FGE_THECD
ID FGE_THECD Reviewed; 303 AA.
AC D1A7C3;
DT 20-JUN-2018, integrated into UniProtKB/Swiss-Prot.
DT 19-JAN-2010, sequence version 1.
DT 03-AUG-2022, entry version 62.
DE RecName: Full=Formylglycine-generating enzyme {ECO:0000303|PubMed:26403223, ECO:0000303|PubMed:27862795};
DE Short=FGE {ECO:0000303|PubMed:26403223, ECO:0000303|PubMed:27862795};
DE EC=1.8.3.7 {ECO:0000269|PubMed:26403223, ECO:0000269|PubMed:27862795};
GN OrderedLocusNames=Tcur_4811 {ECO:0000312|EMBL:ACZ00329.1};
OS Thermomonospora curvata (strain ATCC 19995 / DSM 43183 / JCM 3096 / KCTC
OS 9072 / NBRC 15933 / NCIMB 10081 / Henssen B9).
OC Bacteria; Actinobacteria; Streptosporangiales; Thermomonosporaceae;
OC Thermomonospora.
OX NCBI_TaxID=471852;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=ATCC 19995 / DSM 43183 / JCM 3096 / KCTC 9072 / NBRC 15933 / NCIMB
RC 10081 / Henssen B9;
RX PubMed=21475583; DOI=10.4056/sigs.1453580;
RA Chertkov O., Sikorski J., Nolan M., Lapidus A., Lucas S., Del Rio T.G.,
RA Tice H., Cheng J.F., Goodwin L., Pitluck S., Liolios K., Ivanova N.,
RA Mavromatis K., Mikhailova N., Ovchinnikova G., Pati A., Chen A.,
RA Palaniappan K., Djao O.D., Land M., Hauser L., Chang Y.J., Jeffries C.D.,
RA Brettin T., Han C., Detter J.C., Rohde M., Goeker M., Woyke T., Bristow J.,
RA Eisen J.A., Markowitz V., Hugenholtz P., Klenk H.P., Kyrpides N.C.;
RT "Complete genome sequence of Thermomonospora curvata type strain (B9).";
RL Stand. Genomic Sci. 1:13-22(2011).
RN [2]
RP FUNCTION, CATALYTIC ACTIVITY, PATHWAY, COFACTOR, BIOPHYSICOCHEMICAL
RP PROPERTIES, AND MUTAGENESIS OF CYS-187; CYS-231; CYS-284 AND CYS-298.
RX PubMed=26403223; DOI=10.1002/cbic.201500322;
RA Knop M., Engi P., Lemnaru R., Seebeck F.P.;
RT "In vitro reconstitution of formylglycine-generating enzymes requires
RT copper(I).";
RL ChemBioChem 16:2147-2150(2015).
RN [3]
RP FUNCTION, CATALYTIC ACTIVITY, COFACTOR, BIOPHYSICOCHEMICAL PROPERTIES, AND
RP MUTAGENESIS OF CYS-187; CYS-231; CYS-269; CYS-274; CYS-284 AND CYS-298.
RX PubMed=27862795; DOI=10.1002/cbic.201600359;
RA Knop M., Dang T.Q., Jeschke G., Seebeck F.P.;
RT "Copper is a cofactor of the formylglycine-generating enzyme.";
RL ChemBioChem 18:161-165(2017).
RN [4] {ECO:0007744|PDB:5NXL, ECO:0007744|PDB:5NYY}
RP X-RAY CRYSTALLOGRAPHY (1.28 ANGSTROMS) OF 20-303 IN COMPLEX WITH CALCIUM
RP AND SILVER, COPPER-BINDING SITES, AND REACTION MECHANISM.
RX PubMed=28544744; DOI=10.1002/anie.201702901;
RA Meury M., Knop M., Seebeck F.P.;
RT "Structural basis for copper-oxygen mediated C-H bond activation by the
RT formylglycine-generating enzyme.";
RL Angew. Chem. Int. Ed. Engl. 56:8115-8119(2017).
CC -!- FUNCTION: Oxidase that catalyzes the conversion of cysteine to 3-
CC oxoalanine on target proteins. 3-oxoalanine modification, which is also
CC named formylglycine (fGly), occurs in the maturation of arylsulfatases
CC and some alkaline phosphatases that use the hydrated form of 3-
CC oxoalanine as a catalytic nucleophile. {ECO:0000269|PubMed:26403223,
CC ECO:0000269|PubMed:27862795}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=2 a thiol + L-cysteinyl-[sulfatase] + O2 = 3-oxo-L-alanyl-
CC [sulfatase] + an organic disulfide + H(+) + H2O + hydrogen sulfide;
CC Xref=Rhea:RHEA:51152, Rhea:RHEA-COMP:12900, Rhea:RHEA-COMP:12901,
CC ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:15379,
CC ChEBI:CHEBI:29256, ChEBI:CHEBI:29919, ChEBI:CHEBI:29950,
CC ChEBI:CHEBI:35489, ChEBI:CHEBI:85621; EC=1.8.3.7;
CC Evidence={ECO:0000269|PubMed:26403223, ECO:0000269|PubMed:27862795};
CC -!- COFACTOR:
CC Name=Cu(+); Xref=ChEBI:CHEBI:49552;
CC Evidence={ECO:0000269|PubMed:26403223, ECO:0000269|PubMed:27862795,
CC ECO:0000269|PubMed:28544744};
CC Note=The catalytic copper is required to activate oxygen and catalyze
CC oxidative C-H activation. {ECO:0000269|PubMed:28544744};
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=580 uM for [sulfatase]-L-cysteine (in presence of Cu(+))
CC {ECO:0000269|PubMed:27862795};
CC Note=kcat is 1.6 min(-1) in presence of Cu(+).
CC {ECO:0000269|PubMed:26403223, ECO:0000269|PubMed:27862795};
CC -!- PATHWAY: Protein modification; sulfatase oxidation.
CC {ECO:0000269|PubMed:26403223, ECO:0000269|PubMed:27862795}.
CC -!- SIMILARITY: Belongs to the sulfatase-modifying factor family.
CC {ECO:0000305}.
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DR EMBL; CP001738; ACZ00329.1; -; Genomic_DNA.
DR PDB; 5NXL; X-ray; 1.66 A; A=20-303.
DR PDB; 5NYY; X-ray; 1.28 A; A=20-303.
DR PDB; 6S07; X-ray; 1.04 A; A=1-302.
DR PDB; 6XTL; X-ray; 1.80 A; A=1-302.
DR PDB; 6XTM; X-ray; 1.25 A; A=1-302.
DR PDB; 6XTN; X-ray; 1.40 A; A=1-302.
DR PDB; 6XTO; X-ray; 1.40 A; A=1-302.
DR PDB; 6XTP; X-ray; 1.80 A; A=1-302.
DR PDB; 6XTQ; X-ray; 1.40 A; A=1-302.
DR PDB; 6XTR; X-ray; 1.20 A; A=1-302.
DR PDB; 6XTS; X-ray; 1.20 A; A=1-302.
DR PDBsum; 5NXL; -.
DR PDBsum; 5NYY; -.
DR PDBsum; 6S07; -.
DR PDBsum; 6XTL; -.
DR PDBsum; 6XTM; -.
DR PDBsum; 6XTN; -.
DR PDBsum; 6XTO; -.
DR PDBsum; 6XTP; -.
DR PDBsum; 6XTQ; -.
DR PDBsum; 6XTR; -.
DR PDBsum; 6XTS; -.
DR AlphaFoldDB; D1A7C3; -.
DR SMR; D1A7C3; -.
DR STRING; 471852.Tcur_4811; -.
DR EnsemblBacteria; ACZ00329; ACZ00329; Tcur_4811.
DR KEGG; tcu:Tcur_4811; -.
DR eggNOG; COG1262; Bacteria.
DR HOGENOM; CLU_012431_4_2_11; -.
DR OMA; YEWTADC; -.
DR UniPathway; UPA00910; -.
DR Proteomes; UP000001918; Chromosome.
DR GO; GO:1903136; F:cuprous ion binding; IDA:UniProtKB.
DR GO; GO:0120147; F:Formylglycine-generating oxidase activity; IDA:UniProtKB.
DR GO; GO:0043687; P:post-translational protein modification; IDA:UniProtKB.
DR GO; GO:0018158; P:protein oxidation; IDA:UniProtKB.
DR Gene3D; 3.90.1580.10; -; 1.
DR InterPro; IPR016187; CTDL_fold.
DR InterPro; IPR005532; SUMF_dom.
DR InterPro; IPR042095; SUMF_sf.
DR Pfam; PF03781; FGE-sulfatase; 1.
DR SUPFAM; SSF56436; SSF56436; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Calcium; Copper; Metal-binding; Oxidoreductase;
KW Reference proteome.
FT CHAIN 1..303
FT /note="Formylglycine-generating enzyme"
FT /id="PRO_0000444618"
FT BINDING 188
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="1"
FT /evidence="ECO:0000269|PubMed:28544744,
FT ECO:0007744|PDB:5NXL, ECO:0007744|PDB:5NYY"
FT BINDING 189
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="1"
FT /evidence="ECO:0000269|PubMed:28544744,
FT ECO:0007744|PDB:5NXL, ECO:0007744|PDB:5NYY"
FT BINDING 202
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="1"
FT /evidence="ECO:0000269|PubMed:28544744,
FT ECO:0007744|PDB:5NXL, ECO:0007744|PDB:5NYY"
FT BINDING 204
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="1"
FT /evidence="ECO:0000269|PubMed:28544744,
FT ECO:0007744|PDB:5NXL, ECO:0007744|PDB:5NYY"
FT BINDING 222
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="2"
FT /evidence="ECO:0000269|PubMed:28544744,
FT ECO:0007744|PDB:5NXL, ECO:0007744|PDB:5NYY"
FT BINDING 223
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="2"
FT /evidence="ECO:0000269|PubMed:28544744,
FT ECO:0007744|PDB:5NXL, ECO:0007744|PDB:5NYY"
FT BINDING 225
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="2"
FT /evidence="ECO:0000269|PubMed:28544744,
FT ECO:0007744|PDB:5NXL, ECO:0007744|PDB:5NYY"
FT BINDING 227
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="2"
FT /evidence="ECO:0000269|PubMed:28544744,
FT ECO:0007744|PDB:5NXL, ECO:0007744|PDB:5NYY"
FT BINDING 269
FT /ligand="Cu(+)"
FT /ligand_id="ChEBI:CHEBI:49552"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000269|PubMed:27862795,
FT ECO:0000269|PubMed:28544744, ECO:0007744|PDB:5NXL,
FT ECO:0007744|PDB:5NYY"
FT BINDING 274
FT /ligand="Cu(+)"
FT /ligand_id="ChEBI:CHEBI:49552"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000269|PubMed:27862795,
FT ECO:0000269|PubMed:28544744, ECO:0007744|PDB:5NXL,
FT ECO:0007744|PDB:5NYY"
FT MUTAGEN 187
FT /note="C->A: In 4C; increased formylglycine-generating
FT enzyme activity; when associated with A-231; A-284 and A-
FT 298."
FT /evidence="ECO:0000269|PubMed:26403223,
FT ECO:0000269|PubMed:27862795"
FT MUTAGEN 231
FT /note="C->A: In 4C; increased formylglycine-generating
FT enzyme activity; when associated with A-187; A-284 and A-
FT 298."
FT /evidence="ECO:0000269|PubMed:26403223,
FT ECO:0000269|PubMed:27862795"
FT MUTAGEN 269
FT /note="C->S: Abolished formylglycine-generating enzyme
FT activity and ability to bind Cu(+)."
FT /evidence="ECO:0000269|PubMed:27862795"
FT MUTAGEN 274
FT /note="C->S: Abolished formylglycine-generating enzyme
FT activity and ability to bind Cu(+)."
FT /evidence="ECO:0000269|PubMed:27862795"
FT MUTAGEN 284
FT /note="C->A: In 4C; increased formylglycine-generating
FT enzyme activity; when associated with A-187; A-231 and A-
FT 298."
FT /evidence="ECO:0000269|PubMed:26403223,
FT ECO:0000269|PubMed:27862795"
FT MUTAGEN 298
FT /note="C->A: In 4C; increased formylglycine-generating
FT enzyme activity; when associated with A-187; A-231 and A-
FT 284."
FT /evidence="ECO:0000269|PubMed:26403223,
FT ECO:0000269|PubMed:27862795"
FT HELIX 13..17
FT /evidence="ECO:0007829|PDB:6S07"
FT STRAND 20..23
FT /evidence="ECO:0007829|PDB:6S07"
FT STRAND 25..31
FT /evidence="ECO:0007829|PDB:6S07"
FT HELIX 39..41
FT /evidence="ECO:0007829|PDB:6S07"
FT STRAND 47..51
FT /evidence="ECO:0007829|PDB:6S07"
FT STRAND 54..59
FT /evidence="ECO:0007829|PDB:6S07"
FT HELIX 63..73
FT /evidence="ECO:0007829|PDB:6S07"
FT HELIX 78..82
FT /evidence="ECO:0007829|PDB:6S07"
FT STRAND 84..88
FT /evidence="ECO:0007829|PDB:6S07"
FT HELIX 89..91
FT /evidence="ECO:0007829|PDB:6S07"
FT STRAND 109..113
FT /evidence="ECO:0007829|PDB:6S07"
FT HELIX 140..149
FT /evidence="ECO:0007829|PDB:6S07"
FT HELIX 157..165
FT /evidence="ECO:0007829|PDB:6S07"
FT HELIX 181..183
FT /evidence="ECO:0007829|PDB:6S07"
FT TURN 194..196
FT /evidence="ECO:0007829|PDB:6S07"
FT STRAND 223..234
FT /evidence="ECO:0007829|PDB:6S07"
FT HELIX 239..241
FT /evidence="ECO:0007829|PDB:6S07"
FT HELIX 245..248
FT /evidence="ECO:0007829|PDB:6S07"
FT STRAND 258..264
FT /evidence="ECO:0007829|PDB:6S07"
FT TURN 271..274
FT /evidence="ECO:0007829|PDB:6S07"
FT STRAND 283..285
FT /evidence="ECO:0007829|PDB:6S07"
SQ SEQUENCE 303 AA; 33276 MW; FFAF53CCC62F82DA CRC64;
MPSFDFDIPR RSPQEIAKGM VAIPGGTFRM GGEDPDAFPE DGEGPVRTVR LSPFLIDRYA
VSNRQFAAFV KATGYVTDAE RYGWSFVFHA HVAPGTPVMD AVVPEAPWWV AVPGAYWKAP
EGPGSSITDR PNHPVVHVSW NDAVAYATWA GKRLPTEAEW EMAARGGLDQ ARYPWGNELT
PRGRHRCNIW QGTFPVHDTG EDGYTGTAPV NAFAPNGYGL YNVAGNVWEW CADWWSADWH
ATESPATRID PRGPETGTAR VTKGGSFLCH ESYCNRYRVA ARTCNTPDSS AAHTGFRCAA
DPL
