ACNA_MYCTU
ID ACNA_MYCTU Reviewed; 943 AA.
AC O53166; F2GES4; I6XY12; Q7D8D8;
DT 29-APR-2015, integrated into UniProtKB/Swiss-Prot.
DT 01-JUN-1998, sequence version 1.
DT 03-AUG-2022, entry version 152.
DE RecName: Full=Aconitate hydratase A {ECO:0000303|PubMed:17384188};
DE Short=ACN {ECO:0000303|PubMed:17384188};
DE Short=Aconitase {ECO:0000303|PubMed:17384188};
DE EC=4.2.1.3 {ECO:0000269|PubMed:17384188};
DE AltName: Full=(2R,3S)-2-methylisocitrate dehydratase {ECO:0000250|UniProtKB:Q8ZP52};
DE AltName: Full=(2S,3R)-3-hydroxybutane-1,2,3-tricarboxylate dehydratase {ECO:0000250|UniProtKB:Q8ZP52};
DE AltName: Full=Iron-responsive protein-like {ECO:0000303|PubMed:17384188};
DE Short=IRP-like {ECO:0000303|PubMed:17384188};
DE AltName: Full=Probable 2-methyl-cis-aconitate hydratase {ECO:0000250|UniProtKB:Q8ZP52};
DE EC=4.2.1.99 {ECO:0000250|UniProtKB:Q8ZP52};
DE AltName: Full=RNA-binding protein {ECO:0000303|PubMed:17384188};
GN Name=acn; OrderedLocusNames=Rv1475c, RVBD_1475c; ORFNames=P425_01532;
OS Mycobacterium tuberculosis (strain ATCC 25618 / H37Rv).
OC Bacteria; Actinobacteria; Corynebacteriales; Mycobacteriaceae;
OC Mycobacterium; Mycobacterium tuberculosis complex.
OX NCBI_TaxID=83332;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=ATCC 25618 / H37Rv, and H37Rv;
RX PubMed=9634230; DOI=10.1038/31159;
RA Cole S.T., Brosch R., Parkhill J., Garnier T., Churcher C.M., Harris D.E.,
RA Gordon S.V., Eiglmeier K., Gas S., Barry C.E. III, Tekaia F., Badcock K.,
RA Basham D., Brown D., Chillingworth T., Connor R., Davies R.M., Devlin K.,
RA Feltwell T., Gentles S., Hamlin N., Holroyd S., Hornsby T., Jagels K.,
RA Krogh A., McLean J., Moule S., Murphy L.D., Oliver S., Osborne J.,
RA Quail M.A., Rajandream M.A., Rogers J., Rutter S., Seeger K., Skelton S.,
RA Squares S., Squares R., Sulston J.E., Taylor K., Whitehead S.,
RA Barrell B.G.;
RT "Deciphering the biology of Mycobacterium tuberculosis from the complete
RT genome sequence.";
RL Nature 393:537-544(1998).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=ATCC 25618 / H37Rv;
RG The Broad Institute Genome Sequencing Platform;
RA Galagan J., Kreiswirth B., Dobos K., Fortune S., Fitzgerald M., Young S.K.,
RA Zeng Q., Gargeya S., Abouelleil A., Alvarado L., Berlin A.M., Chapman S.B.,
RA Gainer-Dewar J., Goldberg J., Gnerre S., Griggs A., Gujja S., Hansen M.,
RA Howarth C., Imamovic A., Larimer J., McCowan C., Murphy C., Pearson M.,
RA Poon T., Priest M., Roberts A., Saif S., Shea T., Sykes S., Wortman J.,
RA Nusbaum C., Birren B.;
RT "The genome sequence of Mycobacterium tuberculosis H37Rv.";
RL Submitted (NOV-2013) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=H37Rv;
RG The Broad Institute Genomics Platform;
RG The Broad Institute Genome Sequencing Center for Infectious Disease;
RA Earl A.M., Kreiswirth B., Gomez J., Victor T., Desjardins C., Abeel T.,
RA Young S., Zeng Q., Gargeya S., Abouelleil A., Alvarado L., Chapman S.B.,
RA Gainer-Dewar J., Goldberg J., Griggs A., Gujja S., Hansen M., Howarth C.,
RA Imamovic A., Larimer J., Murphy C., Naylor J., Pearson M., Poon T.W.,
RA Priest M., Roberts A., Saif S., Shea T., Sykes S., Wortman J., Nusbaum C.,
RA Birren B.;
RT "The genome sequence of Mycobacterium tuberculosis H37Rv.";
RL Submitted (APR-2014) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP FUNCTION, CATALYTIC ACTIVITY, BIOPHYSICOCHEMICAL PROPERTIES, AND SUBUNIT.
RX PubMed=17384188; DOI=10.1128/jb.00026-07;
RA Banerjee S., Nandyala A.K., Raviprasad P., Ahmed N., Hasnain S.E.;
RT "Iron-dependent RNA-binding activity of Mycobacterium tuberculosis
RT aconitase.";
RL J. Bacteriol. 189:4046-4052(2007).
RN [5]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC STRAIN=ATCC 25618 / H37Rv;
RX PubMed=21969609; DOI=10.1074/mcp.m111.011627;
RA Kelkar D.S., Kumar D., Kumar P., Balakrishnan L., Muthusamy B., Yadav A.K.,
RA Shrivastava P., Marimuthu A., Anand S., Sundaram H., Kingsbury R.,
RA Harsha H.C., Nair B., Prasad T.S., Chauhan D.S., Katoch K., Katoch V.M.,
RA Kumar P., Chaerkady R., Ramachandran S., Dash D., Pandey A.;
RT "Proteogenomic analysis of Mycobacterium tuberculosis by high resolution
RT mass spectrometry.";
RL Mol. Cell. Proteomics 10:M111.011627-M111.011627(2011).
RN [6]
RP INDUCTION.
RX PubMed=28237036; DOI=10.1016/j.tube.2017.01.003;
RA Balakrishnan K., Mohareer K., Banerjee S.;
RT "Mycobacterium tuberculosis Rv1474c is a TetR-like transcriptional
RT repressor that regulates aconitase, an essential enzyme and RNA-binding
RT protein, in an iron-responsive manner.";
RL Tuberculosis 103:71-82(2017).
CC -!- FUNCTION: Involved in the catabolism of short chain fatty acids (SCFA)
CC via the tricarboxylic acid (TCA)(acetyl degradation route) and probably
CC via the 2-methylcitrate cycle I (propionate degradation route).
CC Catalyzes the reversible isomerization of citrate to isocitrate via
CC cis-aconitate. The apo form of AcnA functions as a RNA-binding
CC regulatory protein which binds to selected IRE-like sequences present
CC within the UTRs (untranslated regions) of 3' trxC and 5' IdeR mRNA
CC (PubMed:17384188). Could catalyze the hydration of 2-methyl-cis-
CC aconitate to yield (2R,3S)-2-methylisocitrate (By similarity).
CC {ECO:0000250|UniProtKB:Q8ZP52, ECO:0000269|PubMed:17384188}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=citrate = D-threo-isocitrate; Xref=Rhea:RHEA:10336,
CC ChEBI:CHEBI:15562, ChEBI:CHEBI:16947; EC=4.2.1.3;
CC Evidence={ECO:0000269|PubMed:17384188};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=(2S,3R)-3-hydroxybutane-1,2,3-tricarboxylate = 2-methyl-cis-
CC aconitate + H2O; Xref=Rhea:RHEA:17941, ChEBI:CHEBI:15377,
CC ChEBI:CHEBI:57429, ChEBI:CHEBI:57872; EC=4.2.1.99;
CC Evidence={ECO:0000250|UniProtKB:Q8ZP52};
CC -!- COFACTOR:
CC Name=[4Fe-4S] cluster; Xref=ChEBI:CHEBI:49883;
CC Evidence={ECO:0000250|UniProtKB:P09339};
CC Note=Binds 1 [4Fe-4S] cluster per subunit.
CC {ECO:0000250|UniProtKB:P09339};
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=0.56 mM for isocitrate {ECO:0000269|PubMed:17384188};
CC Vmax=33.3 umol/min/mg enzyme with isocitrate as substrate
CC {ECO:0000269|PubMed:17384188};
CC pH dependence:
CC Optimum pH is 8. It retains a high specific activity over a broad pH
CC range. {ECO:0000269|PubMed:17384188};
CC -!- PATHWAY: Carbohydrate metabolism; tricarboxylic acid cycle; isocitrate
CC from oxaloacetate: step 2/2. {ECO:0000305|PubMed:17384188}.
CC -!- PATHWAY: Organic acid metabolism; propanoate degradation.
CC {ECO:0000305|PubMed:17384188}.
CC -!- SUBUNIT: Monomer. {ECO:0000269|PubMed:17384188}.
CC -!- INDUCTION: Transcriptionally regulated by Rv1474c.
CC {ECO:0000269|PubMed:28237036}.
CC -!- SIMILARITY: Belongs to the aconitase/IPM isomerase family.
CC {ECO:0000305}.
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DR EMBL; CP003248; AFN49388.1; -; Genomic_DNA.
DR EMBL; AL123456; CCP44235.1; -; Genomic_DNA.
DR EMBL; JLDD01000018; KBJ34833.1; -; Genomic_DNA.
DR RefSeq; NP_215991.1; NC_000962.3.
DR RefSeq; WP_003898889.1; NZ_NVQJ01000004.1.
DR AlphaFoldDB; O53166; -.
DR SMR; O53166; -.
DR STRING; 83332.Rv1475c; -.
DR PaxDb; O53166; -.
DR PRIDE; O53166; -.
DR DNASU; 886545; -.
DR GeneID; 886545; -.
DR KEGG; mtu:Rv1475c; -.
DR KEGG; mtv:RVBD_1475c; -.
DR PATRIC; fig|83332.111.peg.1642; -.
DR TubercuList; Rv1475c; -.
DR eggNOG; COG1048; Bacteria.
DR OMA; NGGIMQY; -.
DR PhylomeDB; O53166; -.
DR BioCyc; MetaCyc:G185E-5659-MON; -.
DR UniPathway; UPA00223; UER00718.
DR UniPathway; UPA00946; -.
DR Proteomes; UP000001584; Chromosome.
DR GO; GO:0005829; C:cytosol; HDA:MTBBASE.
DR GO; GO:0005576; C:extracellular region; HDA:MTBBASE.
DR GO; GO:0009274; C:peptidoglycan-based cell wall; HDA:MTBBASE.
DR GO; GO:0005886; C:plasma membrane; HDA:MTBBASE.
DR GO; GO:0047456; F:2-methylisocitrate dehydratase activity; ISS:UniProtKB.
DR GO; GO:0051539; F:4 iron, 4 sulfur cluster binding; ISS:UniProtKB.
DR GO; GO:0003994; F:aconitate hydratase activity; IDA:MTBBASE.
DR GO; GO:0047780; F:citrate dehydratase activity; IEA:UniProtKB-EC.
DR GO; GO:0030350; F:iron-responsive element binding; IDA:MTBBASE.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0003730; F:mRNA 3'-UTR binding; IDA:UniProtKB.
DR GO; GO:0003729; F:mRNA binding; IDA:UniProtKB.
DR GO; GO:0006101; P:citrate metabolic process; IBA:GO_Central.
DR GO; GO:0019679; P:propionate metabolic process, methylcitrate cycle; TAS:UniProtKB.
DR GO; GO:0010039; P:response to iron ion; IEP:MTBBASE.
DR GO; GO:0006099; P:tricarboxylic acid cycle; IBA:GO_Central.
DR CDD; cd01580; AcnA_IRP_Swivel; 1.
DR Gene3D; 3.20.19.10; -; 1.
DR Gene3D; 3.30.499.10; -; 2.
DR InterPro; IPR044137; AcnA_IRP_Swivel.
DR InterPro; IPR015931; Acnase/IPM_dHydase_lsu_aba_1/3.
DR InterPro; IPR001030; Acoase/IPM_deHydtase_lsu_aba.
DR InterPro; IPR015928; Aconitase/3IPM_dehydase_swvl.
DR InterPro; IPR006249; Aconitase/IRP2.
DR InterPro; IPR018136; Aconitase_4Fe-4S_BS.
DR InterPro; IPR036008; Aconitase_4Fe-4S_dom.
DR InterPro; IPR000573; AconitaseA/IPMdHydase_ssu_swvl.
DR PANTHER; PTHR11670; PTHR11670; 1.
DR Pfam; PF00330; Aconitase; 1.
DR Pfam; PF00694; Aconitase_C; 1.
DR PRINTS; PR00415; ACONITASE.
DR SUPFAM; SSF53732; SSF53732; 1.
DR PROSITE; PS00450; ACONITASE_1; 1.
DR PROSITE; PS01244; ACONITASE_2; 1.
PE 1: Evidence at protein level;
KW Iron; Iron-sulfur; Lyase; Metal-binding; Reference proteome; RNA-binding;
KW Tricarboxylic acid cycle.
FT CHAIN 1..943
FT /note="Aconitate hydratase A"
FT /id="PRO_0000432979"
FT BINDING 479
FT /ligand="[4Fe-4S] cluster"
FT /ligand_id="ChEBI:CHEBI:49883"
FT /evidence="ECO:0000250|UniProtKB:P36683"
FT BINDING 545
FT /ligand="[4Fe-4S] cluster"
FT /ligand_id="ChEBI:CHEBI:49883"
FT /evidence="ECO:0000250|UniProtKB:P36683"
FT BINDING 548
FT /ligand="[4Fe-4S] cluster"
FT /ligand_id="ChEBI:CHEBI:49883"
FT /evidence="ECO:0000250|UniProtKB:P36683"
SQ SEQUENCE 943 AA; 102449 MW; 2403292221124D1E CRC64;
MTSKSVNSFG AHDTLKVGEK SYQIYRLDAV PNTAKLPYSL KVLAENLLRN EDGSNITKDH
IEAIANWDPK AEPSIEIQYT PARVVMQDFT GVPCIVDLAT MREAIADLGG NPDKVNPLAP
ADLVIDHSVI ADLFGRADAF ERNVEIEYQR NGERYQFLRW GQGAFDDFKV VPPGTGIVHQ
VNIEYLASVV MTRDGVAYPD TCVGTDSHTT MVNGLGVLGW GVGGIEAEAA MLGQPVSMLI
PRVVGFRLTG EIQPGVTATD VVLTVTEMLR QHGVVGKFVE FYGEGVAEVP LANRATLGNM
SPEFGSTAAI FPIDEETIKY LRFTGRTPEQ VALVEAYAKA QGMWHDPKHE PEFSEYLELN
LSDVVPSIAG PKRPQDRIAL AQAKSTFREQ IYHYVGNGSP DSPHDPHSKL DEVVEETFPA
SDPGQLTFAN DDVATDETVH SAAAHADGRV SNPVRVKSDE LGEFVLDHGA VVIAAITSCT
NTSNPEVMLG AALLARNAVE KGLTSKPWVK TTIAPGSQVV NDYYDRSGLW PYLEKLGFYL
VGYGCTTCIG NSGPLPEEIS KAVNDNDLSV TAVLSGNRNF EGRINPDVKM NYLASPPLVI
AYALAGTMDF DFQTQPLGQD KDGKNVFLRD IWPSQQDVSD TIAAAINQEM FTRNYADVFK
GDDRWRNLPT PSGNTFEWDP NSTYVRKPPY FEGMTAKPEP VGNISGARVL ALLGDSVTTD
HISPAGAIKP GTPAARYLDE HGVDRKDYNS FGSRRGNHEV MIRGTFANIR LRNQLLDDVS
GGYTRDFTQP GGPQAFIYDA AQNYAAQHIP LVVFGGKEYG SGSSRDWAAK GTLLLGVRAV
IAESFERIHR SNLIGMGVIP LQFPEGKSAS SLGLDGTEVF DITGIDVLND GKTPKTVCVQ
ATKGDGATIE FDAVVRIDTP GEADYYRNGG ILQYVLRNIL KSG
