HPDL_CLODI
ID HPDL_CLODI Reviewed; 902 AA.
AC Q84F16;
DT 11-JAN-2011, integrated into UniProtKB/Swiss-Prot.
DT 01-JUN-2003, sequence version 1.
DT 03-AUG-2022, entry version 67.
DE RecName: Full=4-hydroxyphenylacetate decarboxylase glycyl radical subunit {ECO:0000303|PubMed:16878993};
DE Short=HPA decarboxylase glycyl radical subunit;
DE EC=4.1.1.83 {ECO:0000269|PubMed:11231288, ECO:0000269|PubMed:16878993};
DE AltName: Full=4-hydroxyphenylacetate decarboxylase catalytic beta subunit {ECO:0000250|UniProtKB:Q38HX4};
DE AltName: Full=4-hydroxyphenylacetate decarboxylase large subunit {ECO:0000303|PubMed:16878993};
DE AltName: Full=p-hydroxyphenylacetate decarboxylase large subunit {ECO:0000303|PubMed:15153112};
GN Name=hpdB {ECO:0000312|EMBL:CAD65889.1};
OS Clostridioides difficile (Peptoclostridium difficile).
OC Bacteria; Firmicutes; Clostridia; Eubacteriales; Peptostreptococcaceae;
OC Clostridioides.
OX NCBI_TaxID=1496;
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], SUBUNIT, AND ACTIVATION BY HPDA.
RC STRAIN=ATCC 9689 / DSM 1296 / BCRC 10642 / JCM 1296 / NCIMB 10666 / NCTC
RC 11209 / 90556-M6S {ECO:0000312|EMBL:CAD65889.1};
RX PubMed=15153112; DOI=10.1111/j.1432-1033.2004.04152.x;
RA Andrei P.I., Pierik A.J., Zauner S., Andrei-Selmer L.C., Selmer T.;
RT "Subunit composition of the glycyl radical enzyme p-hydroxyphenylacetate
RT decarboxylase. A small subunit, HpdC, is essential for catalytic
RT activity.";
RL Eur. J. Biochem. 271:2225-2230(2004).
RN [2]
RP PROTEIN SEQUENCE OF 2-15, FUNCTION, CATALYTIC ACTIVITY, BIOPHYSICOCHEMICAL
RP PROPERTIES, ACTIVITY REGULATION, AND REACTION MECHANISM.
RC STRAIN=ATCC 9689 / DSM 1296 / BCRC 10642 / JCM 1296 / NCIMB 10666 / NCTC
RC 11209 / 90556-M6S {ECO:0000269|PubMed:11231288};
RX PubMed=11231288; DOI=10.1046/j.1432-1327.2001.02001.x;
RA Selmer T., Andrei P.I.;
RT "p-Hydroxyphenylacetate decarboxylase from Clostridium difficile. A novel
RT glycyl radical enzyme catalysing the formation of p-cresol.";
RL Eur. J. Biochem. 268:1363-1372(2001).
RN [3]
RP FUNCTION, CATALYTIC ACTIVITY, BIOPHYSICOCHEMICAL PROPERTIES, ACTIVATION BY
RP HPDA, SUBUNIT, AND SERINE PHOSPHORYLATION.
RC STRAIN=ATCC 9689 / DSM 1296 / BCRC 10642 / JCM 1296 / NCIMB 10666 / NCTC
RC 11209 / 90556-M6S {ECO:0000269|PubMed:16878993};
RX PubMed=16878993; DOI=10.1021/bi060840b;
RA Yu L., Blaser M., Andrei P.I., Pierik A.J., Selmer T.;
RT "4-Hydroxyphenylacetate decarboxylases: properties of a novel subclass of
RT glycyl radical enzyme systems.";
RL Biochemistry 45:9584-9592(2006).
CC -!- FUNCTION: Glycyl radical subunit of the HPA decarboxylase that
CC decarboxylates phenylacetates with a hydroxyl group in the p-position.
CC Active toward 4-hydroxyphenylacetate, 3,4-dihydroxyphenylacetate and to
CC a lesser extent p-hydroxymandelate (2-hydroxy-2-(4-
CC hydroxyphenyl)acetate), forming 4-methylphenol, 4-methylcatechol and 4-
CC hydroxybenzylalcohol, respectively. Is likely involved in the
CC catabolism of aromatic amino acids such as tyrosine fermentation. 4-
CC methylphenol (p-cresol) formation provides metabolic toxicity, which
CC may benefit the pathogen C.difficile by suppression of the endogenous
CC gastrointestinal microflora, allowing the development of
CC gastrointestinal infections (PubMed:11231288, PubMed:16878993). The
CC large subunit is the catalytic subunit that binds the substrate (By
CC similarity). {ECO:0000250|UniProtKB:Q38HX4,
CC ECO:0000269|PubMed:11231288, ECO:0000269|PubMed:16878993}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=4-hydroxyphenylacetate + H(+) = 4-methylphenol + CO2;
CC Xref=Rhea:RHEA:22732, ChEBI:CHEBI:15378, ChEBI:CHEBI:16526,
CC ChEBI:CHEBI:17847, ChEBI:CHEBI:48999; EC=4.1.1.83;
CC Evidence={ECO:0000269|PubMed:11231288, ECO:0000269|PubMed:16878993};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:22733;
CC Evidence={ECO:0000305|PubMed:11231288, ECO:0000305|PubMed:16878993};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=3,4-dihydroxyphenylacetate + H(+) = 4-methylcatechol + CO2;
CC Xref=Rhea:RHEA:62556, ChEBI:CHEBI:15378, ChEBI:CHEBI:16526,
CC ChEBI:CHEBI:17254, ChEBI:CHEBI:17612; EC=4.1.1.83;
CC Evidence={ECO:0000269|PubMed:11231288, ECO:0000269|PubMed:16878993};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:62557;
CC Evidence={ECO:0000305|PubMed:11231288, ECO:0000305|PubMed:16878993};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=2-hydroxy-2-(4-hydroxyphenyl)acetate + H(+) = 4-hydroxybenzyl
CC alcohol + CO2; Xref=Rhea:RHEA:62588, ChEBI:CHEBI:15378,
CC ChEBI:CHEBI:16526, ChEBI:CHEBI:32804, ChEBI:CHEBI:67410;
CC Evidence={ECO:0000269|PubMed:11231288};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:62589;
CC Evidence={ECO:0000305|PubMed:11231288};
CC -!- ACTIVITY REGULATION: Enzyme activity catalyzed by the HPA decarboxylase
CC complex is rapidly and irreversibly inactivated by oxygen.
CC Competitively inhibited by p-hydroxyphenylacetamide. Not inhibited by
CC m- or o-hydroxyphenyl-acetate, p-hydroxybenzoate or p-
CC hydroxyphenylpropionate. {ECO:0000269|PubMed:11231288}.
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=649 uM for 4-hydroxyphenylacetate {ECO:0000269|PubMed:16878993};
CC KM=410 uM for 3,4-dihydroxyphenylacetate
CC {ECO:0000269|PubMed:16878993};
CC Vmax=14.97 umol/min/mg enzyme for the decarboxylation of 4-
CC hydroxyphenylacetate {ECO:0000269|PubMed:16878993};
CC Vmax=8.82 umol/min/mg enzyme for the decarboxylation of 3,4-
CC hydroxyphenylacetate {ECO:0000269|PubMed:16878993};
CC Note=kcat is 110 sec(-1) for the decarboxylation of 4-
CC hydroxyphenylacetate. kcat is 65 sec(-1) for the decarboxylation of
CC 3,4-hydroxyphenylacetate. {ECO:0000269|PubMed:16878993};
CC pH dependence:
CC Optimum pH is 7.0. {ECO:0000269|PubMed:11231288};
CC Temperature dependence:
CC Has a half-life of 15 minutes at 30 degrees Celsius.
CC {ECO:0000269|PubMed:11231288};
CC -!- SUBUNIT: Heterooctamer consisting of 4 large (HpdB) subunits and 4
CC small (HpdC) subunits. Also forms a catalytically inactive homodimer.
CC {ECO:0000269|PubMed:15153112, ECO:0000269|PubMed:16878993}.
CC -!- PTM: Phosphorylated on serine. Phosphorylation may trigger the
CC formation of the active heterooctamers and thereby regulates enzyme
CC activity. {ECO:0000269|PubMed:16878993}.
CC -!- PTM: Requires the activating protein HpdA to generate the key active
CC site glycyl radical that is involved in catalysis.
CC {ECO:0000269|PubMed:15153112, ECO:0000269|PubMed:16878993}.
CC -!- SIMILARITY: Belongs to the glycyl radical enzyme (GRE) family. HPAD
CC subfamily. {ECO:0000305}.
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DR EMBL; AJ543425; CAD65889.1; -; Genomic_DNA.
DR RefSeq; WP_009895226.1; NZ_RRAL01000038.1.
DR AlphaFoldDB; Q84F16; -.
DR SMR; Q84F16; -.
DR KEGG; ag:CAD65889; -.
DR BioCyc; MetaCyc:MON-18507; -.
DR BRENDA; 4.1.1.83; 1473.
DR SABIO-RK; Q84F16; -.
DR GO; GO:0043722; F:4-hydroxyphenylacetate decarboxylase activity; IEA:UniProtKB-EC.
DR InterPro; IPR001150; Gly_radical.
DR InterPro; IPR004184; PFL_dom.
DR Pfam; PF01228; Gly_radical; 1.
DR Pfam; PF02901; PFL-like; 1.
DR PROSITE; PS51149; GLY_RADICAL_2; 1.
DR PROSITE; PS51554; PFL; 1.
PE 1: Evidence at protein level;
KW Direct protein sequencing; Lyase; Organic radical; Phosphoprotein.
FT INIT_MET 1
FT /note="Removed"
FT /evidence="ECO:0000269|PubMed:11231288"
FT CHAIN 2..902
FT /note="4-hydroxyphenylacetate decarboxylase glycyl radical
FT subunit"
FT /evidence="ECO:0000269|PubMed:11231288"
FT /id="PRO_5000070526"
FT DOMAIN 38..774
FT /note="PFL"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00887"
FT DOMAIN 782..902
FT /note="Glycine radical"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00493"
FT ACT_SITE 507
FT /note="Cysteine radical intermediate"
FT /evidence="ECO:0000250|UniProtKB:Q38HX4"
FT ACT_SITE 509
FT /note="Proton donor"
FT /evidence="ECO:0000250|UniProtKB:Q38HX4"
FT BINDING 348
FT /ligand="4-hydroxyphenylacetate"
FT /ligand_id="ChEBI:CHEBI:48999"
FT /evidence="ECO:0000250|UniProtKB:Q38HX4"
FT BINDING 507
FT /ligand="4-hydroxyphenylacetate"
FT /ligand_id="ChEBI:CHEBI:48999"
FT /evidence="ECO:0000250|UniProtKB:Q38HX4"
FT BINDING 540
FT /ligand="4-hydroxyphenylacetate"
FT /ligand_id="ChEBI:CHEBI:48999"
FT /evidence="ECO:0000250|UniProtKB:Q38HX4"
FT BINDING 641
FT /ligand="4-hydroxyphenylacetate"
FT /ligand_id="ChEBI:CHEBI:48999"
FT /evidence="ECO:0000250|UniProtKB:Q38HX4"
FT MOD_RES 877
FT /note="Glycine radical"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00493"
SQ SEQUENCE 902 AA; 101276 MW; 07F152C7CEBDF87C CRC64;
MSQSKEDKIR SILEAKNIKS NFQNKENLSE FNEKKASKRA EDLLDVYYNT LSTADMEFPY
WYNREYRKSD GDIPVVRRAK ALKAAFSHMT PNIIPGEKIV MQKTRHYRGS FPMPWVSESF
FVAQGEQMRE EAKKLASNTA DELTKFGSGG GNVTESFGNV VSIAGKFGMR KEEVPVLVKM
AKEWVGKSVE DLGFHYEKMM PDYDLKENLM STLICMFDSG YTLPQGREVI NYFYPLNYGL
DGIIEMAKEC KKAVAGNASG DGLIGMDRLY FYEAVIQVIE GLQTWILNYA KHAKYLESIE
TDLEAKKEYS DLVEILEHIA HKQPRTFREA LQLTYTIHIA SVNEDAISGM SIGRFGQILY
PWYEQDIEKG LITKEEVIEL LELYRIKITC IDCFASAGVN GGVLSGNTFN TLSIGGLKED
GSTGANELEE LLLEASMRCR TPQPSLTMLY DEKLPEDFLM KAAECTKLGS GYPAWVNNSN
GTTFMMKQFA DEGMTVEEAR AFALGGCLET SPGCWKQLTL NGKTYSIAGG AGQSAGSGVH
FIANPKILEL VLMNGKDYRM NIQVFEPHNK PLDTYEEVIE VFKDYYKQAI NVLERANNIE
LDIWRKFDTS IINSLLKPDC LDKGQHIGNM GYRYNATLNV ETCGTVTMVN SFAALKKLVY
DDKAFTIEEI KDAILNNFGF KDALEVGNYS MADQVKVDKT GKYDAIYKAC LDAPKYGNND
LYADNILKNY EVWLSKVCEE AQSLYAKKMY PCQISVSTHG PQGAATLATP DGRLSGTTYS
DGSVSAYAGT DKNGVYALFE SATIWDQAVV QNSQMNLKLH PTTIKGQQGT KKLLDLTRSY
LRKGGFHIQY NVVDSETLKD AQKNPDNYRQ LMVRVAGFTQ YWCELGKPIQ DEVIARTEYE
GV
