DHPH_BACBA
ID DHPH_BACBA Reviewed; 380 AA.
AC Q59224;
DT 01-DEC-2000, integrated into UniProtKB/Swiss-Prot.
DT 01-NOV-1996, sequence version 1.
DT 03-AUG-2022, entry version 85.
DE RecName: Full=Phenylalanine dehydrogenase {ECO:0000303|PubMed:29051071, ECO:0000303|PubMed:8535000};
DE Short=PheDH {ECO:0000303|PubMed:29051071, ECO:0000303|PubMed:8535000};
DE EC=1.4.1.20 {ECO:0000269|PubMed:29051071};
GN Name=pdh {ECO:0000303|PubMed:8535000};
OS Bacillus badius.
OC Bacteria; Firmicutes; Bacilli; Bacillales; Bacillaceae; Bacillus.
OX NCBI_TaxID=1455;
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND PARTIAL PROTEIN SEQUENCE.
RC STRAIN=ATCC 14574 / DSM 23 / CCUG 7412 / IAM 11059 / NCIMB 9364 / NCTC
RC 10333 / NRS 663;
RX PubMed=8535000; DOI=10.1271/bbb.59.1994;
RA Yamada A., Dairi T., Ohno Y., Huang X., Asano Y.;
RT "Nucleotide sequencing of phenylalanine dehydrogenase gene from Bacillus
RT badius IAM 11059.";
RL Biosci. Biotechnol. Biochem. 59:1994-1995(1995).
RN [2]
RP FUNCTION, CATALYTIC ACTIVITY, SUBSTRATE SPECIFICITY, BIOPHYSICOCHEMICAL
RP PROPERTIES, MUTAGENESIS OF VAL-144, 3D-STRUCTURE MODELING, AND
RP BIOTECHNOLOGY.
RX PubMed=29051071; DOI=10.1016/j.abb.2017.10.009;
RA Yousefi F., Ataei F., Arab S.S., Hosseinkhani S.;
RT "Increase of Bacillus badius phenylalanine dehydrogenase specificity
RT towards phenylalanine substrate by site-directed mutagenesis.";
RL Arch. Biochem. Biophys. 635:44-51(2017).
CC -!- FUNCTION: Catalyzes the reversible NAD(+)-dependent oxidative
CC deamination of L-phenylalanine to phenylpyruvate. Is also able to act
CC on L-tyrosine, but with 100-fold lower efficiency.
CC {ECO:0000269|PubMed:29051071}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=H2O + L-phenylalanine + NAD(+) = 3-phenylpyruvate + H(+) +
CC NADH + NH4(+); Xref=Rhea:RHEA:21408, ChEBI:CHEBI:15377,
CC ChEBI:CHEBI:15378, ChEBI:CHEBI:18005, ChEBI:CHEBI:28938,
CC ChEBI:CHEBI:57540, ChEBI:CHEBI:57945, ChEBI:CHEBI:58095; EC=1.4.1.20;
CC Evidence={ECO:0000269|PubMed:29051071};
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=80 uM for L-phenylalanine {ECO:0000269|PubMed:29051071};
CC KM=8.6 mM for L-tyrosine {ECO:0000269|PubMed:29051071};
CC Note=kcat is 50 sec(-1) with L-phenylalanine as substrate. kcat is 58
CC sec(-1) with L-tyrosine as substrate. {ECO:0000269|PubMed:29051071};
CC -!- PATHWAY: Amino-acid biosynthesis; L-phenylalanine biosynthesis; L-
CC phenylalanine from phenylpyruvate (PDH route): step 1/1.
CC {ECO:0000305|PubMed:29051071}.
CC -!- BIOTECHNOLOGY: Phenylalanine dehydrogenase (PheDH) is a key enzyme in
CC medical diagnostic for determining the amount of phenylalanine to
CC detect phenylketonuria (PKU) disease. The mutant V144L has a higher
CC specificity for phenylalanine substrate and may provide a suitable
CC candidate to increase the specificity of PKU detection in clinic.
CC {ECO:0000305|PubMed:29051071}.
CC -!- SIMILARITY: Belongs to the Glu/Leu/Phe/Val dehydrogenases family.
CC {ECO:0000305}.
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DR EMBL; D50261; BAA08816.1; -; Genomic_DNA.
DR PIR; JC4328; JC4328.
DR AlphaFoldDB; Q59224; -.
DR SMR; Q59224; -.
DR STRING; 1455.SD78_0442; -.
DR KEGG; ag:BAA08816; -.
DR SABIO-RK; Q59224; -.
DR UniPathway; UPA00121; UER00346.
DR GO; GO:0000166; F:nucleotide binding; IEA:UniProtKB-KW.
DR GO; GO:0050175; F:phenylalanine dehydrogenase activity; IEA:UniProtKB-EC.
DR GO; GO:0009094; P:L-phenylalanine biosynthetic process; IEA:UniProtKB-UniPathway.
DR InterPro; IPR046346; Aminiacid_DH-like_N_sf.
DR InterPro; IPR006095; Glu/Leu/Phe/Val_DH.
DR InterPro; IPR033524; Glu/Leu/Phe/Val_DH_AS.
DR InterPro; IPR006096; Glu/Leu/Phe/Val_DH_C.
DR InterPro; IPR006097; Glu/Leu/Phe/Val_DH_dimer_dom.
DR InterPro; IPR016211; Glu/Phe/Leu/Val_DH_bac/arc.
DR InterPro; IPR036291; NAD(P)-bd_dom_sf.
DR PANTHER; PTHR42722; PTHR42722; 1.
DR Pfam; PF00208; ELFV_dehydrog; 1.
DR Pfam; PF02812; ELFV_dehydrog_N; 1.
DR PIRSF; PIRSF000188; Phe_leu_dh; 1.
DR PRINTS; PR00082; GLFDHDRGNASE.
DR SMART; SM00839; ELFV_dehydrog; 1.
DR SUPFAM; SSF51735; SSF51735; 1.
DR SUPFAM; SSF53223; SSF53223; 1.
DR PROSITE; PS00074; GLFV_DEHYDROGENASE; 1.
PE 1: Evidence at protein level;
KW Direct protein sequencing; NAD; Nucleotide-binding; Oxidoreductase.
FT INIT_MET 1
FT /note="Removed"
FT /evidence="ECO:0000305|PubMed:8535000"
FT CHAIN 2..380
FT /note="Phenylalanine dehydrogenase"
FT /id="PRO_0000182806"
FT ACT_SITE 90
FT /note="Proton donor/acceptor"
FT /evidence="ECO:0000250|UniProtKB:Q59771"
FT BINDING 54
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000250|UniProtKB:Q59771"
FT BINDING 78
FT /ligand="substrate"
FT /evidence="ECO:0000250|UniProtKB:Q59771"
FT BINDING 125
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000250|UniProtKB:Q59771"
FT BINDING 156
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000250|UniProtKB:Q59771"
FT BINDING 160
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000250|UniProtKB:Q59771"
FT BINDING 190..196
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000250|UniProtKB:Q59771"
FT BINDING 213..214
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000250|UniProtKB:Q59771"
FT BINDING 253..254
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000250|UniProtKB:Q59771"
FT BINDING 274..276
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000250|UniProtKB:Q59771"
FT BINDING 276
FT /ligand="substrate"
FT /evidence="ECO:0000250|UniProtKB:Q59771"
FT MUTAGEN 144
FT /note="V->D: 3-fold decrease in catalytic efficiency with
FT L-phenylalanine, and 7-fold decrease in catalytic
FT efficiency with L-tyrosine."
FT /evidence="ECO:0000269|PubMed:29051071"
FT MUTAGEN 144
FT /note="V->L: 2-fold increase in affinity for L-
FT phenylalanine. Slight increase in catalytic efficiency with
FT L-phenylalanine, while 3-fold decrease in catalytic
FT efficiency with L-tyrosine, leading to an increase in the
FT specificity ratio of phenylalanine over tyrosine by more
FT than 4-folds."
FT /evidence="ECO:0000269|PubMed:29051071"
FT MUTAGEN 144
FT /note="V->N: 5-fold decrease in catalytic efficiency with
FT L-phenylalanine, while 2-fold increase in catalytic
FT efficiency with L-tyrosine."
FT /evidence="ECO:0000269|PubMed:29051071"
SQ SEQUENCE 380 AA; 41353 MW; ABB94657BA6A109A CRC64;
MSLVEKTSII KDFTLFEKMS EHEQVVFCND PATGLRAIIA IHDTTLGPAL GGCRMQPYNS
VEEALEDALR LSKGMTYKCA ASDVDFGGGK AVIIGDPQKD KSPELFRAFG QFVDSLGGRF
YTGTDMGTNM EDFIHAMKET NCIVGVPEAY GGGGDSSIPT AMGVLYGIKA TNKMLFGKDD
LGGVTYAIQG LGKVGYKVAE GLLEEGAHLF VTDINEQTLE AIQEKAKTTS GSVTVVASDE
IYSQEADVFV PCAFGGVVND ETMKQFKVKA IAGSANNQLL TEDHGRHLAD KGILYAPDYI
VNSGGLIQVA DELYEVNKER VLAKTKHIYD AILEVYQQAE LDQITTMEAA NRMCEQRMAA
RGRRNSFFTS SVKPKWDIRN
