GLAH_ECOLI
ID GLAH_ECOLI Reviewed; 325 AA.
AC P76621; Q2MAC7; Q9ZAZ9;
DT 01-JUN-2001, integrated into UniProtKB/Swiss-Prot.
DT 01-JUN-2001, sequence version 2.
DT 03-AUG-2022, entry version 143.
DE RecName: Full=Glutarate 2-hydroxylase {ECO:0000303|PubMed:30498244};
DE Short=G-2-H {ECO:0000303|PubMed:30498244};
DE EC=1.14.11.64 {ECO:0000269|PubMed:30498244};
DE AltName: Full=Carbon starvation induced protein D {ECO:0000303|PubMed:9512707};
GN Name=glaH {ECO:0000303|PubMed:30498244};
GN Synonyms=csiD {ECO:0000303|PubMed:9512707},
GN gab {ECO:0000303|PubMed:11910018}, ygaT; OrderedLocusNames=b2659, JW5427;
OS Escherichia coli (strain K12).
OC Bacteria; Proteobacteria; Gammaproteobacteria; Enterobacterales;
OC Enterobacteriaceae; Escherichia.
OX NCBI_TaxID=83333;
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RC STRAIN=K12 / CS101;
RA Diab K., Metzer E., Halpern Y.S.;
RT "The involvement of the gabC locus in the control of utilization of gama-
RT aminobutyric acid in E.coli K-12.";
RL Submitted (AUG-1996) to the EMBL/GenBank/DDBJ databases.
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=K12 / MG1655 / ATCC 47076;
RX PubMed=9278503; DOI=10.1126/science.277.5331.1453;
RA Blattner F.R., Plunkett G. III, Bloch C.A., Perna N.T., Burland V.,
RA Riley M., Collado-Vides J., Glasner J.D., Rode C.K., Mayhew G.F.,
RA Gregor J., Davis N.W., Kirkpatrick H.A., Goeden M.A., Rose D.J., Mau B.,
RA Shao Y.;
RT "The complete genome sequence of Escherichia coli K-12.";
RL Science 277:1453-1462(1997).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=K12 / W3110 / ATCC 27325 / DSM 5911;
RX PubMed=16738553; DOI=10.1038/msb4100049;
RA Hayashi K., Morooka N., Yamamoto Y., Fujita K., Isono K., Choi S.,
RA Ohtsubo E., Baba T., Wanner B.L., Mori H., Horiuchi T.;
RT "Highly accurate genome sequences of Escherichia coli K-12 strains MG1655
RT and W3110.";
RL Mol. Syst. Biol. 2:E1-E5(2006).
RN [4]
RP TRANSCRIPTIONAL REGULATION, AND PROTEIN SEQUENCE OF N-TERMINUS.
RX PubMed=9512707; DOI=10.1006/jmbi.1997.1533;
RA Marschall C., Labrousse V., Kreimer M., Weichart D., Kolb A.,
RA Hengge-Aronis R.;
RT "Molecular analysis of the regulation of csiD, a carbon starvation-
RT inducible gene in Escherichia coli that is exclusively dependent on sigma s
RT and requires activation by cAMP-CRP.";
RL J. Mol. Biol. 276:339-353(1998).
RN [5]
RP INDUCTION.
RC STRAIN=K12 / MC4100 / ATCC 35695 / DSM 6574;
RX PubMed=14731280; DOI=10.1046/j.1365-2958.2003.03867.x;
RA Metzner M., Germer J., Hengge R.;
RT "Multiple stress signal integration in the regulation of the complex sigma
RT S-dependent csiD-ygaF-gabDTP operon in Escherichia coli.";
RL Mol. Microbiol. 51:799-811(2004).
RN [6]
RP X-RAY CRYSTALLOGRAPHY (2.0 ANGSTROMS) OF 15-325 IN COMPLEX WITH IRON,
RP COFACTOR, AND SUBUNIT.
RX PubMed=11910018; DOI=10.1110/ps.4570102;
RA Chance M.R., Bresnick A.R., Burley S.K., Jiang J.-S., Lima C.D., Sali A.,
RA Almo S.C., Bonanno J.B., Buglino J.A., Boulton S., Chen H., Eswar N.,
RA He G., Huang R., Ilyin V., McMahan L., Pieper U., Ray S., Vidal M.,
RA Wang L.K.;
RT "Structural genomics: a pipeline for providing structures for the
RT biologist.";
RL Protein Sci. 11:723-738(2002).
RN [7]
RP X-RAY CRYSTALLOGRAPHY (2.20 ANGSTROMS) IN COMPLEXES WITH IRON; GLUTARATE;
RP SUCCINATE AND THE INHIBITOR N-OXALYLGLYCINE, FUNCTION, CATALYTIC ACTIVITY,
RP SUBSTRATE SPECIFICITY, COFACTOR, BIOPHYSICOCHEMICAL PROPERTIES, DISRUPTION
RP PHENOTYPE, AND PATHWAY.
RC STRAIN=K12 / BW25113;
RX PubMed=30498244; DOI=10.1038/s41467-018-07563-6;
RA Knorr S., Sinn M., Galetskiy D., Williams R.M., Wang C., Mueller N.,
RA Mayans O., Schleheck D., Hartig J.S.;
RT "Widespread bacterial lysine degradation proceeding via glutarate and L-2-
RT hydroxyglutarate.";
RL Nat. Commun. 9:5071-5071(2018).
CC -!- FUNCTION: Acts as an alpha-ketoglutarate-dependent dioxygenase
CC catalyzing hydroxylation of glutarate (GA) to L-2-hydroxyglutarate
CC (L2HG) in the stationary phase of E.coli. Functions in a L-lysine
CC degradation pathway that proceeds via cadaverine, glutarate and L-2-
CC hydroxyglutarate. Other dicarboxylic acids (oxalate, malonate,
CC succinate, adipate, and pimelate) are not substrates for this enzyme.
CC {ECO:0000269|PubMed:30498244}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=2-oxoglutarate + glutarate + O2 = (S)-2-hydroxyglutarate + CO2
CC + succinate; Xref=Rhea:RHEA:13821, ChEBI:CHEBI:15379,
CC ChEBI:CHEBI:16526, ChEBI:CHEBI:16782, ChEBI:CHEBI:16810,
CC ChEBI:CHEBI:30031, ChEBI:CHEBI:30921; EC=1.14.11.64;
CC Evidence={ECO:0000269|PubMed:30498244};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:13822;
CC Evidence={ECO:0000269|PubMed:30498244};
CC -!- COFACTOR:
CC Name=Fe(2+); Xref=ChEBI:CHEBI:29033;
CC Evidence={ECO:0000269|PubMed:11910018, ECO:0000269|PubMed:30498244};
CC Note=Binds 1 Fe(2+) ion per subunit. {ECO:0000269|PubMed:11910018,
CC ECO:0000269|PubMed:30498244};
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=650 uM for glutarate {ECO:0000269|PubMed:30498244};
CC KM=100 uM for 2-oxoglutarate {ECO:0000269|PubMed:30498244};
CC -!- PATHWAY: Amino-acid degradation. {ECO:0000269|PubMed:30498244}.
CC -!- SUBUNIT: Homotetramer. {ECO:0000269|PubMed:11910018}.
CC -!- INDUCTION: Expression is induced by RpoS during carbon starvation and
CC at stationary phase. Is also regulated by cAMP-CRP and Lrp, which play
CC the roles of a nearly essential activator and of a positive modulator,
CC respectively. Repressed by CsiR. Makes part of the operon glaH-lhgD-
CC gabDTP. {ECO:0000269|PubMed:14731280, ECO:0000269|PubMed:9512707}.
CC -!- DISRUPTION PHENOTYPE: Cells lacking this gene accumulate higher levels
CC of glutarate than wild-type during carbon starvation and entry into the
CC stationary phase. {ECO:0000269|PubMed:30498244}.
CC -!- SIMILARITY: Belongs to the glutarate hydroxylase family. {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAD10865.1; Type=Erroneous initiation; Note=Extended N-terminus.; Evidence={ECO:0000305};
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DR EMBL; U68243; AAD10865.1; ALT_INIT; Genomic_DNA.
DR EMBL; U00096; AAC75706.2; -; Genomic_DNA.
DR EMBL; AP009048; BAE76779.1; -; Genomic_DNA.
DR PIR; D65045; D65045.
DR RefSeq; NP_417145.4; NC_000913.3.
DR RefSeq; WP_000993126.1; NZ_LN832404.1.
DR PDB; 1JR7; X-ray; 2.00 A; A=15-325.
DR PDB; 6GPE; X-ray; 2.20 A; A/B=1-325.
DR PDB; 6HL8; X-ray; 2.40 A; A/B=1-325.
DR PDBsum; 1JR7; -.
DR PDBsum; 6GPE; -.
DR PDBsum; 6HL8; -.
DR AlphaFoldDB; P76621; -.
DR SMR; P76621; -.
DR BioGRID; 4259208; 8.
DR STRING; 511145.b2659; -.
DR jPOST; P76621; -.
DR PaxDb; P76621; -.
DR PRIDE; P76621; -.
DR EnsemblBacteria; AAC75706; AAC75706; b2659.
DR EnsemblBacteria; BAE76779; BAE76779; BAE76779.
DR GeneID; 948076; -.
DR KEGG; ecj:JW5427; -.
DR KEGG; eco:b2659; -.
DR PATRIC; fig|1411691.4.peg.4082; -.
DR EchoBASE; EB3295; -.
DR eggNOG; ENOG502Z8GB; Bacteria.
DR HOGENOM; CLU_075277_0_0_6; -.
DR OMA; HNDGTFV; -.
DR PhylomeDB; P76621; -.
DR BioCyc; EcoCyc:G7394-MON; -.
DR BioCyc; MetaCyc:G7394-MON; -.
DR BRENDA; 1.14.11.64; 2026.
DR EvolutionaryTrace; P76621; -.
DR PRO; PR:P76621; -.
DR Proteomes; UP000000318; Chromosome.
DR Proteomes; UP000000625; Chromosome.
DR GO; GO:0032991; C:protein-containing complex; IDA:EcoCyc.
DR GO; GO:0016706; F:2-oxoglutarate-dependent dioxygenase activity; IDA:EcoCyc.
DR GO; GO:0008198; F:ferrous iron binding; IDA:UniProtKB.
DR GO; GO:0106343; F:glutarate dioxygenase activity; IEA:UniProtKB-EC.
DR GO; GO:0042802; F:identical protein binding; IDA:EcoCyc.
DR GO; GO:0005506; F:iron ion binding; IDA:EcoCyc.
DR GO; GO:0050498; F:oxidoreductase activity, acting on paired donors, with incorporation or reduction of molecular oxygen, with 2-oxoglutarate as one donor, and the other dehydrogenated; IDA:UniProtKB.
DR GO; GO:0019477; P:L-lysine catabolic process; IDA:UniProtKB.
DR GO; GO:0090549; P:response to carbon starvation; IEP:EcoCyc.
DR Gene3D; 3.60.130.10; -; 1.
DR HAMAP; MF_01083; glutarate_hydroxylase; 1.
DR InterPro; IPR015038; GlaH.
DR InterPro; IPR042098; TauD-like_sf.
DR Pfam; PF08943; CsiD; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Dioxygenase; Direct protein sequencing; Iron; Metal-binding;
KW Oxidoreductase; Reference proteome.
FT CHAIN 1..325
FT /note="Glutarate 2-hydroxylase"
FT /id="PRO_0000218177"
FT BINDING 160
FT /ligand="Fe cation"
FT /ligand_id="ChEBI:CHEBI:24875"
FT /evidence="ECO:0000269|PubMed:11910018,
FT ECO:0000269|PubMed:30498244, ECO:0000312|PDB:1JR7,
FT ECO:0000312|PDB:6GPE"
FT BINDING 162
FT /ligand="Fe cation"
FT /ligand_id="ChEBI:CHEBI:24875"
FT /evidence="ECO:0000269|PubMed:11910018,
FT ECO:0000269|PubMed:30498244, ECO:0000312|PDB:1JR7,
FT ECO:0000312|PDB:6GPE"
FT BINDING 292
FT /ligand="Fe cation"
FT /ligand_id="ChEBI:CHEBI:24875"
FT /evidence="ECO:0000269|PubMed:11910018,
FT ECO:0000269|PubMed:30498244, ECO:0000312|PDB:1JR7,
FT ECO:0000312|PDB:6GPE"
FT CONFLICT 152..153
FT /note="QP -> HA (in Ref. 1; AAD10865)"
FT /evidence="ECO:0000305"
FT CONFLICT 212..213
FT /note="MR -> IA (in Ref. 1; AAD10865)"
FT /evidence="ECO:0000305"
FT CONFLICT 310..311
FT /note="QR -> HG (in Ref. 1; AAD10865)"
FT /evidence="ECO:0000305"
FT STRAND 19..25
FT /evidence="ECO:0007829|PDB:1JR7"
FT STRAND 32..37
FT /evidence="ECO:0007829|PDB:1JR7"
FT HELIX 39..49
FT /evidence="ECO:0007829|PDB:1JR7"
FT HELIX 54..59
FT /evidence="ECO:0007829|PDB:1JR7"
FT HELIX 62..74
FT /evidence="ECO:0007829|PDB:1JR7"
FT TURN 75..77
FT /evidence="ECO:0007829|PDB:1JR7"
FT HELIX 79..88
FT /evidence="ECO:0007829|PDB:1JR7"
FT STRAND 94..99
FT /evidence="ECO:0007829|PDB:1JR7"
FT HELIX 105..107
FT /evidence="ECO:0007829|PDB:1JR7"
FT HELIX 108..122
FT /evidence="ECO:0007829|PDB:1JR7"
FT STRAND 123..125
FT /evidence="ECO:0007829|PDB:1JR7"
FT TURN 129..131
FT /evidence="ECO:0007829|PDB:1JR7"
FT STRAND 132..140
FT /evidence="ECO:0007829|PDB:1JR7"
FT STRAND 157..160
FT /evidence="ECO:0007829|PDB:1JR7"
FT STRAND 166..168
FT /evidence="ECO:0007829|PDB:1JR7"
FT STRAND 172..182
FT /evidence="ECO:0007829|PDB:1JR7"
FT STRAND 188..192
FT /evidence="ECO:0007829|PDB:1JR7"
FT HELIX 193..195
FT /evidence="ECO:0007829|PDB:1JR7"
FT HELIX 199..203
FT /evidence="ECO:0007829|PDB:1JR7"
FT HELIX 206..209
FT /evidence="ECO:0007829|PDB:1JR7"
FT STRAND 212..214
FT /evidence="ECO:0007829|PDB:1JR7"
FT STRAND 226..228
FT /evidence="ECO:0007829|PDB:1JR7"
FT STRAND 230..233
FT /evidence="ECO:0007829|PDB:1JR7"
FT STRAND 239..241
FT /evidence="ECO:0007829|PDB:1JR7"
FT TURN 245..247
FT /evidence="ECO:0007829|PDB:1JR7"
FT HELIX 253..267
FT /evidence="ECO:0007829|PDB:1JR7"
FT STRAND 273..275
FT /evidence="ECO:0007829|PDB:1JR7"
FT STRAND 282..286
FT /evidence="ECO:0007829|PDB:1JR7"
FT TURN 287..289
FT /evidence="ECO:0007829|PDB:1JR7"
FT STRAND 290..294
FT /evidence="ECO:0007829|PDB:1JR7"
FT STRAND 304..314
FT /evidence="ECO:0007829|PDB:1JR7"
SQ SEQUENCE 325 AA; 37360 MW; AF403B3029E0B7F4 CRC64;
MNALTAVQNN AVDSGQDYSG FTLTPSAQSP RLLELTFTEQ TTKQFLEQVA EWPVQALEYK
SFLRFRVAKI LDDLCANQLQ PLLLKTLLNR AEGALLINAV GVDDVKQADE MVKLATAVAH
LIGRSNFDAM SGQYYARFVV KNVDNSDSYL RQPHRVMELH NDGTYVEEIT DYVLMMKIDE
QNMQGGNSLL LHLDDWEHLD NYFRHPLARR PMRFAAPPSK NVSKDVFHPV FDVDQQGRPV
MRYIDQFVQP KDFEEGVWLS ELSDAIETSK GILSVPVPVG KFLLINNLFW LHGRDRFTPH
PDLRRELMRQ RGYFAYASNH YQTHQ
