CBH_BIFLN
ID CBH_BIFLN Reviewed; 317 AA.
AC Q9KK62;
DT 17-JUN-2020, integrated into UniProtKB/Swiss-Prot.
DT 01-OCT-2000, sequence version 1.
DT 03-AUG-2022, entry version 81.
DE RecName: Full=Conjugated bile acid hydrolase {ECO:0000305|PubMed:10831430, ECO:0000305|PubMed:16905539};
DE EC=3.5.1.- {ECO:0000269|PubMed:10831430, ECO:0000269|PubMed:16905539};
DE AltName: Full=Bile salt hydrolase {ECO:0000303|PubMed:10831430};
DE Short=BSH {ECO:0000303|PubMed:10831430};
DE AltName: Full=Chenodeoxycholoyltaurine hydrolase {ECO:0000305|PubMed:10831430};
DE EC=3.5.1.74 {ECO:0000269|PubMed:10831430};
DE AltName: Full=Choloylglycine hydrolase {ECO:0000305|PubMed:10831430};
DE EC=3.5.1.24 {ECO:0000269|PubMed:10831430};
GN Name=bsh {ECO:0000303|PubMed:10831430, ECO:0000312|EMBL:AAF67801.1};
OS Bifidobacterium longum.
OC Bacteria; Actinobacteria; Bifidobacteriales; Bifidobacteriaceae;
OC Bifidobacterium.
OX NCBI_TaxID=216816;
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], PROTEIN SEQUENCE OF 2-31, FUNCTION,
RP CATALYTIC ACTIVITY, BIOPHYSICOCHEMICAL PROPERTIES, SUBSTRATE SPECIFICITY,
RP ACTIVITY REGULATION, SUBUNIT, MUTAGENESIS OF CYS-2, ACTIVE SITE, AND
RP INDUCTION.
RC STRAIN=SBT2928;
RX PubMed=10831430; DOI=10.1128/aem.66.6.2502-2512.2000;
RA Tanaka H., Hashiba H., Kok J., Mierau I.;
RT "Bile salt hydrolase of Bifidobacterium longum-biochemical and genetic
RT characterization.";
RL Appl. Environ. Microbiol. 66:2502-2512(2000).
RN [2] {ECO:0007744|PDB:2HEZ, ECO:0007744|PDB:2HF0}
RP X-RAY CRYSTALLOGRAPHY (2.30 ANGSTROMS) OF 2-317, FUNCTION, CATALYTIC
RP ACTIVITY, BIOPHYSICOCHEMICAL PROPERTIES, SUBSTRATE SPECIFICITY, ACTIVITY
RP REGULATION, ACTIVE SITE, SUBUNIT, AND MUTAGENESIS OF CYS-2 AND THR-3.
RX PubMed=16905539; DOI=10.1074/jbc.m604172200;
RA Kumar R.S., Brannigan J.A., Prabhune A.A., Pundle A.V., Dodson G.G.,
RA Dodson E.J., Suresh C.G.;
RT "Structural and functional analysis of a conjugated bile salt hydrolase
RT from Bifidobacterium longum reveals an evolutionary relationship with
RT penicillin V acylase.";
RL J. Biol. Chem. 281:32516-32525(2006).
CC -!- FUNCTION: Bile salt hydrolase that catalyzes the deconjugation of
CC glycine- and taurine-linked bile salts, which occurs naturally in the
CC intestines of humans, releasing amino acid residues and deconjugated
CC bile salts (bile acids). Can hydrolyze the amid bond in all six major
CC human bile salts, namely glycocholate (GCA), glycodeoxycholate (GDCA),
CC glycochenodeoxycholate (GCDCA), taurocholate (TCA), taurodeoxycholate
CC (TDCA) and taurochenodeoxycholate (TCDCA). Shows a slight preference
CC for glycine-conjugated bile acids as substrates (PubMed:10831430,
CC PubMed:16905539). Is totally inactive toward penicillin V
CC (PubMed:16905539). {ECO:0000269|PubMed:10831430,
CC ECO:0000269|PubMed:16905539}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=glycocholate + H2O = cholate + glycine; Xref=Rhea:RHEA:19353,
CC ChEBI:CHEBI:15377, ChEBI:CHEBI:29746, ChEBI:CHEBI:29747,
CC ChEBI:CHEBI:57305; EC=3.5.1.24;
CC Evidence={ECO:0000269|PubMed:10831430, ECO:0000269|PubMed:16905539};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:19354;
CC Evidence={ECO:0000305|PubMed:10831430};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=glycodeoxycholate + H2O = deoxycholate + glycine;
CC Xref=Rhea:RHEA:47552, ChEBI:CHEBI:15377, ChEBI:CHEBI:23614,
CC ChEBI:CHEBI:57305, ChEBI:CHEBI:82982;
CC Evidence={ECO:0000269|PubMed:10831430, ECO:0000269|PubMed:16905539};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:47553;
CC Evidence={ECO:0000305|PubMed:10831430};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=chenodeoxycholate + glycine = glycochenodeoxycholate + H2O;
CC Xref=Rhea:RHEA:47112, ChEBI:CHEBI:15377, ChEBI:CHEBI:36234,
CC ChEBI:CHEBI:36252, ChEBI:CHEBI:57305;
CC Evidence={ECO:0000269|PubMed:10831430, ECO:0000269|PubMed:16905539};
CC PhysiologicalDirection=right-to-left; Xref=Rhea:RHEA:47114;
CC Evidence={ECO:0000305|PubMed:10831430};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=cholate + taurine = H2O + taurocholate; Xref=Rhea:RHEA:47108,
CC ChEBI:CHEBI:15377, ChEBI:CHEBI:29747, ChEBI:CHEBI:36257,
CC ChEBI:CHEBI:507393; Evidence={ECO:0000269|PubMed:10831430,
CC ECO:0000269|PubMed:16905539};
CC PhysiologicalDirection=right-to-left; Xref=Rhea:RHEA:47110;
CC Evidence={ECO:0000305|PubMed:10831430};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=H2O + taurodeoxycholate = deoxycholate + taurine;
CC Xref=Rhea:RHEA:47556, ChEBI:CHEBI:15377, ChEBI:CHEBI:23614,
CC ChEBI:CHEBI:36261, ChEBI:CHEBI:507393;
CC Evidence={ECO:0000269|PubMed:10831430, ECO:0000269|PubMed:16905539};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:47557;
CC Evidence={ECO:0000305|PubMed:10831430};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=H2O + taurochenodeoxycholate = chenodeoxycholate + taurine;
CC Xref=Rhea:RHEA:16309, ChEBI:CHEBI:9407, ChEBI:CHEBI:15377,
CC ChEBI:CHEBI:36234, ChEBI:CHEBI:507393; EC=3.5.1.74;
CC Evidence={ECO:0000269|PubMed:10831430, ECO:0000269|PubMed:16905539};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:16310;
CC Evidence={ECO:0000305|PubMed:10831430};
CC -!- ACTIVITY REGULATION: Competitively inhibited by the products cholate
CC (CA) and deoxycholate (DCA), and by phenylacetate and 4-
CC aminophenylacetate. Penicillin V and penicillin G show mixed inhibition
CC (PubMed:16905539). Strongly inhibited by thiol enzyme inhibitors in
CC vitro (PubMed:10831430). {ECO:0000269|PubMed:10831430,
CC ECO:0000269|PubMed:16905539}.
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=0.16 mM for glycocholate (at 37 degrees Celsius and pH 5.5)
CC {ECO:0000269|PubMed:10831430};
CC KM=0.28 mM for glycodeoxycholate (at 37 degrees Celsius and pH 5.5)
CC {ECO:0000269|PubMed:10831430};
CC KM=0.13 mM for glycochenodeoxycholate (at 37 degrees Celsius and pH
CC 5.5) {ECO:0000269|PubMed:10831430};
CC KM=1.12 mM for taurocholate (at 37 degrees Celsius and pH 5.5)
CC {ECO:0000269|PubMed:10831430};
CC KM=0.79 mM for taurodeoxycholate (at 37 degrees Celsius and pH 5.5)
CC {ECO:0000269|PubMed:10831430};
CC KM=0.33 mM for taurochenodeoxycholate (at 37 degrees Celsius and pH
CC 5.5) {ECO:0000269|PubMed:10831430};
CC KM=0.22 mM for glycocholate (at 40 degrees Celsius and pH 6.5)
CC {ECO:0000269|PubMed:16905539};
CC KM=0.18 mM for glycodeoxycholate (at 40 degrees Celsius and pH 6.5)
CC {ECO:0000269|PubMed:16905539};
CC KM=0.28 mM for glycochenodeoxycholate (at 40 degrees Celsius and pH
CC 6.5) {ECO:0000269|PubMed:16905539};
CC KM=0.32 mM for taurocholate (at 40 degrees Celsius and pH 6.5)
CC {ECO:0000269|PubMed:16905539};
CC KM=0.49 mM for taurodeoxycholate (at 40 degrees Celsius and pH 6.5)
CC {ECO:0000269|PubMed:16905539};
CC KM=0.42 mM for taurochenodeoxycholate (at 40 degrees Celsius and pH
CC 6.5) {ECO:0000269|PubMed:16905539};
CC Note=kcat is 85 sec(-1) with glycocholate as substrate. kcat is 76
CC sec(-1) with taurocholate as substrate (at 40 degrees Celsius and pH
CC 6.5). {ECO:0000269|PubMed:16905539};
CC pH dependence:
CC Optimum pH is 6. Highly active in the pH range 5-7. Is stable at pH
CC values from 4 to 8. At pH values above 8 and below 4 the enzyme is
CC rapidly inactivated. {ECO:0000269|PubMed:10831430};
CC Temperature dependence:
CC Optimum temperature is 40-45 degrees Celsius. Is stable at
CC temperatures from 4 to 37 degrees Celsius. During 30 minutes of
CC incubation at 40 degrees Celsius, about 20 to 30% of the activity is
CC lost, and at 50 degrees Celsius only 20% of the activity is retained.
CC {ECO:0000269|PubMed:10831430};
CC -!- PATHWAY: Lipid metabolism; bile acid biosynthesis.
CC {ECO:0000305|PubMed:10831430}.
CC -!- SUBUNIT: Homotetramer (PubMed:10831430, PubMed:16905539). The tetramer
CC consists of a dimer of dimers (PubMed:16905539).
CC {ECO:0000269|PubMed:10831430, ECO:0000269|PubMed:16905539}.
CC -!- INDUCTION: Is part of an operon containing at least two genes, bsh and
CC glnE (GlnE is glutamine synthetase adenylyltransferase).
CC {ECO:0000269|PubMed:10831430}.
CC -!- SIMILARITY: Belongs to the peptidase C59 family. {ECO:0000305}.
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DR EMBL; AF148138; AAF67801.1; -; Genomic_DNA.
DR RefSeq; WP_013410903.1; NZ_SPGO01000023.1.
DR PDB; 2HEZ; X-ray; 2.50 A; A/B=2-317.
DR PDB; 2HF0; X-ray; 2.30 A; A/B=2-317.
DR PDBsum; 2HEZ; -.
DR PDBsum; 2HF0; -.
DR AlphaFoldDB; Q9KK62; -.
DR SMR; Q9KK62; -.
DR SwissLipids; SLP:000001350; -.
DR MEROPS; C59.951; -.
DR MoonProt; Q9KK62; -.
DR GeneID; 66505150; -.
DR OMA; MCTRLVY; -.
DR BioCyc; MetaCyc:MON-15684; -.
DR BRENDA; 3.5.1.24; 851.
DR UniPathway; UPA00221; -.
DR EvolutionaryTrace; Q9KK62; -.
DR GO; GO:0009274; C:peptidoglycan-based cell wall; IDA:CAFA.
DR GO; GO:0047742; F:chenodeoxycholoyltaurine hydrolase activity; IEA:UniProtKB-EC.
DR GO; GO:0045302; F:choloylglycine hydrolase activity; IDA:CAFA.
DR GO; GO:0006699; P:bile acid biosynthetic process; IEA:UniProtKB-UniPathway.
DR InterPro; IPR029132; CBAH/NAAA_C.
DR InterPro; IPR029055; Ntn_hydrolases_N.
DR Pfam; PF02275; CBAH; 1.
DR SUPFAM; SSF56235; SSF56235; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Direct protein sequencing; Hydrolase; Lipid metabolism.
FT INIT_MET 1
FT /note="Removed"
FT /evidence="ECO:0000269|PubMed:10831430"
FT CHAIN 2..317
FT /note="Conjugated bile acid hydrolase"
FT /id="PRO_0000450324"
FT ACT_SITE 2
FT /note="Nucleophile"
FT /evidence="ECO:0000305|PubMed:10831430"
FT BINDING 2
FT /ligand="deoxycholate"
FT /ligand_id="ChEBI:CHEBI:23614"
FT /evidence="ECO:0000250|UniProtKB:P54965"
FT BINDING 18
FT /ligand="deoxycholate"
FT /ligand_id="ChEBI:CHEBI:23614"
FT /evidence="ECO:0000250|UniProtKB:P54965"
FT BINDING 82
FT /ligand="taurine"
FT /ligand_id="ChEBI:CHEBI:507393"
FT /evidence="ECO:0000250|UniProtKB:P54965"
FT MUTAGEN 2
FT /note="C->A: Loss of catalytic activity."
FT /evidence="ECO:0000269|PubMed:10831430,
FT ECO:0000269|PubMed:16905539"
FT MUTAGEN 3
FT /note="T->A: About 2-fold decrease in catalytic activity,
FT but no change in substrate affinity."
FT /evidence="ECO:0000269|PubMed:16905539"
FT STRAND 3..8
FT /evidence="ECO:0007829|PDB:2HF0"
FT STRAND 14..23
FT /evidence="ECO:0007829|PDB:2HF0"
FT STRAND 29..33
FT /evidence="ECO:0007829|PDB:2HF0"
FT STRAND 54..72
FT /evidence="ECO:0007829|PDB:2HF0"
FT STRAND 77..82
FT /evidence="ECO:0007829|PDB:2HF0"
FT TURN 84..86
FT /evidence="ECO:0007829|PDB:2HF0"
FT STRAND 90..92
FT /evidence="ECO:0007829|PDB:2HF0"
FT STRAND 97..101
FT /evidence="ECO:0007829|PDB:2HF0"
FT TURN 102..104
FT /evidence="ECO:0007829|PDB:2HF0"
FT HELIX 105..112
FT /evidence="ECO:0007829|PDB:2HF0"
FT HELIX 116..123
FT /evidence="ECO:0007829|PDB:2HF0"
FT STRAND 126..129
FT /evidence="ECO:0007829|PDB:2HF0"
FT STRAND 134..136
FT /evidence="ECO:0007829|PDB:2HF0"
FT STRAND 141..146
FT /evidence="ECO:0007829|PDB:2HF0"
FT STRAND 151..157
FT /evidence="ECO:0007829|PDB:2HF0"
FT STRAND 160..165
FT /evidence="ECO:0007829|PDB:2HF0"
FT STRAND 173..175
FT /evidence="ECO:0007829|PDB:2HF0"
FT HELIX 177..183
FT /evidence="ECO:0007829|PDB:2HF0"
FT HELIX 184..187
FT /evidence="ECO:0007829|PDB:2HF0"
FT STRAND 198..200
FT /evidence="ECO:0007829|PDB:2HF0"
FT STRAND 203..205
FT /evidence="ECO:0007829|PDB:2HF0"
FT HELIX 212..214
FT /evidence="ECO:0007829|PDB:2HF0"
FT HELIX 223..236
FT /evidence="ECO:0007829|PDB:2HF0"
FT HELIX 243..253
FT /evidence="ECO:0007829|PDB:2HF0"
FT TURN 254..257
FT /evidence="ECO:0007829|PDB:2HF0"
FT STRAND 273..281
FT /evidence="ECO:0007829|PDB:2HF0"
FT TURN 282..285
FT /evidence="ECO:0007829|PDB:2HF0"
FT STRAND 286..293
FT /evidence="ECO:0007829|PDB:2HF0"
FT STRAND 298..302
FT /evidence="ECO:0007829|PDB:2HF0"
FT STRAND 309..311
FT /evidence="ECO:0007829|PDB:2HF0"
FT STRAND 313..315
FT /evidence="ECO:0007829|PDB:2HF0"
SQ SEQUENCE 317 AA; 35155 MW; 178B263FBBA205CC CRC64;
MCTGVRFSDD EGNTYFGRNL DWSFSYGETI LVTPRGYHYD TVFGAGGKAK PNAVIGVGVV
MADRPMYFDC ANEHGLAIAG LNFPGYASFV HEPVEGTENV ATFEFPLWVA RNFDSVDEVE
ETLRNVTLVS QIVPGQQESL LHWFIGDGKR SIVVEQMADG MHVHHDDVDV LTNQPTFDFH
MENLRNYMCV SNEMAEPTSW GKASLTAWGA GVGMHGIPGD VSSPSRFVRV AYTNAHYPQQ
NDEAANVSRL FHTLGSVQMV DGMAKMGDGQ FERTLFTSGY SSKTNTYYMN TYDDPAIRSY
AMADYDMDSS ELISVAR
