HOA_MYCTU
ID HOA_MYCTU Reviewed; 346 AA.
AC P9WMK5; L0TFQ6; P71867; Q7D5C4;
DT 16-APR-2014, integrated into UniProtKB/Swiss-Prot.
DT 16-APR-2014, sequence version 1.
DT 03-AUG-2022, entry version 38.
DE RecName: Full=4-hydroxy-2-oxohexanoate aldolase {ECO:0000305};
DE EC=4.1.3.43 {ECO:0000269|PubMed:23614353};
DE AltName: Full=4-hydroxy-2-keto-pentanoic acid aldolase {ECO:0000255|HAMAP-Rule:MF_01656};
DE AltName: Full=4-hydroxy-2-oxopentanoate aldolase {ECO:0000255|HAMAP-Rule:MF_01656};
DE AltName: Full=4-hydroxy-2-oxovalerate aldolase {ECO:0000255|HAMAP-Rule:MF_01656};
DE Short=HOA {ECO:0000255|HAMAP-Rule:MF_01656};
DE EC=4.1.3.39 {ECO:0000255|HAMAP-Rule:MF_01656, ECO:0000269|PubMed:23614353};
GN Name=hsaF {ECO:0000303|PubMed:23614353}; OrderedLocusNames=Rv3534c;
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;
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 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 [3] {ECO:0007744|PDB:4JN6}
RP X-RAY CRYSTALLOGRAPHY (1.93 ANGSTROMS) IN COMPLEX WITH HSAG; MANGANESE AND
RP OXALATE, FUNCTION, CATALYTIC ACTIVITY, COFACTOR, ACTIVITY REGULATION,
RP BIOPHYSICOCHEMICAL PROPERTIES, SUBUNIT, AND MUTAGENESIS OF GLY-322.
RC STRAIN=H37Rv;
RX PubMed=23614353; DOI=10.1021/bi400351h;
RA Carere J., McKenna S.E., Kimber M.S., Seah S.Y.;
RT "Characterization of an aldolase-dehydrogenase complex from the cholesterol
RT degradation pathway of Mycobacterium tuberculosis.";
RL Biochemistry 52:3502-3511(2013).
CC -!- FUNCTION: Involved in cholesterol degradation. Catalyzes the retro-
CC aldol cleavage of 4-hydroxy-2-oxohexanoate (HOHA) to pyruvate and
CC propanal. Can also catalyze the cleavage of 4-hydroxy-2-oxopentanoate
CC (HOPA) to pyruvate and acetaldehyde. The aldehydes produced by this
CC reaction are directly channeled to the dehydrogenase HsaG.
CC {ECO:0000269|PubMed:23614353}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=(S)-4-hydroxy-2-oxohexanoate = propanal + pyruvate;
CC Xref=Rhea:RHEA:36003, ChEBI:CHEBI:15361, ChEBI:CHEBI:17153,
CC ChEBI:CHEBI:73142; EC=4.1.3.43;
CC Evidence={ECO:0000269|PubMed:23614353};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:36004;
CC Evidence={ECO:0000269|PubMed:23614353};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=(S)-4-hydroxy-2-oxopentanoate = acetaldehyde + pyruvate;
CC Xref=Rhea:RHEA:22624, ChEBI:CHEBI:15343, ChEBI:CHEBI:15361,
CC ChEBI:CHEBI:73143; EC=4.1.3.39; Evidence={ECO:0000255|HAMAP-
CC Rule:MF_01656, ECO:0000269|PubMed:23614353};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:22625;
CC Evidence={ECO:0000269|PubMed:23614353};
CC -!- COFACTOR:
CC Name=Mn(2+); Xref=ChEBI:CHEBI:29035;
CC Evidence={ECO:0000269|PubMed:23614353};
CC Name=Ni(2+); Xref=ChEBI:CHEBI:49786;
CC Evidence={ECO:0000269|PubMed:23614353};
CC Name=Co(2+); Xref=ChEBI:CHEBI:48828;
CC Evidence={ECO:0000269|PubMed:23614353};
CC Note=Requires a divalent metal cation. Activity is highest in the
CC presence of Mn(2+), followed by Co(2+) and Ni(2+). Mg(2+) and Ca(2+)
CC are poor metal cofactors. No activity with Cd(2+), Zn(2+) or Cu(2+).
CC {ECO:0000269|PubMed:23614353};
CC -!- ACTIVITY REGULATION: Shows aldolase activity only when expressed and
CC copurified with HsaG. This arrangement probably prevents the
CC deleterious formation and release of toxic aldehydes in the absence of
CC the partner dehydrogenase. {ECO:0000269|PubMed:23614353}.
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=4.8 uM for 4-hydroxy-2-oxohexanoate {ECO:0000269|PubMed:23614353};
CC KM=4.4 uM for 4-hydroxy-2-oxopentanoate
CC {ECO:0000269|PubMed:23614353};
CC Note=kcat is 0.38 sec(-1) with 4-hydroxy-2-oxohexanoate as substrate.
CC kcat is 0.41 sec(-1) with 4-hydroxy-2-oxopentanoate as substrate.
CC {ECO:0000269|PubMed:23614353};
CC -!- SUBUNIT: Homodimer. Forms an heterotetramer composed of two aldolase
CC (HsaF) and two dehydrogenase (HsaG) subunits.
CC {ECO:0000269|PubMed:23614353}.
CC -!- SIMILARITY: Belongs to the 4-hydroxy-2-oxovalerate aldolase family.
CC {ECO:0000255|HAMAP-Rule:MF_01656}.
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DR EMBL; AL123456; CCP46356.1; -; Genomic_DNA.
DR PIR; G70675; G70675.
DR RefSeq; NP_218051.1; NC_000962.3.
DR RefSeq; WP_003419250.1; NZ_NVQJ01000014.1.
DR PDB; 4JN6; X-ray; 1.93 A; A/C=1-346.
DR PDBsum; 4JN6; -.
DR AlphaFoldDB; P9WMK5; -.
DR SMR; P9WMK5; -.
DR STRING; 83332.Rv3534c; -.
DR PaxDb; P9WMK5; -.
DR DNASU; 888387; -.
DR GeneID; 888387; -.
DR KEGG; mtu:Rv3534c; -.
DR TubercuList; Rv3534c; -.
DR eggNOG; COG0119; Bacteria.
DR OMA; DLYKMMD; -.
DR PhylomeDB; P9WMK5; -.
DR BioCyc; MetaCyc:G185E-7811-MON; -.
DR BRENDA; 4.1.3.39; 3445.
DR Proteomes; UP000001584; Chromosome.
DR GO; GO:0005829; C:cytosol; IBA:GO_Central.
DR GO; GO:0009274; C:peptidoglycan-based cell wall; HDA:MTBBASE.
DR GO; GO:0003852; F:2-isopropylmalate synthase activity; IBA:GO_Central.
DR GO; GO:0008701; F:4-hydroxy-2-oxovalerate aldolase activity; IEA:UniProtKB-UniRule.
DR GO; GO:0030145; F:manganese ion binding; IEA:UniProtKB-UniRule.
DR GO; GO:0019439; P:aromatic compound catabolic process; IEA:UniProtKB-UniRule.
DR GO; GO:0009098; P:leucine biosynthetic process; IBA:GO_Central.
DR CDD; cd07943; DRE_TIM_HOA; 1.
DR Gene3D; 3.20.20.70; -; 1.
DR HAMAP; MF_01656; HOA; 1.
DR InterPro; IPR017629; 4OH_2_O-val_aldolase.
DR InterPro; IPR013785; Aldolase_TIM.
DR InterPro; IPR012425; DmpG_comm.
DR InterPro; IPR035685; DRE_TIM_HOA.
DR InterPro; IPR000891; PYR_CT.
DR Pfam; PF07836; DmpG_comm; 1.
DR Pfam; PF00682; HMGL-like; 1.
DR TIGRFAMs; TIGR03217; 4OH_2_O_val_ald; 1.
DR PROSITE; PS50991; PYR_CT; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Aromatic hydrocarbons catabolism; Cobalt; Lyase; Manganese;
KW Metal-binding; Nickel; Reference proteome.
FT CHAIN 1..346
FT /note="4-hydroxy-2-oxohexanoate aldolase"
FT /id="PRO_0000387862"
FT DOMAIN 7..259
FT /note="Pyruvate carboxyltransferase"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01151"
FT ACT_SITE 19
FT /note="Proton acceptor"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_01656"
FT BINDING 15..16
FT /ligand="substrate"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_01656,
FT ECO:0000305|PubMed:23614353"
FT BINDING 16
FT /ligand="Mn(2+)"
FT /ligand_id="ChEBI:CHEBI:29035"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_01656,
FT ECO:0000269|PubMed:23614353"
FT BINDING 169
FT /ligand="substrate"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_01656,
FT ECO:0000305|PubMed:23614353"
FT BINDING 198
FT /ligand="Mn(2+)"
FT /ligand_id="ChEBI:CHEBI:29035"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_01656,
FT ECO:0000269|PubMed:23614353"
FT BINDING 198
FT /ligand="substrate"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_01656"
FT BINDING 200
FT /ligand="Mn(2+)"
FT /ligand_id="ChEBI:CHEBI:29035"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_01656,
FT ECO:0000269|PubMed:23614353"
FT BINDING 289
FT /ligand="substrate"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_01656,
FT ECO:0000305|PubMed:23614353"
FT SITE 15
FT /note="Transition state stabilizer"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_01656"
FT MUTAGEN 322
FT /note="G->F: Abolishes substrate channeling to HsaG."
FT /evidence="ECO:0000269|PubMed:23614353"
FT STRAND 6..14
FT /evidence="ECO:0007829|PDB:4JN6"
FT HELIX 16..20
FT /evidence="ECO:0007829|PDB:4JN6"
FT TURN 21..23
FT /evidence="ECO:0007829|PDB:4JN6"
FT HELIX 27..39
FT /evidence="ECO:0007829|PDB:4JN6"
FT STRAND 43..48
FT /evidence="ECO:0007829|PDB:4JN6"
FT TURN 58..60
FT /evidence="ECO:0007829|PDB:4JN6"
FT HELIX 67..77
FT /evidence="ECO:0007829|PDB:4JN6"
FT STRAND 79..87
FT /evidence="ECO:0007829|PDB:4JN6"
FT HELIX 94..102
FT /evidence="ECO:0007829|PDB:4JN6"
FT STRAND 107..113
FT /evidence="ECO:0007829|PDB:4JN6"
FT HELIX 117..120
FT /evidence="ECO:0007829|PDB:4JN6"
FT HELIX 121..129
FT /evidence="ECO:0007829|PDB:4JN6"
FT STRAND 133..140
FT /evidence="ECO:0007829|PDB:4JN6"
FT HELIX 141..143
FT /evidence="ECO:0007829|PDB:4JN6"
FT HELIX 146..158
FT /evidence="ECO:0007829|PDB:4JN6"
FT STRAND 162..168
FT /evidence="ECO:0007829|PDB:4JN6"
FT HELIX 176..189
FT /evidence="ECO:0007829|PDB:4JN6"
FT STRAND 194..200
FT /evidence="ECO:0007829|PDB:4JN6"
FT HELIX 206..215
FT /evidence="ECO:0007829|PDB:4JN6"
FT STRAND 220..224
FT /evidence="ECO:0007829|PDB:4JN6"
FT HELIX 225..227
FT /evidence="ECO:0007829|PDB:4JN6"
FT HELIX 237..246
FT /evidence="ECO:0007829|PDB:4JN6"
FT HELIX 255..264
FT /evidence="ECO:0007829|PDB:4JN6"
FT HELIX 267..269
FT /evidence="ECO:0007829|PDB:4JN6"
FT STRAND 270..272
FT /evidence="ECO:0007829|PDB:4JN6"
FT HELIX 278..286
FT /evidence="ECO:0007829|PDB:4JN6"
FT HELIX 292..303
FT /evidence="ECO:0007829|PDB:4JN6"
FT HELIX 307..316
FT /evidence="ECO:0007829|PDB:4JN6"
FT HELIX 325..338
FT /evidence="ECO:0007829|PDB:4JN6"
SQ SEQUENCE 346 AA; 36442 MW; FB8634AC62E222CE CRC64;
MTDMWDVRIT DTSLRDGSHH KRHQFTKDEV GAIVAALDAA GVPVIEVTHG DGLGGSSFNY
GFSKTPEQEL IKLAAATAKE ARIAFLMLPG VGTKDDIKEA RDNGGSICRI ATHCTEADVS
IQHFGLAREL GLETVGFLMM AHTIAPEKLA AQARIMADAG CQCVYVVDSA GALVLDGVAD
RVSALVAELG EDAQVGFHGH ENLGLGVANS VAAVRAGAKQ IDGSCRRFGA GAGNAPVEAL
IGVFDKIGVK TGIDFFDIAD AAEDVVRPAM PAECLLDRNA LIMGYSGVYS SFLKHAVRQA
ERYGVPASAL LHRAGQRKLI GGQEDQLIDI ALEIKRELDS GAAVTH
