HPBD_PARDP
ID HPBD_PARDP Reviewed; 369 AA.
AC A1B198;
DT 19-FEB-2014, integrated into UniProtKB/Swiss-Prot.
DT 23-JAN-2007, sequence version 1.
DT 03-AUG-2022, entry version 90.
DE RecName: Full=4-hydroxyproline betaine 2-epimerase;
DE Short=Hyp-B 2-epimerase;
DE EC=5.1.1.22 {ECO:0000269|PubMed:24056934, ECO:0000269|PubMed:24520058};
DE AltName: Full=(4R)-4-hydroxyproline betaine 2-epimerase;
GN Name=hpbD; OrderedLocusNames=Pden_1187;
OS Paracoccus denitrificans (strain Pd 1222).
OC Bacteria; Proteobacteria; Alphaproteobacteria; Rhodobacterales;
OC Rhodobacteraceae; Paracoccus.
OX NCBI_TaxID=318586;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=Pd 1222;
RA Copeland A., Lucas S., Lapidus A., Barry K., Detter J.C.,
RA Glavina del Rio T., Hammon N., Israni S., Dalin E., Tice H., Pitluck S.,
RA Munk A.C., Brettin T., Bruce D., Han C., Tapia R., Gilna P., Schmutz J.,
RA Larimer F., Land M., Hauser L., Kyrpides N., Lykidis A., Spiro S.,
RA Richardson D.J., Moir J.W.B., Ferguson S.J., van Spanning R.J.M.,
RA Richardson P.;
RT "Complete sequence of chromosome 1 of Paracoccus denitrificans PD1222.";
RL Submitted (DEC-2006) to the EMBL/GenBank/DDBJ databases.
RN [2]
RP FUNCTION, CATALYTIC ACTIVITY, KINETIC PARAMETERS, GENE NAME, INDUCTION,
RP DISRUPTION PHENOTYPE, AND PATHWAY.
RC STRAIN=Pd 1222;
RX PubMed=24056934; DOI=10.1038/nature12576;
RA Zhao S., Kumar R., Sakai A., Vetting M.W., Wood B.M., Brown S.,
RA Bonanno J.B., Hillerich B.S., Seidel R.D., Babbitt P.C., Almo S.C.,
RA Sweedler J.V., Gerlt J.A., Cronan J.E., Jacobson M.P.;
RT "Discovery of new enzymes and metabolic pathways by using structure and
RT genome context.";
RL Nature 502:698-702(2013).
RN [3]
RP X-RAY CRYSTALLOGRAPHY (1.60 ANGSTROMS) IN COMPLEXES WITH MAGNESIUM AND
RP HYDROXYPROLINE BETAINE OR PROLINE BETAINE, COFACTOR, CATALYTIC ACTIVITY,
RP AND BIOPHYSICOCHEMICAL PROPERTIES.
RX PubMed=24520058; DOI=10.1128/mbio.00933-13;
RA Kumar R., Zhao S., Vetting M.W., Wood B.M., Sakai A., Cho K., Solbiati J.,
RA Almo S.C., Sweedler J.V., Jacobson M.P., Gerlt J.A., Cronan J.E.;
RT "Prediction and biochemical demonstration of a catabolic pathway for the
RT osmoprotectant proline betaine.";
RL MBio 5:E00933-E00933(2014).
CC -!- FUNCTION: Catalyzes the 2-epimerization of trans-4-hydroxy-L-proline
CC betaine (tHyp-B) to cis-4-hydroxy-D-proline betaine (cHyp-B). Is
CC involved in a catabolic pathway that degrades tHyp-B to alpha-
CC ketoglutarate. This pathway would permit the utilization of tHyp-B as a
CC carbon and nitrogen source in the absence of osmotic stress, since
CC tHyp-B functions as an osmolyte and is not catabolized when it is
CC needed as osmoprotectant. Can also catalyze the racemization of L-
CC proline betaine. {ECO:0000269|PubMed:24056934}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=trans-4-hydroxy-L-proline betaine = cis-4-hydroxy-D-proline
CC betaine; Xref=Rhea:RHEA:47544, ChEBI:CHEBI:85533, ChEBI:CHEBI:85534;
CC EC=5.1.1.22; Evidence={ECO:0000269|PubMed:24056934,
CC ECO:0000269|PubMed:24520058};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=L-proline betaine = D-proline betaine; Xref=Rhea:RHEA:51884,
CC ChEBI:CHEBI:35280, ChEBI:CHEBI:134398; EC=5.1.1.22;
CC Evidence={ECO:0000269|PubMed:24056934, ECO:0000269|PubMed:24520058};
CC -!- COFACTOR:
CC Name=Mg(2+); Xref=ChEBI:CHEBI:18420;
CC Evidence={ECO:0000269|PubMed:24520058};
CC Note=Binds 1 Mg(2+) ion per subunit. {ECO:0000269|PubMed:24520058};
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=64 mM for trans-4-hydroxy-L-proline betaine
CC {ECO:0000269|PubMed:24056934};
CC KM=34 mM for L-proline betaine {ECO:0000269|PubMed:24056934};
CC KM=7.3 mM for D-proline betaine {ECO:0000269|PubMed:24520058};
CC Note=kcat is 110 sec(-1) with trans-4-hydroxy-L-proline betaine as
CC substrate (PubMed:24056934). kcat is 68 sec(-1) with L-proline
CC betaine as substrate (PubMed:24056934). kcat is 28 sec(-1) with D-
CC proline betaine as substrate (PubMed:24520058).
CC {ECO:0000269|PubMed:24056934, ECO:0000269|PubMed:24520058};
CC -!- INDUCTION: Up-regulated by tHyp-B and cHyp-B. Repressed by high salt
CC concentration. {ECO:0000269|PubMed:24056934}.
CC -!- DISRUPTION PHENOTYPE: Cells lacking this gene grow more slowly than
CC wild-type on tHyp-B as sole carbon source, whereas growth is normal on
CC cHyp-B. When both hpbD and hypF are disrupted, P.denitrificans is
CC unable to utilize tHyp-B or tHyp as sole carbon source.
CC {ECO:0000269|PubMed:24056934}.
CC -!- SIMILARITY: Belongs to the mandelate racemase/muconate lactonizing
CC enzyme family. {ECO:0000305}.
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DR EMBL; CP000489; ABL69292.1; -; Genomic_DNA.
DR RefSeq; WP_011747512.1; NC_008686.1.
DR PDB; 4E8G; X-ray; 2.00 A; A/B=2-369.
DR PDB; 4IZG; X-ray; 1.70 A; A/B=1-369.
DR PDB; 4J1O; X-ray; 1.60 A; A/B=1-369.
DR PDBsum; 4E8G; -.
DR PDBsum; 4IZG; -.
DR PDBsum; 4J1O; -.
DR AlphaFoldDB; A1B198; -.
DR SMR; A1B198; -.
DR STRING; 318586.Pden_1187; -.
DR PRIDE; A1B198; -.
DR EnsemblBacteria; ABL69292; ABL69292; Pden_1187.
DR KEGG; pde:Pden_1187; -.
DR eggNOG; COG4948; Bacteria.
DR HOGENOM; CLU_030273_4_5_5; -.
DR OMA; PLCTNMC; -.
DR BioCyc; MetaCyc:MON-18941; -.
DR BRENDA; 5.1.1.22; 3341.
DR Proteomes; UP000000361; Chromosome 1.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0036361; F:racemase activity, acting on amino acids and derivatives; IDA:UniProtKB.
DR GO; GO:0016855; F:racemase and epimerase activity, acting on amino acids and derivatives; IDA:CACAO.
DR GO; GO:0006579; P:amino-acid betaine catabolic process; IMP:UniProtKB.
DR Gene3D; 3.20.20.120; -; 1.
DR Gene3D; 3.30.390.10; -; 1.
DR InterPro; IPR034622; 4R-hPro_betaine_2-epimerase.
DR InterPro; IPR036849; Enolase-like_C_sf.
DR InterPro; IPR029017; Enolase-like_N.
DR InterPro; IPR029065; Enolase_C-like.
DR InterPro; IPR013342; Mandelate_racemase_C.
DR InterPro; IPR013341; Mandelate_racemase_N_dom.
DR Pfam; PF13378; MR_MLE_C; 1.
DR Pfam; PF02746; MR_MLE_N; 1.
DR SFLD; SFLDF00556; 4R-hydroxyproline_betaine_2-ep; 1.
DR SMART; SM00922; MR_MLE; 1.
DR SUPFAM; SSF51604; SSF51604; 1.
DR SUPFAM; SSF54826; SSF54826; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Isomerase; Magnesium; Metal-binding; Reference proteome.
FT CHAIN 1..369
FT /note="4-hydroxyproline betaine 2-epimerase"
FT /id="PRO_0000425279"
FT ACT_SITE 164
FT /note="Proton donor/acceptor"
FT /evidence="ECO:0000250"
FT ACT_SITE 266
FT /note="Proton donor/acceptor"
FT /evidence="ECO:0000250"
FT BINDING 56
FT /ligand="substrate"
FT BINDING 162
FT /ligand="substrate"
FT BINDING 194
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT BINDING 219
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT BINDING 242
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT BINDING 295
FT /ligand="substrate"
FT STRAND 3..14
FT /evidence="ECO:0007829|PDB:4J1O"
FT STRAND 20..22
FT /evidence="ECO:0007829|PDB:4J1O"
FT STRAND 25..39
FT /evidence="ECO:0007829|PDB:4J1O"
FT STRAND 44..49
FT /evidence="ECO:0007829|PDB:4J1O"
FT STRAND 56..58
FT /evidence="ECO:0007829|PDB:4J1O"
FT HELIX 61..71
FT /evidence="ECO:0007829|PDB:4J1O"
FT HELIX 72..75
FT /evidence="ECO:0007829|PDB:4J1O"
FT HELIX 83..91
FT /evidence="ECO:0007829|PDB:4J1O"
FT HELIX 98..116
FT /evidence="ECO:0007829|PDB:4J1O"
FT HELIX 120..123
FT /evidence="ECO:0007829|PDB:4J1O"
FT STRAND 130..133
FT /evidence="ECO:0007829|PDB:4J1O"
FT STRAND 136..138
FT /evidence="ECO:0007829|PDB:4J1O"
FT HELIX 143..156
FT /evidence="ECO:0007829|PDB:4J1O"
FT STRAND 159..164
FT /evidence="ECO:0007829|PDB:4J1O"
FT HELIX 170..184
FT /evidence="ECO:0007829|PDB:4J1O"
FT TURN 185..188
FT /evidence="ECO:0007829|PDB:4J1O"
FT STRAND 190..194
FT /evidence="ECO:0007829|PDB:4J1O"
FT HELIX 201..210
FT /evidence="ECO:0007829|PDB:4J1O"
FT STRAND 216..220
FT /evidence="ECO:0007829|PDB:4J1O"
FT STRAND 222..224
FT /evidence="ECO:0007829|PDB:4J1O"
FT HELIX 225..231
FT /evidence="ECO:0007829|PDB:4J1O"
FT HELIX 232..234
FT /evidence="ECO:0007829|PDB:4J1O"
FT STRAND 239..242
FT /evidence="ECO:0007829|PDB:4J1O"
FT HELIX 248..256
FT /evidence="ECO:0007829|PDB:4J1O"
FT STRAND 261..266
FT /evidence="ECO:0007829|PDB:4J1O"
FT HELIX 267..270
FT /evidence="ECO:0007829|PDB:4J1O"
FT HELIX 273..285
FT /evidence="ECO:0007829|PDB:4J1O"
FT STRAND 290..293
FT /evidence="ECO:0007829|PDB:4J1O"
FT HELIX 299..309
FT /evidence="ECO:0007829|PDB:4J1O"
FT HELIX 314..316
FT /evidence="ECO:0007829|PDB:4J1O"
FT STRAND 317..319
FT /evidence="ECO:0007829|PDB:4J1O"
FT HELIX 324..326
FT /evidence="ECO:0007829|PDB:4J1O"
FT TURN 333..335
FT /evidence="ECO:0007829|PDB:4J1O"
FT STRAND 343..345
FT /evidence="ECO:0007829|PDB:4J1O"
FT STRAND 349..351
FT /evidence="ECO:0007829|PDB:4J1O"
FT HELIX 358..360
FT /evidence="ECO:0007829|PDB:4J1O"
FT STRAND 365..368
FT /evidence="ECO:0007829|PDB:4J1O"
SQ SEQUENCE 369 AA; 39382 MW; 31E3E18DBDF60A5A CRC64;
MKIAEIHVYA HDLPVKDGPY TIASSTVWSL QTTLVKIVAD SGLAGWGETC PVGPTYAPSH
ALGARAALAE MAPGLIGANP LQPLVLRRRM DGLLCGHNYA KAAIDIAAYD LMGKHYGVRV
ADLLGGVAAE RVPSYYATGI GQPDEIARIA AEKVAEGFPR LQIKIGGRPV EIDIETVRKV
WERIRGTGTR LAVDGNRSLP SRDALRLSRE CPEIPFVLEQ PCNTLEEIAA IRGRVQHGIY
LDESGEDLST VIRAAGQGLC DGFGMKLTRI GGLQQMAAFR DICEARALPH SCDDAWGGDI
IAAACTHIGA TVQPRLNEGV WVAQPYIAQP YDEENGIRIA GGHIDLPKGP GLGITPDESL
FGPPVASFS
