PH3H_STRC4
ID PH3H_STRC4 Reviewed; 279 AA.
AC F5BFC8;
DT 10-OCT-2018, integrated into UniProtKB/Swiss-Prot.
DT 28-JUN-2011, sequence version 1.
DT 03-AUG-2022, entry version 27.
DE RecName: Full=Phenylalanine 3-hydroxylase {ECO:0000303|PubMed:21615132};
DE Short=Phe3H {ECO:0000303|PubMed:21615132};
DE EC=1.14.16.7 {ECO:0000305|PubMed:21615132};
DE AltName: Full=Fe-dependent phenylalanine hydroxylase {ECO:0000303|PubMed:21615132};
DE AltName: Full=Phenylalanine 3-monooxygenase {ECO:0000305};
GN Name=pacX {ECO:0000303|PubMed:21417270}; Synonyms=phhA {ECO:0000303|Ref.2};
OS Streptomyces coeruleorubidus.
OC Bacteria; Actinobacteria; Streptomycetales; Streptomycetaceae;
OC Streptomyces.
OX NCBI_TaxID=116188;
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RC STRAIN=AB1183F-64 {ECO:0000312|EMBL:AFK26599.1};
RX PubMed=20665770; DOI=10.1002/cbic.201000200;
RA Rackham E.J., Gruschow S., Ragab A.E., Dickens S., Goss R.J.;
RT "Pacidamycin biosynthesis: identification and heterologous expression of
RT the first uridyl peptide antibiotic gene cluster.";
RL ChemBioChem 11:1700-1709(2010).
RN [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RC STRAIN=AB1183F-64 {ECO:0000312|EMBL:AFK26599.1};
RA Gruschow S., Rackham E.J., Goss R.J.M.;
RT "Diversity in natural product families is governed by more than enzyme
RT promiscuity alone: establishing control of the pacidamycin portfolio.";
RL Chem. Sci. 2:2182-2186(2011).
RN [3]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RX PubMed=21417270; DOI=10.1021/ja2011109;
RA Zhang W., Ntai I., Bolla M.L., Malcolmson S.J., Kahne D., Kelleher N.L.,
RA Walsh C.T.;
RT "Nine enzymes are required for assembly of the pacidamycin group of
RT peptidyl nucleoside antibiotics.";
RL J. Am. Chem. Soc. 133:5240-5243(2011).
RN [4]
RP FUNCTION, CATALYTIC ACTIVITY, BIOPHYSICOCHEMICAL PROPERTIES, COFACTOR,
RP MUTAGENESIS OF CYS-187 AND THR-202, AND SUBSTRATE SPECIFICITY.
RC STRAIN=NRRL 18370;
RX PubMed=21615132; DOI=10.1021/bi200733c;
RA Zhang W., Ames B.D., Walsh C.T.;
RT "Identification of phenylalanine 3-hydroxylase for meta-tyrosine
RT biosynthesis.";
RL Biochemistry 50:5401-5403(2011).
CC -!- FUNCTION: In vitro, catalyzes the highly regiospecific C-3
CC hydroxylation of L-phenylalanine (L-Phe) to yield 3-hydroxy-L-
CC phenylalanine (meta-Tyr), an amino acid found in bacterial secondary
CC metabolites such as sanglifehrin A and some pacidamycins.
CC Tetrahydrobiopterin (BH4) seems to be the physiological pterin, however
CC the hydroxylase is also able to use 6-methyltetrahydropterin (6-MePH4).
CC {ECO:0000269|PubMed:21615132}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=(6R)-L-erythro-5,6,7,8-tetrahydrobiopterin + L-phenylalanine +
CC O2 = (4aS,6R)-4a-hydroxy-L-erythro-5,6,7,8-tetrahydrobiopterin + 3-
CC hydroxy-L-phenylalanine; Xref=Rhea:RHEA:41532, ChEBI:CHEBI:15379,
CC ChEBI:CHEBI:15642, ChEBI:CHEBI:58095, ChEBI:CHEBI:59560,
CC ChEBI:CHEBI:78290; EC=1.14.16.7;
CC Evidence={ECO:0000305|PubMed:21615132};
CC -!- COFACTOR:
CC Name=Fe(2+); Xref=ChEBI:CHEBI:29033;
CC Evidence={ECO:0000269|PubMed:21615132};
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=1.1 mM for L-phenylalanine {ECO:0000269|PubMed:21615132};
CC KM=26 uM for 6-methyltetrahydropterin {ECO:0000269|PubMed:21615132};
CC Note=kcat is 1.3 min(-1) for L-phenylalanine as substrate. kcat is
CC 1.2 min(-1) for 6-methyltetrahydropterin as substrate.
CC {ECO:0000269|PubMed:21615132};
CC pH dependence:
CC Optimum pH is 6, and the enzyme tends to precipitate gradually below
CC pH 6.5. {ECO:0000269|PubMed:21615132};
CC -!- SIMILARITY: Belongs to the biopterin-dependent aromatic amino acid
CC hydroxylase family. {ECO:0000305}.
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DR EMBL; JN157766; AFK26599.1; -; Genomic_DNA.
DR EMBL; HQ874646; AEB33695.1; -; Genomic_DNA.
DR AlphaFoldDB; F5BFC8; -.
DR SMR; F5BFC8; -.
DR KEGG; ag:AEB33695; -.
DR BioCyc; MetaCyc:MON-17528; -.
DR BRENDA; 1.14.16.7; 13389.
DR GO; GO:0005506; F:iron ion binding; IEA:InterPro.
DR GO; GO:0016714; F:oxidoreductase activity, acting on paired donors, with incorporation or reduction of molecular oxygen, reduced pteridine as one donor, and incorporation of one atom of oxygen; IEA:InterPro.
DR GO; GO:0006559; P:L-phenylalanine catabolic process; IEA:UniProtKB-KW.
DR Gene3D; 1.10.800.10; -; 1.
DR InterPro; IPR001273; ArAA_hydroxylase.
DR InterPro; IPR036951; ArAA_hydroxylase_sf.
DR InterPro; IPR036329; Aro-AA_hydroxylase_C_sf.
DR InterPro; IPR019774; Aromatic-AA_hydroxylase_C.
DR PANTHER; PTHR11473; PTHR11473; 1.
DR Pfam; PF00351; Biopterin_H; 1.
DR PRINTS; PR00372; FYWHYDRXLASE.
DR SUPFAM; SSF56534; SSF56534; 1.
DR PROSITE; PS51410; BH4_AAA_HYDROXYL_2; 1.
PE 1: Evidence at protein level;
KW Iron; Metal-binding; Monooxygenase; Oxidoreductase;
KW Phenylalanine catabolism.
FT CHAIN 1..279
FT /note="Phenylalanine 3-hydroxylase"
FT /id="PRO_0000445425"
FT BINDING 140
FT /ligand="Fe cation"
FT /ligand_id="ChEBI:CHEBI:24875"
FT /evidence="ECO:0000250|UniProtKB:P04176"
FT BINDING 145
FT /ligand="Fe cation"
FT /ligand_id="ChEBI:CHEBI:24875"
FT /evidence="ECO:0000250|UniProtKB:P04176"
FT BINDING 186
FT /ligand="Fe cation"
FT /ligand_id="ChEBI:CHEBI:24875"
FT /evidence="ECO:0000250|UniProtKB:P04176"
FT SITE 187
FT /note="Important for the regiospecific hydroxylation of the
FT phenyl ring"
FT /evidence="ECO:0000269|PubMed:21615132"
FT SITE 202
FT /note="Important for the regiospecific hydroxylation of the
FT phenyl ring"
FT /evidence="ECO:0000269|PubMed:21615132"
FT MUTAGEN 187
FT /note="C->F: Loss of hydroxylase activity. Only a small
FT amount of 3-hydroxy-L-phenylalanine (meta-Tyr) is formed;
FT when associated with G-202."
FT /evidence="ECO:0000269|PubMed:21615132"
FT MUTAGEN 202
FT /note="T->G: 60-fold increase in the preference for 4-
FT hydroxy-L-phenylalanine (para-Tyr) over 3-hydroxy-L-
FT phenylalanine (meta-Tyr) formation. Only a small amount of
FT 3-hydroxy-L-phenylalanine (meta-Tyr) is formed; when
FT associated with F-187."
FT /evidence="ECO:0000269|PubMed:21615132"
SQ SEQUENCE 279 AA; 31038 MW; 455844FDACFCE73A CRC64;
MQGPHAQMTD AAYEIRRSEI AALSTDLAPE DPIPVVEYTE WEHEVWRTVC VDLTARHRTD
AAAEYLESAE QLAVPLDHVP QLRDVSGRLG SISGFTFQSA PALVPLREFC GGLANSVFHS
TQYLRHPRSP FYTEDPDLLH DLVGHGNVLA SDRFARLYRL AGNAAARVHS TEALQFIGKV
FWFTLECGVV RERGERKAYG ATLVSSYGEL DHFRSADFRP LDIKSLADVE YDISTYQPIL
FEADSMDEVE DTVGSFWDTC DDDSIAALLG GTSRSVTPH
