ACDH_MYCTU
ID ACDH_MYCTU Reviewed; 303 AA.
AC P9WQH3; L0TEF0; P71866; Q7D5C3;
DT 16-APR-2014, integrated into UniProtKB/Swiss-Prot.
DT 16-APR-2014, sequence version 1.
DT 03-AUG-2022, entry version 39.
DE RecName: Full=Propanal dehydrogenase (CoA-propanoylating) {ECO:0000305};
DE EC=1.2.1.87 {ECO:0000269|PubMed:23614353};
DE AltName: Full=Acetaldehyde dehydrogenase {ECO:0000255|HAMAP-Rule:MF_01657};
DE EC=1.2.1.10 {ECO:0000255|HAMAP-Rule:MF_01657, ECO:0000269|PubMed:23614353};
DE AltName: Full=Acetaldehyde dehydrogenase [acetylating] {ECO:0000255|HAMAP-Rule:MF_01657};
GN Name=hsaG {ECO:0000303|PubMed:23614353}; OrderedLocusNames=Rv3535c;
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 HSAF, FUNCTION,
RP CATALYTIC ACTIVITY, ACTIVITY REGULATION, BIOPHYSICOCHEMICAL PROPERTIES,
RP SUBUNIT, AND MUTAGENESIS OF SER-41.
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 conversion
CC of propanal to propanoyl-CoA, using NAD(+) and coenzyme A. Has a broad
CC substrate specificity, and can also use acetaldehyde, butyrlaldehyde,
CC isobutyrlaldehyde and pentaldehyde as substrates.
CC {ECO:0000269|PubMed:23614353}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=CoA + NAD(+) + propanal = H(+) + NADH + propanoyl-CoA;
CC Xref=Rhea:RHEA:36027, ChEBI:CHEBI:15378, ChEBI:CHEBI:17153,
CC ChEBI:CHEBI:57287, ChEBI:CHEBI:57392, ChEBI:CHEBI:57540,
CC ChEBI:CHEBI:57945; EC=1.2.1.87;
CC Evidence={ECO:0000269|PubMed:23614353};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:36028;
CC Evidence={ECO:0000269|PubMed:23614353};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=acetaldehyde + CoA + NAD(+) = acetyl-CoA + H(+) + NADH;
CC Xref=Rhea:RHEA:23288, ChEBI:CHEBI:15343, ChEBI:CHEBI:15378,
CC ChEBI:CHEBI:57287, ChEBI:CHEBI:57288, ChEBI:CHEBI:57540,
CC ChEBI:CHEBI:57945; EC=1.2.1.10; Evidence={ECO:0000255|HAMAP-
CC Rule:MF_01657, ECO:0000269|PubMed:23614353};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:23289;
CC Evidence={ECO:0000269|PubMed:23614353};
CC -!- ACTIVITY REGULATION: Unlike HsaF, HsaG is active both in the presence
CC and absence of its partner enzyme. {ECO:0000269|PubMed:23614353}.
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=18 mM for acetaldehyde (in the presence of HsaF)
CC {ECO:0000269|PubMed:23614353};
CC KM=21.3 mM for acetaldehyde (in the absence of HsaF)
CC {ECO:0000269|PubMed:23614353};
CC KM=15 mM for propanal (in the presence of HsaF)
CC {ECO:0000269|PubMed:23614353};
CC KM=12.4 mM for propanal (in the absence of HsaF)
CC {ECO:0000269|PubMed:23614353};
CC KM=10.6 mM for butyrlaldehyde (in the presence of HsaF)
CC {ECO:0000269|PubMed:23614353};
CC KM=10 mM for isobutyrlaldehyde (in the presence of HsaF)
CC {ECO:0000269|PubMed:23614353};
CC KM=20 mM for pentaldehyde (in the presence of HsaF)
CC {ECO:0000269|PubMed:23614353};
CC KM=0.040 mM for coenzyme A (in the presence of HsaF)
CC {ECO:0000269|PubMed:23614353};
CC KM=0.415 mM for coenzyme A (in the absence of HsaF)
CC {ECO:0000269|PubMed:23614353};
CC KM=0.022 mM for NAD(+) (in the presence or absence of HsaF)
CC {ECO:0000269|PubMed:23614353};
CC KM=1.4 mM for NADP(+) (in the presence of HsaF)
CC {ECO:0000269|PubMed:23614353};
CC Note=kcat is 9.4 sec(-1) with acetaldehyde as substrate (in the
CC presence of HsaF). kcat is 19.0 sec(-1) with acetaldehyde as
CC substrate (in the absence of HsaF). kcat is 11.1 sec(-1) with
CC propanal as substrate (in the presence of HsaF). kcat is 23.8 sec(-1)
CC with propanal as substrate (in the absence of HsaF). kcat is 7.3
CC sec(-1) with butyrlaldehyde as substrate. kcat is 5.8 sec(-1) with
CC isobutyrlaldehyde as substrate. kcat is 7.8 sec(-1) with pentaldehyde
CC as substrate. kcat is 9.6 sec(-1) with coenzyme A as substrate (in
CC the presence of HsaF). kcat is 15 sec(-1) with coenzyme A as
CC substrate (in the absence of HsaF). kcat is 7.6 sec(-1) with NAD(+)
CC as substrate (in the presence of HsaF). kcat is 3.9 sec(-1) with
CC NAD(+) as substrate (in the absence of HsaF). kcat is 3.4 sec(-1)
CC with NADP(+) as substrate. {ECO:0000269|PubMed:23614353};
CC -!- SUBUNIT: Monomer. Forms an heterotetramer composed of two aldolase
CC (HsaF) and two dehydrogenase (HsaG) subunits.
CC {ECO:0000269|PubMed:23614353}.
CC -!- SIMILARITY: Belongs to the acetaldehyde dehydrogenase family.
CC {ECO:0000255|HAMAP-Rule:MF_01657}.
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DR EMBL; AL123456; CCP46357.1; -; Genomic_DNA.
DR PIR; H70675; H70675.
DR RefSeq; NP_218052.1; NC_000962.3.
DR RefSeq; WP_003419251.1; NZ_NVQJ01000014.1.
DR PDB; 4JN6; X-ray; 1.93 A; B/D=1-303.
DR PDBsum; 4JN6; -.
DR AlphaFoldDB; P9WQH3; -.
DR SMR; P9WQH3; -.
DR STRING; 83332.Rv3535c; -.
DR SwissLipids; SLP:000001172; -.
DR PaxDb; P9WQH3; -.
DR DNASU; 888396; -.
DR GeneID; 45427519; -.
DR GeneID; 888396; -.
DR KEGG; mtu:Rv3535c; -.
DR PATRIC; fig|83332.111.peg.3940; -.
DR TubercuList; Rv3535c; -.
DR eggNOG; COG4569; Bacteria.
DR OMA; TSAYVHK; -.
DR PhylomeDB; P9WQH3; -.
DR BioCyc; MetaCyc:G185E-7812-MON; -.
DR Proteomes; UP000001584; Chromosome.
DR GO; GO:0008774; F:acetaldehyde dehydrogenase (acetylating) activity; IEA:UniProtKB-UniRule.
DR GO; GO:0051287; F:NAD binding; IEA:UniProtKB-UniRule.
DR GO; GO:0019439; P:aromatic compound catabolic process; IEA:UniProtKB-UniRule.
DR HAMAP; MF_01657; Ac_ald_DH_ac; 1.
DR InterPro; IPR003361; Acetaldehyde_dehydrogenase.
DR InterPro; IPR015426; Acetylaldehyde_DH_C.
DR InterPro; IPR036291; NAD(P)-bd_dom_sf.
DR InterPro; IPR000534; Semialdehyde_DH_NAD-bd.
DR Pfam; PF09290; AcetDehyd-dimer; 1.
DR Pfam; PF01118; Semialdhyde_dh; 1.
DR PIRSF; PIRSF015689; Actaldh_dh_actl; 1.
DR SMART; SM00859; Semialdhyde_dh; 1.
DR SUPFAM; SSF51735; SSF51735; 1.
DR TIGRFAMs; TIGR03215; ac_ald_DH_ac; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Aromatic hydrocarbons catabolism; NAD; Oxidoreductase;
KW Reference proteome.
FT CHAIN 1..303
FT /note="Propanal dehydrogenase (CoA-propanoylating)"
FT /id="PRO_0000387688"
FT ACT_SITE 127
FT /note="Acyl-thioester intermediate"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_01657"
FT BINDING 12..15
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_01657"
FT BINDING 158..166
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_01657"
FT BINDING 277
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_01657"
FT MUTAGEN 41
FT /note="S->D: 2200-fold decrease in catalytic efficiency
FT with coenzyme A."
FT /evidence="ECO:0000269|PubMed:23614353"
FT MUTAGEN 41
FT /note="S->I: 6600-fold decrease in catalytic efficiency
FT with coenzyme A."
FT /evidence="ECO:0000269|PubMed:23614353"
FT STRAND 5..10
FT /evidence="ECO:0007829|PDB:4JN6"
FT HELIX 14..24
FT /evidence="ECO:0007829|PDB:4JN6"
FT STRAND 27..35
FT /evidence="ECO:0007829|PDB:4JN6"
FT HELIX 42..49
FT /evidence="ECO:0007829|PDB:4JN6"
FT STRAND 53..57
FT /evidence="ECO:0007829|PDB:4JN6"
FT HELIX 59..62
FT /evidence="ECO:0007829|PDB:4JN6"
FT STRAND 70..74
FT /evidence="ECO:0007829|PDB:4JN6"
FT HELIX 78..91
FT /evidence="ECO:0007829|PDB:4JN6"
FT STRAND 94..97
FT /evidence="ECO:0007829|PDB:4JN6"
FT HELIX 109..116
FT /evidence="ECO:0007829|PDB:4JN6"
FT STRAND 120..123
FT /evidence="ECO:0007829|PDB:4JN6"
FT HELIX 127..140
FT /evidence="ECO:0007829|PDB:4JN6"
FT STRAND 148..155
FT /evidence="ECO:0007829|PDB:4JN6"
FT HELIX 156..158
FT /evidence="ECO:0007829|PDB:4JN6"
FT HELIX 161..165
FT /evidence="ECO:0007829|PDB:4JN6"
FT HELIX 167..180
FT /evidence="ECO:0007829|PDB:4JN6"
FT STRAND 185..194
FT /evidence="ECO:0007829|PDB:4JN6"
FT STRAND 202..210
FT /evidence="ECO:0007829|PDB:4JN6"
FT HELIX 216..231
FT /evidence="ECO:0007829|PDB:4JN6"
FT STRAND 237..241
FT /evidence="ECO:0007829|PDB:4JN6"
FT STRAND 244..246
FT /evidence="ECO:0007829|PDB:4JN6"
FT TURN 250..254
FT /evidence="ECO:0007829|PDB:4JN6"
FT STRAND 256..264
FT /evidence="ECO:0007829|PDB:4JN6"
FT STRAND 269..271
FT /evidence="ECO:0007829|PDB:4JN6"
FT HELIX 276..295
FT /evidence="ECO:0007829|PDB:4JN6"
SQ SEQUENCE 303 AA; 32009 MW; D52F1BEA88A56827 CRC64;
MPSKAKVAIV GSGNISTDLL YKLLRSEWLE PRWMVGIDPE SDGLARAAKL GLETTHEGVD
WLLAQPDKPD LVFEATSAYV HRDAAPKYAE AGIRAIDLTP AAVGPAVIPP ANLREHLDAP
NVNMITCGGQ ATIPIVYAVS RIVEVPYAEI VASVASVSAG PGTRANIDEF TKTTARGVQT
IGGAARGKAI IILNPADPPM IMRDTIFCAI PTDADREAIA ASIHDVVKEV QTYVPGYRLL
NEPQFDEPSI NSGGQALVTT FVEVEGAGDY LPPYAGNLDI MTAAATKVGE EIAKETLVVG
GAR
