4HYPE_PSEAE
ID 4HYPE_PSEAE Reviewed; 314 AA.
AC Q9I476; A8DEX0;
DT 25-NOV-2008, integrated into UniProtKB/Swiss-Prot.
DT 01-MAR-2001, sequence version 1.
DT 03-AUG-2022, entry version 105.
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:20665524, ECO:0000269|PubMed:24980702};
DE AltName: Full=Hydroxyproline-2-epimerase {ECO:0000303|PubMed:17849014};
DE Short=PaHyPRE {ECO:0000303|PubMed:17849014};
GN OrderedLocusNames=PA1268;
OS Pseudomonas aeruginosa (strain ATCC 15692 / DSM 22644 / CIP 104116 / JCM
OS 14847 / LMG 12228 / 1C / PRS 101 / PAO1).
OC Bacteria; Proteobacteria; Gammaproteobacteria; Pseudomonadales;
OC Pseudomonadaceae; Pseudomonas.
OX NCBI_TaxID=208964;
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], FUNCTION, CATALYTIC ACTIVITY, ACTIVITY
RP REGULATION, BIOPHYSICOCHEMICAL PROPERTIES, ROLE IN VIRULENCE, AND
RP MUTAGENESIS OF VAL-60; CYS-88 AND CYS-236.
RC STRAIN=PAK;
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=ATCC 15692 / DSM 22644 / CIP 104116 / JCM 14847 / LMG 12228 / 1C /
RC PRS 101 / PAO1;
RX PubMed=10984043; DOI=10.1038/35023079;
RA Stover C.K., Pham X.-Q.T., Erwin A.L., Mizoguchi S.D., Warrener P.,
RA Hickey M.J., Brinkman F.S.L., Hufnagle W.O., Kowalik D.J., Lagrou M.,
RA Garber R.L., Goltry L., Tolentino E., Westbrock-Wadman S., Yuan Y.,
RA Brody L.L., Coulter S.N., Folger K.R., Kas A., Larbig K., Lim R.M.,
RA Smith K.A., Spencer D.H., Wong G.K.-S., Wu Z., Paulsen I.T., Reizer J.,
RA Saier M.H. Jr., Hancock R.E.W., Lory S., Olson M.V.;
RT "Complete genome sequence of Pseudomonas aeruginosa PAO1, an opportunistic
RT pathogen.";
RL Nature 406:959-964(2000).
RN [3]
RP FUNCTION, CATALYTIC ACTIVITY, SUBSTRATE SPECIFICITY, BIOPHYSICOCHEMICAL
RP PROPERTIES, AND ACTIVITY REGULATION.
RX PubMed=20665524; DOI=10.1002/elps.201000187;
RA Gavina J.M., White C.E., Finan T.M., Britz-McKibbin P.;
RT "Determination of 4-hydroxyproline-2-epimerase activity by capillary
RT electrophoresis: A stereoselective platform for inhibitor screening of
RT amino acid isomerases.";
RL Electrophoresis 31:2831-2837(2010).
RN [4]
RP FUNCTION, CATALYTIC ACTIVITY, AND INDUCTION.
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).
RN [5]
RP X-RAY CRYSTALLOGRAPHY (2.13 ANGSTROMS).
RG Midwest center for structural genomics (MCSG);
RT "The crystal structure of PA1268 solved by sulfur SAD.";
RL Submitted (DEC-2005) to the PDB data bank.
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. Cannot use L-
CC proline, trans-3-hydroxy-L-proline (t3LHyp) and pyrrolidone-5-
CC carboxylate (P5C) as substrate. {ECO:0000269|PubMed:17849014,
CC ECO:0000269|PubMed:20665524, 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:20665524, ECO:0000269|PubMed:24980702};
CC -!- ACTIVITY REGULATION: Inhibited by iodoacetate, iodoacetamide and by
CC high amounts (10 mM) of pyrrole-2-carboxylate (PYC). Not inhibited by
CC PYC at 1 mM. {ECO:0000269|PubMed:17849014,
CC ECO:0000269|PubMed:20665524}.
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=15.9 mM for 4-hydroxy-L-proline {ECO:0000269|PubMed:17849014};
CC KM=18.5 mM for 4-hydroxy-D-proline {ECO:0000269|PubMed:17849014};
CC KM=2.4 mM for trans-4-hydroxy-L-proline
CC {ECO:0000269|PubMed:20665524};
CC KM=1.6 mM for cis-4-hydroxy-D-proline {ECO:0000269|PubMed:20665524};
CC Vmax=1.65 uM/sec/mg enzyme with 4-hydroxy-L-proline as substrate (at
CC 37 degrees Celsius) {ECO:0000269|PubMed:17849014};
CC Vmax=2.4 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 -!- INDUCTION: Is up-regulated when the bacterium is grown on t4LHyp or
CC t3LHyp as sole carbon source. {ECO:0000269|PubMed:24980702}.
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; EF495341; ABS82393.2; -; Genomic_DNA.
DR EMBL; AE004091; AAG04657.1; -; Genomic_DNA.
DR PIR; G83487; G83487.
DR RefSeq; NP_249959.1; NC_002516.2.
DR RefSeq; WP_003114954.1; NZ_QZGE01000005.1.
DR PDB; 2AZP; X-ray; 2.13 A; A=1-314.
DR PDBsum; 2AZP; -.
DR AlphaFoldDB; Q9I476; -.
DR SMR; Q9I476; -.
DR STRING; 287.DR97_668; -.
DR PaxDb; Q9I476; -.
DR PRIDE; Q9I476; -.
DR EnsemblBacteria; AAG04657; AAG04657; PA1268.
DR GeneID; 881376; -.
DR KEGG; pae:PA1268; -.
DR PATRIC; fig|208964.12.peg.1318; -.
DR PseudoCAP; PA1268; -.
DR HOGENOM; CLU_036729_1_0_6; -.
DR InParanoid; Q9I476; -.
DR OMA; SHVLWTG; -.
DR PhylomeDB; Q9I476; -.
DR BioCyc; MetaCyc:MON-15828; -.
DR BioCyc; PAER208964:G1FZ6-1293-MON; -.
DR BRENDA; 5.1.1.8; 5087.
DR EvolutionaryTrace; Q9I476; -.
DR Proteomes; UP000002438; Chromosome.
DR GO; GO:0047580; F:4-hydroxyproline epimerase activity; IMP:PseudoCAP.
DR InterPro; IPR008794; Pro_racemase_fam.
DR PANTHER; PTHR33442; PTHR33442; 1.
DR Pfam; PF05544; Pro_racemase; 1.
DR PIRSF; PIRSF029792; Pro_racemase; 1.
DR SFLD; SFLDS00028; Proline_Racemase; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Isomerase; Reference proteome.
FT CHAIN 1..314
FT /note="4-hydroxyproline 2-epimerase"
FT /id="PRO_0000354035"
FT ACT_SITE 88
FT /note="Proton acceptor"
FT /evidence="ECO:0000250|UniProtKB:Q4KGU2"
FT ACT_SITE 236
FT /note="Proton donor"
FT /evidence="ECO:0000250|UniProtKB:Q4KGU2"
FT BINDING 89..90
FT /ligand="substrate"
FT /evidence="ECO:0000250|UniProtKB:Q4KGU2"
FT BINDING 208
FT /ligand="substrate"
FT /evidence="ECO:0000250|UniProtKB:Q4KGU2"
FT BINDING 232
FT /ligand="substrate"
FT /evidence="ECO:0000250|UniProtKB:Q4KGU2"
FT BINDING 237..238
FT /ligand="substrate"
FT /evidence="ECO:0000250|UniProtKB:Q4KGU2"
FT MUTAGEN 60
FT /note="V->G,F: Loss of catalytic activity."
FT /evidence="ECO:0000269|PubMed:17849014"
FT MUTAGEN 88
FT /note="C->S: Loss of catalytic activity."
FT /evidence="ECO:0000269|PubMed:17849014"
FT MUTAGEN 236
FT /note="C->S: Loss of catalytic activity."
FT /evidence="ECO:0000269|PubMed:17849014"
FT CONFLICT 174
FT /note="L -> I (in Ref. 1; ABS82393)"
FT /evidence="ECO:0000305"
FT CONFLICT 194
FT /note="D -> E (in Ref. 1; ABS82393)"
FT /evidence="ECO:0000305"
FT CONFLICT 197
FT /note="D -> G (in Ref. 1; ABS82393)"
FT /evidence="ECO:0000305"
FT STRAND 2..11
FT /evidence="ECO:0007829|PDB:2AZP"
FT STRAND 14..21
FT /evidence="ECO:0007829|PDB:2AZP"
FT HELIX 31..41
FT /evidence="ECO:0007829|PDB:2AZP"
FT HELIX 43..50
FT /evidence="ECO:0007829|PDB:2AZP"
FT TURN 52..54
FT /evidence="ECO:0007829|PDB:2AZP"
FT STRAND 60..65
FT /evidence="ECO:0007829|PDB:2AZP"
FT STRAND 72..79
FT /evidence="ECO:0007829|PDB:2AZP"
FT STRAND 81..84
FT /evidence="ECO:0007829|PDB:2AZP"
FT HELIX 89..101
FT /evidence="ECO:0007829|PDB:2AZP"
FT STRAND 107..113
FT /evidence="ECO:0007829|PDB:2AZP"
FT STRAND 119..123
FT /evidence="ECO:0007829|PDB:2AZP"
FT STRAND 129..132
FT /evidence="ECO:0007829|PDB:2AZP"
FT STRAND 136..147
FT /evidence="ECO:0007829|PDB:2AZP"
FT TURN 148..150
FT /evidence="ECO:0007829|PDB:2AZP"
FT STRAND 151..169
FT /evidence="ECO:0007829|PDB:2AZP"
FT HELIX 179..195
FT /evidence="ECO:0007829|PDB:2AZP"
FT STRAND 208..215
FT /evidence="ECO:0007829|PDB:2AZP"
FT STRAND 218..225
FT /evidence="ECO:0007829|PDB:2AZP"
FT HELIX 237..249
FT /evidence="ECO:0007829|PDB:2AZP"
FT STRAND 259..262
FT /evidence="ECO:0007829|PDB:2AZP"
FT STRAND 268..275
FT /evidence="ECO:0007829|PDB:2AZP"
FT HELIX 276..278
FT /evidence="ECO:0007829|PDB:2AZP"
FT STRAND 284..290
FT /evidence="ECO:0007829|PDB:2AZP"
FT STRAND 292..302
FT /evidence="ECO:0007829|PDB:2AZP"
FT TURN 307..310
FT /evidence="ECO:0007829|PDB:2AZP"
SQ SEQUENCE 314 AA; 33528 MW; 705A54E07074432F CRC64;
MQRIRIIDSH TGGEPTRLVI GGFPDLGQGD MAERRRLLGE RHDAWRAACI LEPRGSDVLV
GALLCAPVDP EACAGVIFFN NSGYLGMCGH GTIGLVASLA HLGRIGPGVH RIETPVGEVE
ATLHEDGSVS VRNVPAYRYR RQVSVEVPGI GRVSGDIAWG GNWFFLVAGH GQRLAGDNLD
ALTAYTVAVQ QALDDQDIRG EDGGAIDHIE LFADDPHADS RNFVLCPGKA YDRSPCGTGT
SAKLACLAAD GKLLPGQPWR QASVIGSQFE GRYEWLDGQP GGPIVPTIRG RAHVSAEATL
LLADDDPFAW GIRR
