ACDH4_PARXL
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 03-AUG-2022, entry version 111.
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; Proteobacteria; 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 EnsemblBacteria; ABE37050; ABE37050; Bxe_C1188.
DR KEGG; bxb:DR64_8617; -.
DR KEGG; bxe:Bxe_C1188; -.
DR eggNOG; COG4569; Bacteria.
DR OMA; LMMRDTI; -.
DR OrthoDB; 1432332at2; -.
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 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 Allosteric enzyme; Aromatic hydrocarbons catabolism; NAD; NADP;
KW Oxidoreductase; Reference proteome.
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
