ID   ACDH4_PARXL             Reviewed;         304 AA.
AC   Q79AF6; Q13FT9;
DT   03-NOV-2009, integrated into UniProtKB/Swiss-Prot.
DT   05-JUL-2004, sequence version 1.
DT   27-MAR-2024, entry version 117.
DE   RecName: Full=Acetaldehyde dehydrogenase 4;
DE            EC=1.2.1.10;
DE   AltName: Full=Acetaldehyde dehydrogenase [acetylating] 4;
DE   AltName: Full=Propanal dehydrogenase (CoA-propanoylating);
DE            EC=1.2.1.87;
GN   Name=bphJ; OrderedLocusNames=Bxeno_C1122; ORFNames=Bxe_C1188;
OS   Paraburkholderia xenovorans (strain LB400).
OC   Bacteria; Pseudomonadota; Betaproteobacteria; Burkholderiales;
OC   Burkholderiaceae; Paraburkholderia.
OX   NCBI_TaxID=266265;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RX   PubMed=8026764; DOI=10.1016/0378-1119(94)90196-1;
RA   Hofer B., Backhaus S., Timmis K.N.;
RT   "The biphenyl/polychlorinated biphenyl-degradation locus (bph) of
RT   Pseudomonas sp. LB400 encodes four additional metabolic enzymes.";
RL   Gene 144:9-16(1994).
RN   [2]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC   STRAIN=LB400;
RX   PubMed=17030797; DOI=10.1073/pnas.0606924103;
RA   Chain P.S.G., Denef V.J., Konstantinidis K.T., Vergez L.M., Agullo L.,
RA   Reyes V.L., Hauser L., Cordova M., Gomez L., Gonzalez M., Land M., Lao V.,
RA   Larimer F., LiPuma J.J., Mahenthiralingam E., Malfatti S.A., Marx C.J.,
RA   Parnell J.J., Ramette A., Richardson P., Seeger M., Smith D., Spilker T.,
RA   Sul W.J., Tsoi T.V., Ulrich L.E., Zhulin I.B., Tiedje J.M.;
RT   "Burkholderia xenovorans LB400 harbors a multi-replicon, 9.73-Mbp genome
RT   shaped for versatility.";
RL   Proc. Natl. Acad. Sci. U.S.A. 103:15280-15287(2006).
RN   [3]
RP   FUNCTION, CATALYTIC ACTIVITY, SUBSTRATE SPECIFICITY, BIOPHYSICOCHEMICAL
RP   PROPERTIES, SUBUNIT, AND COMPLEX WITH BPHI.
RX   PubMed=19476337; DOI=10.1021/bi9006644;
RA   Baker P., Pan D., Carere J., Rossi A., Wang W., Seah S.Y.K.;
RT   "Characterization of an aldolase-dehydrogenase complex that exhibits
RT   substrate channeling in the polychlorinated biphenyls degradation
RT   pathway.";
RL   Biochemistry 48:6551-6558(2009).
RN   [4]
RP   FUNCTION, AND ACTIVITY REGULATION.
RX   PubMed=20364820; DOI=10.1021/bi100251u;
RA   Wang W., Baker P., Seah S.Y.;
RT   "Comparison of two metal-dependent pyruvate aldolases related by convergent
RT   evolution: substrate specificity, kinetic mechanism, and substrate
RT   channeling.";
RL   Biochemistry 49:3774-3782(2010).
RN   [5]
RP   MUTAGENESIS OF ILE-195, AND ALDEHYDE CHANNELING MECHANISM.
RC   STRAIN=LB400;
RX   PubMed=21838275; DOI=10.1021/bi200960j;
RA   Carere J., Baker P., Seah S.Y.;
RT   "Investigating the molecular determinants for substrate channeling in BphI-
RT   BphJ, an aldolase-dehydrogenase complex from the polychlorinated biphenyls
RT   degradation pathway.";
RL   Biochemistry 50:8407-8416(2011).
RN   [6]
RP   CATALYTIC ACTIVITY, SUBSTRATE SPECIFICITY, ACTIVE SITE, REACTION MECHANISM,
RP   AND MUTAGENESIS OF CYS-131; ASN-170; ILE-171; ILE-195 AND ASP-208.
RC   STRAIN=LB400;
RX   PubMed=22574886; DOI=10.1021/bi300407y;
RA   Baker P., Carere J., Seah S.Y.;
RT   "Substrate specificity, substrate channeling, and allostery in BphJ: an
RT   acylating aldehyde dehydrogenase associated with the pyruvate aldolase
RT   BphI.";
RL   Biochemistry 51:4558-4567(2012).
CC   -!- FUNCTION: Catalyzes the conversion of acetaldehyde or propanal to
CC       acetyl-CoA or propanoyl-CoA, respectively, using NAD(+) and coenzyme A.
CC       Displays broad specificity since it can utilize aliphatic aldehydes
CC       from two to five carbons in length as substrates; the aldehyde
CC       substrates can be directly channeled from the aldolase BphI to the
CC       dehydrogenase BphJ. Is the final enzyme in the meta-cleavage pathway
CC       for the degradation of polychlorinated biphenyls (PCBs). Is also able
CC       to utilize NADP(+) instead of NAD(+). Is not active with succinic
CC       semialdehyde or picolinaldehyde as substrates. Can also catalyze the
CC       reverse reaction, i.e. the reductive deacylation of acetyl-CoA to
CC       acetaldehyde, which is then channeled to the BphI active site. The
CC       BphI-BphJ enzyme complex exhibits unique bidirectionality in substrate
CC       channeling and allosteric activation. {ECO:0000269|PubMed:19476337,
CC       ECO:0000269|PubMed:20364820}.
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;
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   -!- ACTIVITY REGULATION: Bound pyruvate or other intermediates in the aldol
CC       addition reaction catalyzed by BphI allosterically activates BphJ
CC       reductive deacylation activity. {ECO:0000269|PubMed:20364820}.
CC   -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC       Kinetic parameters:
CC         KM=23.6 mM for acetaldehyde (at pH 8 and 25 degrees Celsius)
CC         {ECO:0000269|PubMed:19476337};
CC         KM=23.1 mM for propanaldehyde (at pH 8 and 25 degrees Celsius)
CC         {ECO:0000269|PubMed:19476337};
CC         KM=31.7 mM for butyraldehyde (at pH 8 and 25 degrees Celsius)
CC         {ECO:0000269|PubMed:19476337};
CC         KM=7.7 mM for isobutyraldehyde (at pH 8 and 25 degrees Celsius)
CC         {ECO:0000269|PubMed:19476337};
CC         KM=34.8 uM for NAD(+) (at pH 8 and 25 degrees Celsius)
CC         {ECO:0000269|PubMed:19476337};
CC         KM=561 uM for NADP(+) (at pH 8 and 25 degrees Celsius)
CC         {ECO:0000269|PubMed:19476337};
CC         Note=kcat is 17.2 and 16.3 sec(-1) with acetaldehyde and
CC         propanaldehyde as substrate, respectively (at pH 8 and 25 degrees
CC         Celsius).;
CC   -!- PATHWAY: Xenobiotic degradation; polychlorinated biphenyl degradation.
CC   -!- SUBUNIT: Heterotetramer composed of two BphI (aldolase) and two BphJ
CC       (dehydrogenase). {ECO:0000269|PubMed:19476337}.
CC   -!- SIMILARITY: Belongs to the acetaldehyde dehydrogenase family.
CC       {ECO:0000305}.
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DR   EMBL; CP000272; ABE37050.1; -; Genomic_DNA.
DR   EMBL; X76500; CAA54035.1; -; Genomic_DNA.
DR   RefSeq; WP_003450975.1; NZ_CP008761.1.
DR   AlphaFoldDB; Q79AF6; -.
DR   SMR; Q79AF6; -.
DR   STRING; 266265.Bxe_C1188; -.
DR   KEGG; bxb:DR64_8617; -.
DR   KEGG; bxe:Bxe_C1188; -.
DR   eggNOG; COG4569; Bacteria.
DR   OrthoDB; 9786743at2; -.
DR   BRENDA; 1.2.1.10; 7691.
DR   BRENDA; 1.2.1.87; 7691.
DR   SABIO-RK; Q79AF6; -.
DR   UniPathway; UPA01002; -.
DR   Proteomes; UP000001817; Chromosome 3.
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   Gene3D; 3.40.50.720; NAD(P)-binding Rossmann-like Domain; 1.
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   NCBIfam; TIGR03215; ac_ald_DH_ac; 1.
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; SSF55347; Glyceraldehyde-3-phosphate dehydrogenase-like, C-terminal domain; 1.
DR   SUPFAM; SSF51735; NAD(P)-binding Rossmann-fold domains; 1.
PE   1: Evidence at protein level;
KW   Allosteric enzyme; Aromatic hydrocarbons catabolism; NAD; NADP;
KW   Oxidoreductase.
FT   CHAIN           1..304
FT                   /note="Acetaldehyde dehydrogenase 4"
FT                   /id="PRO_0000387931"
FT   ACT_SITE        131
FT                   /note="Acyl-thioester intermediate"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_01657,
FT                   ECO:0000269|PubMed:22574886"
FT   BINDING         162..170
FT                   /ligand="NAD(+)"
FT                   /ligand_id="ChEBI:CHEBI:57540"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_01657"
FT   BINDING         273
FT                   /ligand="NAD(+)"
FT                   /ligand_id="ChEBI:CHEBI:57540"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_01657"
FT   SITE            195
FT                   /note="Responsible for governing aldehyde substrate chain
FT                   length specificity"
FT   MUTAGEN         131
FT                   /note="C->A,S: Loss of catalytic activity. Still able to
FT                   bind NAD(+), however with much lower affinity."
FT                   /evidence="ECO:0000269|PubMed:22574886"
FT   MUTAGEN         170
FT                   /note="N->A,D: Displays significant reduction in the level
FT                   of allosteric activation of the aldol cleavage reaction by
FT                   BphI."
FT                   /evidence="ECO:0000269|PubMed:22574886"
FT   MUTAGEN         171
FT                   /note="I->A,F: Exhibits preferences for aldehydes similar
FT                   as wild-type. Exhibits about 80% of wild-type acetaldehyde
FT                   channeling efficiency. Displays significant reduction in
FT                   the level of allosteric activation of the aldol cleavage
FT                   reaction by BphI."
FT                   /evidence="ECO:0000269|PubMed:22574886"
FT   MUTAGEN         195
FT                   /note="I->A: 5-fold decrease in affinity for acetaldehyde.
FT                   Increase in affinity for butyraldehyde and pentaldehyde,
FT                   leading to a 9- and 20-fold increase in catalytic
FT                   efficiency with butyraldehyde and pentaldehyde as
FT                   substrate, respectively. Exhibits 84% of wild-type
FT                   acetaldehyde channeling efficiency."
FT                   /evidence="ECO:0000269|PubMed:21838275,
FT                   ECO:0000269|PubMed:22574886"
FT   MUTAGEN         195
FT                   /note="I->F: 4- to 7-fold decrease in catalytic efficiency
FT                   with aldehydes three to four carbons in length. Does not
FT                   significantly reduce the channeling efficiency of the
FT                   enzyme complex toward acetaldehyde or propanaldehyde."
FT                   /evidence="ECO:0000269|PubMed:21838275,
FT                   ECO:0000269|PubMed:22574886"
FT   MUTAGEN         195
FT                   /note="I->L: Does not significantly reduce the channeling
FT                   efficiency of the enzyme complex toward acetaldehyde or
FT                   propanaldehyde."
FT                   /evidence="ECO:0000269|PubMed:21838275,
FT                   ECO:0000269|PubMed:22574886"
FT   MUTAGEN         195
FT                   /note="I->W: 5- to 16-fold decrease in catalytic efficiency
FT                   with aldehydes two to four carbons in length. Exhibits 59%
FT                   of wild-type acetaldehyde channeling efficiency."
FT                   /evidence="ECO:0000269|PubMed:21838275,
FT                   ECO:0000269|PubMed:22574886"
FT   MUTAGEN         208
FT                   /note="D->A: 2-fold decrease in catalytic efficiency."
FT                   /evidence="ECO:0000269|PubMed:22574886"
SQ   SEQUENCE   304 AA;  32237 MW;  3E9DDD9192B7D1AF CRC64;
     MTKKIKCALI GPGNIGTDLL AKLQRSPVLE PIWMVGIDPE SDGLKRAREM GIKTTADGVD
     GLIPHMQADG VQIVFDATSA YVHADNSRKV NALGALMIDL TPAAIGPFCV PTVNLKEHVG
     KGEMNVNMVT CGGQATIPMV AAVSRVQPVA YGEIVATVSS KSAGPGTRKN IDEFTRTTAG
     AVEKVGGAKK GKAIIILNPA EPPLIMRDTV HCLLESEPDQ AKITESIHAM IKEVQKYVPG
     YKLVNGPVFD GLRVSVYLEV EGLGDYLPKY AGNLDIMTAA AARTAEMFAE EILAGQLTLQ
     PVHA
//