ID   4HYPE_BRUSU             Reviewed;         333 AA.
AC   Q8FYS0; A8DEY2; G0K7C9;
DT   25-NOV-2008, integrated into UniProtKB/Swiss-Prot.
DT   01-MAR-2003, sequence version 1.
DT   27-MAR-2024, entry version 91.
DE   RecName: Full=4-hydroxyproline 2-epimerase {ECO:0000303|PubMed:24980702};
DE            Short=4Hyp 2-epimerase;
DE            Short=4HypE {ECO:0000303|PubMed:24980702};
DE            EC=5.1.1.8 {ECO:0000269|PubMed:17849014, ECO:0000269|PubMed:24980702};
DE   AltName: Full=Hydroxyproline-2-epimerase {ECO:0000303|PubMed:17849014};
DE            Short=BsHyPRE {ECO:0000303|PubMed:17849014};
GN   OrderedLocusNames=BR1792, BS1330_I1786;
OS   Brucella suis biovar 1 (strain 1330).
OC   Bacteria; Pseudomonadota; Alphaproteobacteria; Hyphomicrobiales;
OC   Brucellaceae; Brucella/Ochrobactrum group; Brucella.
OX   NCBI_TaxID=204722;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [GENOMIC DNA], FUNCTION, CATALYTIC ACTIVITY, ACTIVITY
RP   REGULATION, AND BIOPHYSICOCHEMICAL PROPERTIES.
RC   STRAIN=1330;
RX   PubMed=17849014; DOI=10.1371/journal.pone.0000885;
RA   Goytia M., Chamond N., Cosson A., Coatnoan N., Hermant D., Berneman A.,
RA   Minoprio P.;
RT   "Molecular and structural discrimination of proline racemase and
RT   hydroxyproline-2-epimerase from nosocomial and bacterial pathogens.";
RL   PLoS ONE 2:E885-E885(2007).
RN   [2]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC   STRAIN=1330;
RX   PubMed=12271122; DOI=10.1073/pnas.192319099;
RA   Paulsen I.T., Seshadri R., Nelson K.E., Eisen J.A., Heidelberg J.F.,
RA   Read T.D., Dodson R.J., Umayam L.A., Brinkac L.M., Beanan M.J.,
RA   Daugherty S.C., DeBoy R.T., Durkin A.S., Kolonay J.F., Madupu R.,
RA   Nelson W.C., Ayodeji B., Kraul M., Shetty J., Malek J.A., Van Aken S.E.,
RA   Riedmuller S., Tettelin H., Gill S.R., White O., Salzberg S.L.,
RA   Hoover D.L., Lindler L.E., Halling S.M., Boyle S.M., Fraser C.M.;
RT   "The Brucella suis genome reveals fundamental similarities between animal
RT   and plant pathogens and symbionts.";
RL   Proc. Natl. Acad. Sci. U.S.A. 99:13148-13153(2002).
RN   [3]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC   STRAIN=1330;
RX   PubMed=22038969; DOI=10.1128/jb.06181-11;
RA   Tae H., Shallom S., Settlage R., Preston D., Adams L.G., Garner H.R.;
RT   "Revised genome sequence of Brucella suis 1330.";
RL   J. Bacteriol. 193:6410-6410(2011).
RN   [4]
RP   FUNCTION, AND CATALYTIC ACTIVITY.
RX   PubMed=24980702; DOI=10.7554/elife.03275;
RA   Zhao S., Sakai A., Zhang X., Vetting M.W., Kumar R., Hillerich B.,
RA   San Francisco B., Solbiati J., Steves A., Brown S., Akiva E., Barber A.,
RA   Seidel R.D., Babbitt P.C., Almo S.C., Gerlt J.A., Jacobson M.P.;
RT   "Prediction and characterization of enzymatic activities guided by sequence
RT   similarity and genome neighborhood networks.";
RL   Elife 3:E03275-E03275(2014).
CC   -!- FUNCTION: Allows intracellular utilization of 4-hydroxyproline, one of
CC       the major constituents of host collagen, by converting trans-4-hydroxy-
CC       L-proline (t4LHyp) to cis-4-hydroxy-D-proline (c4DHyp), which can be
CC       further metabolized by intracellular 4-hydroxy-D-proline oxidases.
CC       Strong B-cell mitogen. Plays an important role in the regulation of
CC       intra- and extracellular amino acid pools, allowing the bacterium to
CC       profit from host precursors and enzymatic pathways. Displays no proline
CC       racemase activity. {ECO:0000269|PubMed:17849014,
CC       ECO:0000269|PubMed:24980702}.
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=trans-4-hydroxy-L-proline = cis-4-hydroxy-D-proline;
CC         Xref=Rhea:RHEA:21152, ChEBI:CHEBI:57690, ChEBI:CHEBI:58375;
CC         EC=5.1.1.8; Evidence={ECO:0000269|PubMed:17849014,
CC         ECO:0000269|PubMed:24980702};
CC   -!- ACTIVITY REGULATION: Inhibited by iodoacetate, iodoacetamide and by
CC       high amounts (10 mM) of pyrrole-2-carboxylic acid (PYC). Not inhibited
CC       by PYC at 1 mM. {ECO:0000269|PubMed:17849014}.
CC   -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC       Kinetic parameters:
CC         KM=7.6 mM for 4-hydroxy-L-proline {ECO:0000269|PubMed:17849014};
CC         KM=10.8 mM for 4-hydroxy-D-proline {ECO:0000269|PubMed:17849014};
CC         Vmax=0.5 uM/sec/mg enzyme with 4-hydroxy-L-proline as substrate (at
CC         37 degrees Celsius) {ECO:0000269|PubMed:17849014};
CC         Vmax=0.75 uM/sec/mg enzyme with 4-hydroxy-D-proline as substrate (at
CC         37 degrees Celsius) {ECO:0000269|PubMed:17849014};
CC   -!- SUBUNIT: Homodimer. {ECO:0000250}.
CC   -!- MISCELLANEOUS: This enzyme does not require pyridoxal phosphate (PLP)
CC       as a cofactor.
CC   -!- SIMILARITY: Belongs to the proline racemase family. {ECO:0000305}.
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DR   EMBL; EF495343; ABS82395.1; -; Genomic_DNA.
DR   EMBL; AE014291; AAN30688.1; -; Genomic_DNA.
DR   EMBL; CP002997; AEM19105.1; -; Genomic_DNA.
DR   RefSeq; WP_004690494.1; NZ_KN046804.1.
DR   AlphaFoldDB; Q8FYS0; -.
DR   SMR; Q8FYS0; -.
DR   GeneID; 58775217; -.
DR   KEGG; bms:BR1792; -.
DR   KEGG; bsi:BS1330_I1786; -.
DR   PATRIC; fig|204722.22.peg.66; -.
DR   HOGENOM; CLU_036729_0_0_5; -.
DR   PhylomeDB; Q8FYS0; -.
DR   BRENDA; 5.1.1.8; 8693.
DR   Proteomes; UP000007104; Chromosome I.
DR   GO; GO:0047580; F:4-hydroxyproline epimerase activity; IEA:UniProtKB-EC.
DR   InterPro; IPR008794; Pro_racemase_fam.
DR   PANTHER; PTHR33442; TRANS-3-HYDROXY-L-PROLINE DEHYDRATASE; 1.
DR   PANTHER; PTHR33442:SF5; TRANS-3-HYDROXY-L-PROLINE DEHYDRATASE-RELATED; 1.
DR   Pfam; PF05544; Pro_racemase; 1.
DR   PIRSF; PIRSF029792; Pro_racemase; 1.
DR   SFLD; SFLDS00028; Proline_Racemase; 1.
DR   SUPFAM; SSF54506; Diaminopimelate epimerase-like; 1.
PE   1: Evidence at protein level;
KW   Isomerase.
FT   CHAIN           1..333
FT                   /note="4-hydroxyproline 2-epimerase"
FT                   /id="PRO_0000354032"
FT   ACT_SITE        90
FT                   /note="Proton acceptor"
FT                   /evidence="ECO:0000250|UniProtKB:Q4KGU2"
FT   ACT_SITE        253
FT                   /note="Proton donor"
FT                   /evidence="ECO:0000250|UniProtKB:Q4KGU2"
FT   BINDING         91..92
FT                   /ligand="substrate"
FT                   /evidence="ECO:0000250|UniProtKB:Q4KGU2"
FT   BINDING         223
FT                   /ligand="substrate"
FT                   /evidence="ECO:0000250|UniProtKB:Q4KGU2"
FT   BINDING         249
FT                   /ligand="substrate"
FT                   /evidence="ECO:0000250|UniProtKB:Q4KGU2"
FT   BINDING         254..255
FT                   /ligand="substrate"
FT                   /evidence="ECO:0000250|UniProtKB:Q4KGU2"
SQ   SEQUENCE   333 AA;  36592 MW;  320E7AA563495FBD CRC64;
     MARHSFFCVD GHTCGNPVRL VAGGGPNLNG STMMEKRAHF LAEYDWIRTG LMFEPRGHDM
     MSGSILYPPT RPDCDVAVLF IETSGCLPMC GHGTIGTVTM AIEQGLVTPK TPGKLNLDTP
     AGLVAIEYEQ DGQYVERVRL TNVPAFLYAE GLEVECPDLG PIKVDVAYGG NFYAIVEPQE
     NYTDMDDYSA LQLIAWSPVL RQRLNEKYKF QHPELPDINR LSHILWTGKP KHPQAHARNA
     VFYGDKAIDR SPCGTGTSAR MAQLAAKGKL KPGDEFIHES IIGSLFHGRV ERAAEVAGRP
     AIVPSIAGWA RMTGYNTIFI DDRDPFAHGF SVA
//