ACEA2_MYCTO
ID ACEA2_MYCTO Reviewed; 766 AA.
AC Q8VJU4;
DT 01-APR-2015, integrated into UniProtKB/Swiss-Prot.
DT 13-SEP-2004, sequence version 2.
DT 03-AUG-2022, entry version 104.
DE RecName: Full=Isocitrate lyase 2 {ECO:0000303|PubMed:10572116};
DE Short=ICL2 {ECO:0000303|PubMed:10572116};
DE EC=4.1.3.1 {ECO:0000269|PubMed:10572116, ECO:0000269|PubMed:16879647};
DE AltName: Full=Isocitrase {ECO:0000303|PubMed:10572116};
DE AltName: Full=Isocitratase {ECO:0000303|PubMed:10572116};
GN Name=icl2; Synonyms=aceA-2; OrderedLocusNames=MT1966;
OS Mycobacterium tuberculosis (strain CDC 1551 / Oshkosh).
OC Bacteria; Actinobacteria; Corynebacteriales; Mycobacteriaceae;
OC Mycobacterium; Mycobacterium tuberculosis complex.
OX NCBI_TaxID=83331;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=CDC 1551 / Oshkosh;
RX PubMed=12218036; DOI=10.1128/jb.184.19.5479-5490.2002;
RA Fleischmann R.D., Alland D., Eisen J.A., Carpenter L., White O.,
RA Peterson J.D., DeBoy R.T., Dodson R.J., Gwinn M.L., Haft D.H., Hickey E.K.,
RA Kolonay J.F., Nelson W.C., Umayam L.A., Ermolaeva M.D., Salzberg S.L.,
RA Delcher A., Utterback T.R., Weidman J.F., Khouri H.M., Gill J., Mikula A.,
RA Bishai W., Jacobs W.R. Jr., Venter J.C., Fraser C.M.;
RT "Whole-genome comparison of Mycobacterium tuberculosis clinical and
RT laboratory strains.";
RL J. Bacteriol. 184:5479-5490(2002).
RN [2]
RP FUNCTION, CATALYTIC ACTIVITY, BIOPHYSICOCHEMICAL PROPERTIES, ACTIVITY
RP REGULATION, AND INDUCTION.
RC STRAIN=CDC 1551 / Oshkosh;
RX PubMed=10572116; DOI=10.1128/jb.181.23.7161-7167.1999;
RA Honer Zu Bentrup K., Miczak A., Swenson D.L., Russell D.G.;
RT "Characterization of activity and expression of isocitrate lyase in
RT Mycobacterium avium and Mycobacterium tuberculosis.";
RL J. Bacteriol. 181:7161-7167(1999).
RN [3]
RP FUNCTION, DISRUPTION PHENOTYPE, AND ACTIVITY REGULATION.
RX PubMed=15895072; DOI=10.1038/nm1252;
RA Munoz-Elias E.J., McKinney J.D.;
RT "Mycobacterium tuberculosis isocitrate lyases 1 and 2 are jointly required
RT for in vivo growth and virulence.";
RL Nat. Med. 11:638-644(2005).
RN [4]
RP FUNCTION, CATALYTIC ACTIVITY, AND BIOPHYSICOCHEMICAL PROPERTIES.
RX PubMed=16879647; DOI=10.1111/j.1365-2958.2006.05297.x;
RA Gould T.A., van de Langemheen H., Munoz-Elias E.J., McKinney J.D.,
RA Sacchettini J.C.;
RT "Dual role of isocitrate lyase 1 in the glyoxylate and methylcitrate cycles
RT in Mycobacterium tuberculosis.";
RL Mol. Microbiol. 61:940-947(2006).
CC -!- FUNCTION: Involved in the persistence and virulence of M.tuberculosis.
CC Catalyzes the reversible formation of succinate and glyoxylate from
CC isocitrate, a key step of the glyoxylate cycle, which operates as an
CC anaplerotic route for replenishing the tricarboxylic acid cycle during
CC growth on fatty acid substrates. {ECO:0000269|PubMed:10572116,
CC ECO:0000269|PubMed:15895072, ECO:0000269|PubMed:16879647}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=D-threo-isocitrate = glyoxylate + succinate;
CC Xref=Rhea:RHEA:13245, ChEBI:CHEBI:15562, ChEBI:CHEBI:30031,
CC ChEBI:CHEBI:36655; EC=4.1.3.1; Evidence={ECO:0000269|PubMed:10572116,
CC ECO:0000269|PubMed:16879647};
CC -!- COFACTOR:
CC Name=Mg(2+); Xref=ChEBI:CHEBI:18420;
CC Evidence={ECO:0000250|UniProtKB:P9WKK7};
CC -!- ACTIVITY REGULATION: Inhibited by itaconate, itaconic anhydride,
CC bromopyruvate and 3-nitropropionate (3-NP), when M.tuberculosis grows
CC on fatty acids, but not on glucose. Succinate at 5 mM inhibits the
CC activity to approximately 50%. {ECO:0000269|PubMed:10572116,
CC ECO:0000269|PubMed:15895072}.
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=1.2 mM for threo-DL-isocitrate (ICA) (at pH 6.8)
CC {ECO:0000269|PubMed:16879647};
CC KM=1.3 mM for threo-D-isocitrate (at pH 7.5 and 37 degrees Celsius)
CC {ECO:0000269|PubMed:10572116};
CC Vmax=0.41 umol/min/mg enzyme with threo-D-isocitrate as substrate (at
CC pH 7.5 and 37 degrees Celsius) {ECO:0000269|PubMed:10572116};
CC Note=kcat is 1.38 sec(-1) for isocitrate lyase activity with threo-
CC DL-isocitrate as substrate (at pH 6). {ECO:0000269|PubMed:16879647};
CC -!- PATHWAY: Carbohydrate metabolism; glyoxylate cycle; (S)-malate from
CC isocitrate: step 1/2. {ECO:0000305|PubMed:16879647}.
CC -!- INDUCTION: Induced by palmitate, acetate and glucose. Repressed by
CC succinate. {ECO:0000269|PubMed:10572116}.
CC -!- DISRUPTION PHENOTYPE: Deletion of icl2 has a little effect on
CC replication in media containing glycerol, glucose, short-chain fatty
CC acids or long-chain fatty acids. Cells lacking icl2 have no discernible
CC impact on the kinetics of M.tuberculosis growth and persistence.
CC However deletion of both icl1 and icl2 eliminates growth on fatty acids
CC but has little effect on use of carbohydrates. Cells lacking both genes
CC are incapable of growth in mice and are rapidly eliminated from the
CC lungs and spleen. {ECO:0000269|PubMed:15895072}.
CC -!- SIMILARITY: Belongs to the isocitrate lyase/PEP mutase superfamily.
CC Isocitrate lyase family. {ECO:0000305}.
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DR EMBL; AE000516; AAK46238.2; -; Genomic_DNA.
DR RefSeq; WP_003409584.1; NZ_KK341227.1.
DR AlphaFoldDB; Q8VJU4; -.
DR SMR; Q8VJU4; -.
DR EnsemblBacteria; AAK46238; AAK46238; MT1966.
DR KEGG; mtc:MT1966; -.
DR HOGENOM; CLU_019214_1_0_11; -.
DR UniPathway; UPA00703; UER00719.
DR Proteomes; UP000001020; Chromosome.
DR GO; GO:0004451; F:isocitrate lyase activity; IEA:UniProtKB-EC.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0006097; P:glyoxylate cycle; IEA:UniProtKB-UniPathway.
DR GO; GO:0006099; P:tricarboxylic acid cycle; IEA:UniProtKB-KW.
DR CDD; cd00377; ICL_PEPM; 1.
DR Gene3D; 3.20.20.60; -; 1.
DR InterPro; IPR039556; ICL/PEPM.
DR InterPro; IPR006254; Isocitrate_lyase.
DR InterPro; IPR018523; Isocitrate_lyase_ph_CS.
DR InterPro; IPR015813; Pyrv/PenolPyrv_Kinase-like_dom.
DR InterPro; IPR040442; Pyrv_Kinase-like_dom_sf.
DR PANTHER; PTHR21631; PTHR21631; 1.
DR Pfam; PF00463; ICL; 2.
DR SUPFAM; SSF51621; SSF51621; 1.
DR PROSITE; PS00161; ISOCITRATE_LYASE; 1.
PE 1: Evidence at protein level;
KW Glyoxylate bypass; Lyase; Magnesium; Metal-binding;
KW Tricarboxylic acid cycle.
FT CHAIN 1..766
FT /note="Isocitrate lyase 2"
FT /id="PRO_0000432568"
FT ACT_SITE 215
FT /note="Proton acceptor"
FT /evidence="ECO:0000250|UniProtKB:P9WKK7"
FT BINDING 106..108
FT /ligand="substrate"
FT /evidence="ECO:0000250|UniProtKB:P9WKK7"
FT BINDING 177
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /evidence="ECO:0000250|UniProtKB:P9WKK7"
FT BINDING 216..217
FT /ligand="substrate"
FT /evidence="ECO:0000250|UniProtKB:P9WKK7"
FT BINDING 252
FT /ligand="substrate"
FT /evidence="ECO:0000250|UniProtKB:P9WKK7"
FT BINDING 487..491
FT /ligand="substrate"
FT /evidence="ECO:0000250|UniProtKB:P9WKK7"
FT BINDING 522
FT /ligand="substrate"
FT /evidence="ECO:0000250|UniProtKB:P9WKK7"
SQ SEQUENCE 766 AA; 85320 MW; 9F6B78CFAF23B6AA CRC64;
MAIAETDTEV HTPFEQDFEK DVAATQRYFD SSRFAGIIRL YTARQVVEQR GTIPVDHIVA
REAAGAFYER LRELFAARKS ITTFGPYSPG QAVSMKRMGI EAIYLGGWAT SAKGSSTEDP
GPDLASYPLS QVPDDAAVLV RALLTADRNQ HYLRLQMSER QRAATPAYDF RPFIIADADT
GHGGDPHVRN LIRRFVEVGV PGYHIEDQRP GTKKCGHQGG KVLVPSDEQI KRLNAARFQL
DIMRVPGIIV ARTDAEAANL IDSRADERDQ PFLLGATKLD VPSYKSCFLA MVRRFYELGV
KELNGHLLYA LGDSEYAAAG GWLERQGIFG LVSDAVNAWR EDGQQSIDGI FDQVESRFVA
AWEDDAGLMT YGEAVADVLE FGQSEGEPIG MAPEEWRAFA ARASLHAARA KAKELGADPP
WDCELAKTPE GYYQIRGGIP YAIAKSLAAA PFADILWMET KTADLADARQ FAEAIHAEFP
DQMLAYNLSP SFNWDTTGMT DEEMRRFPEE LGKMGFVFNF ITYGGHQIDG VAAEEFATAL
RQDGMLALAR LQRKMRLVES PYRTPQTLVG GPRSDAALAA SSGRTATTKA MGKGSTQHQH
LVQTEVPRKL LEEWLAMWSG HYQLKDKLRV QLRPQRAGSE VLELGIHGES DDKLANVIFQ
PIQDRRGRTI LLVRDQNTFG AELRQKRLMT LIHLWLVHRF KAQAVHYVTP TDDNLYQTSK
MKSHGIFTEV NQEVGEIIVA EVNHPRIAEL LTPDRVALRK LITKEA
