PRPB_SALTY
ID PRPB_SALTY Reviewed; 295 AA.
AC Q56062;
DT 01-NOV-1997, integrated into UniProtKB/Swiss-Prot.
DT 23-JAN-2007, sequence version 3.
DT 03-AUG-2022, entry version 133.
DE RecName: Full=2-methylisocitrate lyase {ECO:0000303|PubMed:10482501};
DE Short=2-MIC {ECO:0000303|PubMed:12897003};
DE Short=MICL {ECO:0000303|PubMed:12897003};
DE EC=4.1.3.30 {ECO:0000269|PubMed:11294638, ECO:0000269|PubMed:12897003};
DE AltName: Full=(2R,3S)-2-methylisocitrate lyase {ECO:0000255|HAMAP-Rule:MF_01939};
GN Name=prpB {ECO:0000303|PubMed:10482501}; OrderedLocusNames=STM0368;
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 [GENOMIC DNA].
RC STRAIN=LT2 / SGSC1412 / ATCC 700720;
RX PubMed=9006051; DOI=10.1128/jb.179.3.928-940.1997;
RA Horswill A.R., Escalante-Semerena J.C.;
RT "Propionate catabolism in Salmonella typhimurium LT2: two divergently
RT transcribed units comprise the prp locus at 8.5 centisomes, prpR encodes a
RT member of the sigma-54 family of activators, and the prpBCDE genes
RT constitute an operon.";
RL J. Bacteriol. 179:928-940(1997).
RN [2]
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 [3]
RP FUNCTION, AND DISRUPTION PHENOTYPE.
RX PubMed=10482501; DOI=10.1128/jb.181.18.5615-5623.1999;
RA Horswill A.R., Escalante-Semerena J.C.;
RT "Salmonella typhimurium LT2 catabolizes propionate via the 2-methylcitric
RT acid cycle.";
RL J. Bacteriol. 181:5615-5623(1999).
RN [4]
RP FUNCTION, AND CATALYTIC ACTIVITY.
RX PubMed=11294638; DOI=10.1021/bi015503b;
RA Horswill A.R., Escalante-Semerena J.C.;
RT "In vitro conversion of propionate to pyruvate by Salmonella enterica
RT enzymes: 2-methylcitrate dehydratase (PrpD) and aconitase enzymes catalyze
RT the conversion of 2-methylcitrate to 2-methylisocitrate.";
RL Biochemistry 40:4703-4713(2001).
RN [5]
RP FUNCTION, CATALYTIC ACTIVITY, BIOPHYSICOCHEMICAL PROPERTIES, MUTAGENESIS OF
RP ASP-58; LYS-121; ARG-122; CYS-123 AND HIS-125, COFACTOR, AND SUBUNIT.
RC STRAIN=LT2 / SGSC1412 / ATCC 700720;
RX PubMed=12897003; DOI=10.1128/jb.185.16.4837-4843.2003;
RA Grimek T.L., Holden H., Rayment I., Escalante-Semerena J.C.;
RT "Residues C123 and D58 of the 2-methylisocitrate lyase (PrpB) enzyme of
RT Salmonella enterica are essential for catalysis.";
RL J. Bacteriol. 185:4837-4843(2003).
RN [6]
RP X-RAY CRYSTALLOGRAPHY (2.1 ANGSTROMS) IN COMPLEX WITH SUBSTRATE AND
RP MAGNESIUM, COFACTOR, AND SUBUNIT.
RX PubMed=14575713; DOI=10.1016/j.bbrc.2003.09.193;
RA Simanshu D.K., Satheshkumar P.S., Savithri H.S., Murthy M.R.;
RT "Crystal structure of Salmonella typhimurium 2-methylisocitrate lyase
RT (PrpB) and its complex with pyruvate and Mg(2+).";
RL Biochem. Biophys. Res. Commun. 311:193-201(2003).
CC -!- FUNCTION: Involved in the catabolism of short chain fatty acids (SCFA)
CC via the 2-methylcitrate cycle I (propionate degradation route).
CC Catalyzes the thermodynamically favored C-C bond cleavage of (2R,3S)-2-
CC methylisocitrate to yield pyruvate and succinate via an alpha-carboxy-
CC carbanion intermediate. {ECO:0000255|HAMAP-Rule:MF_01939,
CC ECO:0000269|PubMed:10482501, ECO:0000269|PubMed:11294638,
CC ECO:0000269|PubMed:12897003}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=(2S,3R)-3-hydroxybutane-1,2,3-tricarboxylate = pyruvate +
CC succinate; Xref=Rhea:RHEA:16809, ChEBI:CHEBI:15361,
CC ChEBI:CHEBI:30031, ChEBI:CHEBI:57429; EC=4.1.3.30;
CC Evidence={ECO:0000255|HAMAP-Rule:MF_01939,
CC ECO:0000269|PubMed:11294638, ECO:0000269|PubMed:12897003};
CC -!- COFACTOR:
CC Name=Mg(2+); Xref=ChEBI:CHEBI:18420;
CC Evidence={ECO:0000255|HAMAP-Rule:MF_01939,
CC ECO:0000269|PubMed:12897003, ECO:0000269|PubMed:14575713};
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=18 uM for 2-methylisocitrate {ECO:0000269|PubMed:12897003};
CC Note=kcat is 74 sec(-1) for 2-methylisocitrate lyase with 2-
CC methylisocitrate as substrate. {ECO:0000269|PubMed:12897003};
CC pH dependence:
CC Optimum pH is 7.5. {ECO:0000269|PubMed:12897003};
CC Temperature dependence:
CC Optimum temperature is 50 degrees Celsius.
CC {ECO:0000269|PubMed:12897003};
CC -!- PATHWAY: Organic acid metabolism; propanoate degradation.
CC {ECO:0000255|HAMAP-Rule:MF_01939, ECO:0000305|PubMed:9006051}.
CC -!- SUBUNIT: Homotetramer; dimer of dimers. {ECO:0000255|HAMAP-
CC Rule:MF_01939, ECO:0000269|PubMed:12897003,
CC ECO:0000269|PubMed:14575713}.
CC -!- DISRUPTION PHENOTYPE: Cells lacking this gene are unable to accumulate
CC 2-methylcitrate and 2-methyl-cis-aconitate.
CC {ECO:0000269|PubMed:10482501}.
CC -!- MISCELLANEOUS: In vitro, dithiothreitol (DTT) or reduced glutathione
CC (GSH) are required for optimal activity. {ECO:0000269|PubMed:12897003}.
CC -!- SIMILARITY: Belongs to the isocitrate lyase/PEP mutase superfamily.
CC Methylisocitrate lyase family. {ECO:0000255|HAMAP-Rule:MF_01939}.
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DR EMBL; U51879; AAC44814.1; -; Genomic_DNA.
DR EMBL; AE006468; AAL19322.1; -; Genomic_DNA.
DR RefSeq; NP_459363.1; NC_003197.2.
DR RefSeq; WP_000052224.1; NC_003197.2.
DR PDB; 1O5Q; X-ray; 2.30 A; A/B/C/D=2-295.
DR PDB; 1UJQ; X-ray; 2.10 A; A/B/C/D=2-295.
DR PDBsum; 1O5Q; -.
DR PDBsum; 1UJQ; -.
DR AlphaFoldDB; Q56062; -.
DR SMR; Q56062; -.
DR STRING; 99287.STM0368; -.
DR PaxDb; Q56062; -.
DR PRIDE; Q56062; -.
DR EnsemblBacteria; AAL19322; AAL19322; STM0368.
DR GeneID; 1251887; -.
DR KEGG; stm:STM0368; -.
DR PATRIC; fig|99287.12.peg.390; -.
DR HOGENOM; CLU_027389_3_2_6; -.
DR OMA; QTELWNK; -.
DR PhylomeDB; Q56062; -.
DR BioCyc; MetaCyc:MON-66; -.
DR BioCyc; SENT99287:STM0368-MON; -.
DR UniPathway; UPA00946; -.
DR EvolutionaryTrace; Q56062; -.
DR Proteomes; UP000001014; Chromosome.
DR GO; GO:0000287; F:magnesium ion binding; IDA:UniProtKB.
DR GO; GO:0046421; F:methylisocitrate lyase activity; IDA:UniProtKB.
DR GO; GO:0019629; P:propionate catabolic process, 2-methylcitrate cycle; IDA:UniProtKB.
DR CDD; cd00377; ICL_PEPM; 1.
DR Gene3D; 3.20.20.60; -; 1.
DR HAMAP; MF_01939; PrpB; 1.
DR InterPro; IPR039556; ICL/PEPM.
DR InterPro; IPR018523; Isocitrate_lyase_ph_CS.
DR InterPro; IPR012695; PrpB.
DR InterPro; IPR015813; Pyrv/PenolPyrv_Kinase-like_dom.
DR InterPro; IPR040442; Pyrv_Kinase-like_dom_sf.
DR SUPFAM; SSF51621; SSF51621; 1.
DR TIGRFAMs; TIGR02317; prpB; 1.
DR PROSITE; PS00161; ISOCITRATE_LYASE; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Lyase; Magnesium; Metal-binding; Reference proteome.
FT INIT_MET 1
FT /note="Removed"
FT /evidence="ECO:0000305"
FT CHAIN 2..295
FT /note="2-methylisocitrate lyase"
FT /id="PRO_0000068816"
FT BINDING 45..47
FT /ligand="substrate"
FT /evidence="ECO:0000269|PubMed:14575713"
FT BINDING 85
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /evidence="ECO:0000269|PubMed:14575713"
FT BINDING 87
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_01939"
FT BINDING 123..124
FT /ligand="substrate"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_01939"
FT BINDING 158
FT /ligand="substrate"
FT /evidence="ECO:0000269|PubMed:14575713"
FT BINDING 188
FT /ligand="substrate"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_01939"
FT BINDING 210..212
FT /ligand="substrate"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_01939"
FT BINDING 241
FT /ligand="substrate"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_01939"
FT BINDING 270
FT /ligand="substrate"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_01939"
FT MUTAGEN 58
FT /note="D->A: Inactive. Retains the same oligomeric state of
FT the wild-type."
FT /evidence="ECO:0000269|PubMed:12897003"
FT MUTAGEN 121
FT /note="K->A: 1000-fold decrease in the catalytic
FT efficiency. Retains the same oligomeric state of the wild-
FT type."
FT /evidence="ECO:0000269|PubMed:12897003"
FT MUTAGEN 122
FT /note="R->K: 2-fold decrease in the catalytic efficiency.
FT Retains the same oligomeric state of the wild-type."
FT /evidence="ECO:0000269|PubMed:12897003"
FT MUTAGEN 123
FT /note="C->A: Inactive. Retains the same oligomeric state of
FT the wild-type."
FT /evidence="ECO:0000269|PubMed:12897003"
FT MUTAGEN 125
FT /note="H->A: 750-fold decrease in the catalytic efficiency.
FT Retains the same oligomeric state of the wild-type."
FT /evidence="ECO:0000269|PubMed:12897003"
FT HELIX 6..16
FT /evidence="ECO:0007829|PDB:1UJQ"
FT STRAND 17..24
FT /evidence="ECO:0007829|PDB:1UJQ"
FT HELIX 28..37
FT /evidence="ECO:0007829|PDB:1UJQ"
FT STRAND 40..44
FT /evidence="ECO:0007829|PDB:1UJQ"
FT HELIX 46..51
FT /evidence="ECO:0007829|PDB:1UJQ"
FT STRAND 58..60
FT /evidence="ECO:0007829|PDB:1UJQ"
FT HELIX 64..77
FT /evidence="ECO:0007829|PDB:1UJQ"
FT STRAND 82..85
FT /evidence="ECO:0007829|PDB:1UJQ"
FT STRAND 90..93
FT /evidence="ECO:0007829|PDB:1UJQ"
FT HELIX 94..106
FT /evidence="ECO:0007829|PDB:1UJQ"
FT STRAND 110..115
FT /evidence="ECO:0007829|PDB:1UJQ"
FT HELIX 134..147
FT /evidence="ECO:0007829|PDB:1UJQ"
FT STRAND 153..159
FT /evidence="ECO:0007829|PDB:1UJQ"
FT HELIX 161..165
FT /evidence="ECO:0007829|PDB:1UJQ"
FT HELIX 167..179
FT /evidence="ECO:0007829|PDB:1UJQ"
FT STRAND 183..187
FT /evidence="ECO:0007829|PDB:1UJQ"
FT HELIX 193..203
FT /evidence="ECO:0007829|PDB:1UJQ"
FT STRAND 207..210
FT /evidence="ECO:0007829|PDB:1UJQ"
FT STRAND 213..217
FT /evidence="ECO:0007829|PDB:1UJQ"
FT HELIX 222..227
FT /evidence="ECO:0007829|PDB:1UJQ"
FT STRAND 232..237
FT /evidence="ECO:0007829|PDB:1UJQ"
FT HELIX 238..257
FT /evidence="ECO:0007829|PDB:1UJQ"
FT STRAND 258..260
FT /evidence="ECO:0007829|PDB:1O5Q"
FT HELIX 261..266
FT /evidence="ECO:0007829|PDB:1UJQ"
FT HELIX 270..276
FT /evidence="ECO:0007829|PDB:1UJQ"
FT HELIX 279..285
FT /evidence="ECO:0007829|PDB:1UJQ"
SQ SEQUENCE 295 AA; 32000 MW; 08AD38D071B98F1D CRC64;
MSLHSPGQAF RAALAKENPL QIVGAINANH ALLAQRAGYQ AIYLSGGGVA AGSLGLPDLG
ISTLDDVLTD IRRITDVCPL PLLVDADIGF GSSAFNVART VKSIAKAGAA ALHIEDQVGA
KRCGHRPNKA IVSKEEMVDR IRAAVDARTD PNFVIMARTD ALAVEGLEAA LDRAQAYVDA
GADMLFPEAI TELSMYRRFA DVAQVPILAN ITEFGATPLF TTDELRSAHV AMALYPLSAF
RAMNRAAEKV YTVLRQEGTQ KNVIDIMQTR NELYESINYY QFEEKLDALY RNKKS
