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 27-MAR-2024, entry version 96. 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; Pseudomonadota; Alphaproteobacteria; Rhodobacterales; OC Paracoccaceae; 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 CC D-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}. CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- 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 EnsemblBacteria; ABL69292; ABL69292; Pden_1187. DR GeneID; 75500708; -. DR KEGG; pde:Pden_1187; -. DR eggNOG; COG4948; Bacteria. DR HOGENOM; CLU_030273_4_5_5; -. DR OrthoDB; 9802699at2; -. DR BioCyc; MetaCyc:MONOMER-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 CDD; cd00308; enolase_like; 1. DR Gene3D; 3.20.20.120; Enolase-like C-terminal domain; 1. DR Gene3D; 3.30.390.10; Enolase-like, N-terminal domain; 1. DR InterPro; IPR034622; 4R-hPro_betaine_2-epimerase. DR InterPro; IPR034593; DgoD-like. 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 PANTHER; PTHR48080; D-GALACTONATE DEHYDRATASE-RELATED; 1. DR PANTHER; PTHR48080:SF3; ENOLASE SUPERFAMILY MEMBER DDB_G0284701; 1. DR Pfam; PF13378; MR_MLE_C; 1. DR Pfam; PF02746; MR_MLE_N; 1. DR SFLD; SFLDF00556; 4R-hydroxyproline_betaine_2-ep; 1. DR SFLD; SFLDS00001; Enolase; 1. DR SMART; SM00922; MR_MLE; 1. DR SUPFAM; SSF51604; Enolase C-terminal domain-like; 1. DR SUPFAM; SSF54826; Enolase N-terminal domain-like; 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 //