DHPH_RHOSO
ID DHPH_RHOSO Reviewed; 356 AA.
AC Q59771;
DT 11-NOV-2015, integrated into UniProtKB/Swiss-Prot.
DT 01-DEC-2001, sequence version 2.
DT 03-AUG-2022, entry version 99.
DE RecName: Full=Phenylalanine dehydrogenase {ECO:0000303|PubMed:10029526, ECO:0000303|PubMed:10924111};
DE Short=PheDH;
DE EC=1.4.1.20 {ECO:0000269|PubMed:10924111, ECO:0000269|PubMed:8206922};
GN Name=pdh {ECO:0000303|PubMed:8206922, ECO:0000312|EMBL:AAA21461.1};
OS Rhodococcus sp.
OC Bacteria; Actinobacteria; Corynebacteriales; Nocardiaceae; Rhodococcus.
OX NCBI_TaxID=1831 {ECO:0000312|EMBL:AAA21461.1};
RN [1] {ECO:0000312|EMBL:AAA21461.1}
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], PROTEIN SEQUENCE OF 1-38; 90-95; 97-114
RP AND 300-312, FUNCTION, AND CATALYTIC ACTIVITY.
RC STRAIN=M4 {ECO:0000312|EMBL:AAA21461.1};
RX PubMed=8206922; DOI=10.1016/s0021-9258(17)33993-5;
RA Brunhuber N.M., Banerjee A., Jacobs W.R. Jr., Blanchard J.S.;
RT "Cloning, sequencing, and expression of Rhodococcus L-phenylalanine
RT dehydrogenase. Sequence comparisons to amino-acid dehydrogenases.";
RL J. Biol. Chem. 269:16203-16211(1994).
RN [2] {ECO:0007744|PDB:1BW9, ECO:0007744|PDB:1BXG}
RP X-RAY CRYSTALLOGRAPHY (1.50 ANGSTROMS) IN COMPLEXES WITH NAD;
RP PHENYLPROPIONATE AND KETO-PHENYLPYRUVATE, AND SUBUNIT.
RX PubMed=10029526; DOI=10.1021/bi982244q;
RA Vanhooke J.L., Thoden J.B., Brunhuber N.M., Blanchard J.S., Holden H.M.;
RT "Phenylalanine dehydrogenase from Rhodococcus sp. M4: high-resolution X-ray
RT analyses of inhibitory ternary complexes reveal key features in the
RT oxidative deamination mechanism.";
RL Biochemistry 38:2326-2339(1999).
RN [3] {ECO:0007744|PDB:1C1D, ECO:0007744|PDB:1C1X}
RP X-RAY CRYSTALLOGRAPHY (1.25 ANGSTROMS) OF 2-356 IN COMPLEX WITH NAD AND
RP SUBSTRATE, FUNCTION, PATHWAY, CATALYTIC ACTIVITY, ACTIVITY REGULATION,
RP SUBUNIT, BIOPHYSICOCHEMICAL PROPERTIES, AND ACTIVE SITE.
RX PubMed=10924111; DOI=10.1021/bi000494c;
RA Brunhuber N.M., Thoden J.B., Blanchard J.S., Vanhooke J.L.;
RT "Rhodococcus L-phenylalanine dehydrogenase: kinetics, mechanism, and
RT structural basis for catalytic specificity.";
RL Biochemistry 39:9174-9187(2000).
CC -!- FUNCTION: Catalyzes the reversible NAD(+)-dependent oxidative
CC deamination of L-phenylalanine to phenylpyruvate.
CC {ECO:0000269|PubMed:10924111, ECO:0000269|PubMed:8206922}.
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:10924111, ECO:0000269|PubMed:8206922};
CC -!- ACTIVITY REGULATION: Subject to competitive inhibition by 3-
CC phenylpropionate for the conversion of L-phenylalanine to
CC phenylpyruvate. Subject to competitive inhibition by D-phenylalanine
CC for the conversion of phenylpyruvate to L-phenylalanine.
CC {ECO:0000269|PubMed:10924111}.
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=1.4 mM for NAD in the forward reaction;
CC KM=0.03 mM for NADH in the reverse reaction;
CC KM=0.12 mM for phenylpyruvate in the reverse reaction;
CC KM=5.5 mM for L-phenylalanine in the forward reaction;
CC -!- PATHWAY: Amino-acid biosynthesis; L-phenylalanine biosynthesis; L-
CC phenylalanine from phenylpyruvate (PDH route): step 1/1.
CC {ECO:0000305|PubMed:10924111}.
CC -!- SUBUNIT: Homotetramer, dimer of dimers. {ECO:0000269|PubMed:10924111,
CC ECO:0000305|PubMed:10029526}.
CC -!- SIMILARITY: Belongs to the Glu/Leu/Phe/Val dehydrogenases family.
CC {ECO:0000255|RuleBase:RU004417}.
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DR EMBL; U08381; AAA21461.1; -; Genomic_DNA.
DR PIR; A54038; A54038.
DR PDB; 1BW9; X-ray; 1.50 A; A/B=1-356.
DR PDB; 1BXG; X-ray; 2.30 A; A/B=1-356.
DR PDB; 1C1D; X-ray; 1.25 A; A/B=2-356.
DR PDB; 1C1X; X-ray; 1.40 A; A/B=2-356.
DR PDBsum; 1BW9; -.
DR PDBsum; 1BXG; -.
DR PDBsum; 1C1D; -.
DR PDBsum; 1C1X; -.
DR AlphaFoldDB; Q59771; -.
DR SMR; Q59771; -.
DR DrugBank; DB02494; (S)-3-phenyllactic acid.
DR DrugBank; DB03884; Phenylpyruvic acid.
DR BRENDA; 1.4.1.20; 5397.
DR UniPathway; UPA00121; UER00346.
DR EvolutionaryTrace; Q59771; -.
DR GO; GO:0000166; F:nucleotide binding; IEA:UniProtKB-KW.
DR GO; GO:0050175; F:phenylalanine dehydrogenase activity; IDA:UniProtKB.
DR GO; GO:0009094; P:L-phenylalanine biosynthetic process; IEA:UniProtKB-UniPathway.
DR GO; GO:0006559; P:L-phenylalanine catabolic process; IDA:UniProtKB.
DR InterPro; IPR046346; Aminiacid_DH-like_N_sf.
DR InterPro; IPR006095; Glu/Leu/Phe/Val_DH.
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.
PE 1: Evidence at protein level;
KW 3D-structure; Direct protein sequencing; NAD; Nucleotide-binding;
KW Oxidoreductase.
FT INIT_MET 1
FT /note="Removed"
FT /evidence="ECO:0000269|PubMed:8206922"
FT CHAIN 2..356
FT /note="Phenylalanine dehydrogenase"
FT /id="PRO_0000434608"
FT ACT_SITE 79
FT /note="Proton donor/acceptor"
FT /evidence="ECO:0000305|PubMed:10924111"
FT BINDING 43
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000269|PubMed:10924111,
FT ECO:0007744|PDB:1C1D"
FT BINDING 67
FT /ligand="substrate"
FT /evidence="ECO:0000269|PubMed:10924111,
FT ECO:0007744|PDB:1C1D"
FT BINDING 118..119
FT /ligand="substrate"
FT /evidence="ECO:0000269|PubMed:10924111,
FT ECO:0007744|PDB:1C1D"
FT BINDING 119
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000269|PubMed:10924111,
FT ECO:0007744|PDB:1BXG, ECO:0007744|PDB:1C1D,
FT ECO:0007744|PDB:1C1X"
FT BINDING 150
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000269|PubMed:10924111,
FT ECO:0007744|PDB:1BXG, ECO:0007744|PDB:1C1D,
FT ECO:0007744|PDB:1C1X"
FT BINDING 154
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000269|PubMed:10924111,
FT ECO:0007744|PDB:1BXG, ECO:0007744|PDB:1C1D,
FT ECO:0007744|PDB:1C1X"
FT BINDING 183..189
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000269|PubMed:10924111, ECO:0000305,
FT ECO:0007744|PDB:1BW9, ECO:0007744|PDB:1BXG,
FT ECO:0007744|PDB:1C1D"
FT BINDING 206..207
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000269|PubMed:10924111,
FT ECO:0007744|PDB:1BW9, ECO:0007744|PDB:1BXG,
FT ECO:0007744|PDB:1C1D"
FT BINDING 211
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000269|PubMed:10924111,
FT ECO:0007744|PDB:1BW9, ECO:0007744|PDB:1BXG,
FT ECO:0007744|PDB:1C1D"
FT BINDING 240..241
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000269|PubMed:10924111,
FT ECO:0007744|PDB:1BW9, ECO:0007744|PDB:1BXG,
FT ECO:0007744|PDB:1C1D"
FT BINDING 261..263
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000269|PubMed:10924111,
FT ECO:0007744|PDB:1BW9, ECO:0007744|PDB:1BXG,
FT ECO:0007744|PDB:1C1D"
FT BINDING 263
FT /ligand="substrate"
FT /evidence="ECO:0000269|PubMed:10924111,
FT ECO:0007744|PDB:1C1D"
FT HELIX 3..7
FT /evidence="ECO:0007829|PDB:1C1D"
FT STRAND 11..19
FT /evidence="ECO:0007829|PDB:1C1D"
FT TURN 20..23
FT /evidence="ECO:0007829|PDB:1C1D"
FT STRAND 24..32
FT /evidence="ECO:0007829|PDB:1C1D"
FT STRAND 34..45
FT /evidence="ECO:0007829|PDB:1C1D"
FT HELIX 50..70
FT /evidence="ECO:0007829|PDB:1C1D"
FT STRAND 76..83
FT /evidence="ECO:0007829|PDB:1C1D"
FT HELIX 88..90
FT /evidence="ECO:0007829|PDB:1C1D"
FT HELIX 93..109
FT /evidence="ECO:0007829|PDB:1C1D"
FT TURN 110..112
FT /evidence="ECO:0007829|PDB:1C1D"
FT STRAND 113..118
FT /evidence="ECO:0007829|PDB:1C1D"
FT HELIX 124..133
FT /evidence="ECO:0007829|PDB:1C1D"
FT HELIX 142..144
FT /evidence="ECO:0007829|PDB:1C1D"
FT HELIX 151..168
FT /evidence="ECO:0007829|PDB:1C1D"
FT STRAND 178..182
FT /evidence="ECO:0007829|PDB:1C1D"
FT HELIX 186..197
FT /evidence="ECO:0007829|PDB:1C1D"
FT STRAND 201..205
FT /evidence="ECO:0007829|PDB:1C1D"
FT HELIX 209..217
FT /evidence="ECO:0007829|PDB:1C1D"
FT HELIX 225..230
FT /evidence="ECO:0007829|PDB:1C1D"
FT STRAND 234..238
FT /evidence="ECO:0007829|PDB:1C1D"
FT HELIX 247..252
FT /evidence="ECO:0007829|PDB:1C1D"
FT STRAND 256..258
FT /evidence="ECO:0007829|PDB:1C1D"
FT STRAND 266..268
FT /evidence="ECO:0007829|PDB:1C1X"
FT HELIX 269..277
FT /evidence="ECO:0007829|PDB:1C1D"
FT HELIX 285..288
FT /evidence="ECO:0007829|PDB:1C1D"
FT HELIX 291..300
FT /evidence="ECO:0007829|PDB:1C1D"
FT HELIX 306..314
FT /evidence="ECO:0007829|PDB:1C1D"
FT HELIX 316..330
FT /evidence="ECO:0007829|PDB:1C1D"
FT HELIX 334..348
FT /evidence="ECO:0007829|PDB:1C1D"
SQ SEQUENCE 356 AA; 36609 MW; A969C29E9466935E CRC64;
MSIDSALNWD GEMTVTRFDR ETGAHFVIRL DSTQLGPAAG GTRAAQYSQL ADALTDAGKL
AGAMTLKMAV SNLPMGGGKS VIALPAPRHS IDPSTWARIL RIHAENIDKL SGNYWTGPDV
NTNSADMDTL NDTTEFVFGR SLERGGAGSS AFTTAVGVFE AMKATVAHRG LGSLDGLTVL
VQGLGAVGGS LASLAAEAGA QLLVADTDTE RVAHAVALGH TAVALEDVLS TPCDVFAPCA
MGGVITTEVA RTLDCSVVAG AANNVIADEA ASDILHARGI LYAPDFVANA GGAIHLVGRE
VLGWSESVVH ERAVAIGDTL NQVFEISDND GVTPDEAART LAGRRAREAS TTTATA
