ECO:0007829|PDB:2IHT"
FT HELIX 202..215
FT /evidence="ECO:0007829|PDB:2IHT"
FT STRAND 217..223
FT /evidence="ECO:0007829|PDB:2IHT"
FT HELIX 225..229
FT /evidence="ECO:0007829|PDB:2IHT"
FT HELIX 233..243
FT /evidence="ECO:0007829|PDB:2IHT"
FT STRAND 247..249
FT /evidence="ECO:0007829|PDB:2IHT"
FT TURN 252..255
FT /evidence="ECO:0007829|PDB:2IHT"
FT STRAND 264..267
FT /evidence="ECO:0007829|PDB:2IHT"
FT HELIX 272..276
FT /evidence="ECO:0007829|PDB:2IHT"
FT HELIX 280..285
FT /evidence="ECO:0007829|PDB:2IHT"
FT STRAND 290..294
FT /evidence="ECO:0007829|PDB:2IHT"
FT HELIX 298..300
FT /evidence="ECO:0007829|PDB:2IHT"
FT HELIX 304..307
FT /evidence="ECO:0007829|PDB:2IHT"
FT STRAND 314..321
FT /evidence="ECO:0007829|PDB:2IHT"
FT TURN 326..328
FT /evidence="ECO:0007829|PDB:2IHT"
FT STRAND 332..337
FT /evidence="ECO:0007829|PDB:2IHT"
FT HELIX 339..349
FT /evidence="ECO:0007829|PDB:2IHT"
FT TURN 350..352
FT /evidence="ECO:0007829|PDB:2IHT"
FT HELIX 362..372
FT /evidence="ECO:0007829|PDB:2IHT"
FT STRAND 379..382
FT /evidence="ECO:0007829|PDB:2IHT"
FT HELIX 384..398
FT /evidence="ECO:0007829|PDB:2IHT"
FT STRAND 405..408
FT /evidence="ECO:0007829|PDB:2IHT"
FT HELIX 412..420
FT /evidence="ECO:0007829|PDB:2IHT"
FT STRAND 428..430
FT /evidence="ECO:0007829|PDB:2IHT"
FT STRAND 433..435
FT /evidence="ECO:0007829|PDB:2IHT"
FT HELIX 441..451
FT /evidence="ECO:0007829|PDB:2IHT"
FT STRAND 457..462
FT /evidence="ECO:0007829|PDB:2IHT"
FT HELIX 463..468
FT /evidence="ECO:0007829|PDB:2IHT"
FT HELIX 469..472
FT /evidence="ECO:0007829|PDB:2IHT"
FT HELIX 473..479
FT /evidence="ECO:0007829|PDB:2IHT"
FT STRAND 484..489
FT /evidence="ECO:0007829|PDB:2IHT"
FT HELIX 494..504
FT /evidence="ECO:0007829|PDB:2IHT"
FT HELIX 509..511
FT /evidence="ECO:0007829|PDB:2IHT"
FT HELIX 519..525
FT /evidence="ECO:0007829|PDB:2IHT"
FT STRAND 529..532
FT /evidence="ECO:0007829|PDB:2IHT"
FT HELIX 536..547
FT /evidence="ECO:0007829|PDB:2IHT"
FT STRAND 549..551
FT /evidence="ECO:0007829|PDB:2IHT"
FT STRAND 553..559
FT /evidence="ECO:0007829|PDB:2IHT"
FT HELIX 565..567
FT /evidence="ECO:0007829|PDB:2IHT"
FT HELIX 569..571
FT /evidence="ECO:0007829|PDB:2IHT"
SQ SEQUENCE 573 AA; 60907 MW; 87624F6C0281C714 CRC64;
MSRVSTAPSG KPTAAHALLS RLRDHGVGKV FGVVGREAAS ILFDEVEGID FVLTRHEFTA
GVAADVLARI TGRPQACWAT LGPGMTNLST GIATSVLDRS PVIALAAQSE SHDIFPNDTH
QCLDSVAIVA PMSKYAVELQ RPHEITDLVD SAVNAAMTEP VGPSFISLPV DLLGSSEGID
TTVPNPPANT PAKPVGVVAD GWQKAADQAA ALLAEAKHPV LVVGAAAIRS GAVPAIRALA
ERLNIPVITT YIAKGVLPVG HELNYGAVTG YMDGILNFPA LQTMFAPVDL VLTVGYDYAE
DLRPSMWQKG IEKKTVRISP TVNPIPRVYR PDVDVVTDVL AFVEHFETAT ASFGAKQRHD
IEPLRARIAE FLADPETYED GMRVHQVIDS MNTVMEEAAE PGEGTIVSDI GFFRHYGVLF
ARADQPFGFL TSAGCSSFGY GIPAAIGAQM ARPDQPTFLI AGDGGFHSNS SDLETIARLN
LPIVTVVVNN DTNGLIELYQ NIGHHRSHDP AVKFGGVDFV ALAEANGVDA TRATNREELL
AALRKGAELG RPFLIEVPVN YDFQPGGFGA LSI
