ID   HYEP_ENTFA              Reviewed;         354 AA.
AC   Q834W6;
DT   09-JUL-2014, integrated into UniProtKB/Swiss-Prot.
DT   01-JUN-2003, sequence version 1.
DT   03-AUG-2022, entry version 109.
DE   RecName: Full=Hydrophobic dipeptide epimerase;
DE            EC=5.1.1.-;
GN   OrderedLocusNames=EF_1511; ORFNames=I574_01909, OO5_01959;
OS   Enterococcus faecalis (strain ATCC 700802 / V583).
OC   Bacteria; Firmicutes; Bacilli; Lactobacillales; Enterococcaceae;
OC   Enterococcus.
OX   NCBI_TaxID=226185;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC   STRAIN=ATCC 700802 / V583;
RX   PubMed=12663927; DOI=10.1126/science.1080613;
RA   Paulsen I.T., Banerjei L., Myers G.S.A., Nelson K.E., Seshadri R.,
RA   Read T.D., Fouts D.E., Eisen J.A., Gill S.R., Heidelberg J.F., Tettelin H.,
RA   Dodson R.J., Umayam L.A., Brinkac L.M., Beanan M.J., Daugherty S.C.,
RA   DeBoy R.T., Durkin S.A., Kolonay J.F., Madupu R., Nelson W.C.,
RA   Vamathevan J.J., Tran B., Upton J., Hansen T., Shetty J., Khouri H.M.,
RA   Utterback T.R., Radune D., Ketchum K.A., Dougherty B.A., Fraser C.M.;
RT   "Role of mobile DNA in the evolution of vancomycin-resistant Enterococcus
RT   faecalis.";
RL   Science 299:2071-2074(2003).
RN   [2]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC   STRAIN=ATCC 700802 / V583;
RG   The Broad Institute Genomics Platform;
RG   The Broad Institute Genome Sequencing Center for Infectious Disease;
RA   Earl A., Russ C., Gilmore M., Surin D., Walker B., Young S., Zeng Q.,
RA   Gargeya S., Fitzgerald M., Haas B., Abouelleil A., Allen A.W., Alvarado L.,
RA   Arachchi H.M., Berlin A.M., Chapman S.B., Gainer-Dewar J., Goldberg J.,
RA   Griggs A., Gujja S., Hansen M., Howarth C., Imamovic A., Ireland A.,
RA   Larimer J., McCowan C., Murphy C., Pearson M., Poon T.W., Priest M.,
RA   Roberts A., Saif S., Shea T., Sisk P., Sykes S., Wortman J., Nusbaum C.,
RA   Birren B.;
RT   "The genome sequence of Enterococcus faecalis V583 (Illumina only
RT   assembly).";
RL   Submitted (MAR-2013) to the EMBL/GenBank/DDBJ databases.
RN   [3]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC   STRAIN=ATCC 700802 / V583;
RG   The Broad Institute Genomics Platform;
RG   The Broad Institute Genome Sequencing Center for Infectious Disease;
RA   Earl A., Russ C., Gilmore M., Surin D., Walker B., Young S., Zeng Q.,
RA   Gargeya S., Fitzgerald M., Haas B., Abouelleil A., Allen A.W., Alvarado L.,
RA   Arachchi H.M., Berlin A.M., Chapman S.B., Gainer-Dewar J., Goldberg J.,
RA   Griggs A., Gujja S., Hansen M., Howarth C., Imamovic A., Ireland A.,
RA   Larimer J., McCowan C., Murphy C., Pearson M., Poon T.W., Priest M.,
RA   Roberts A., Saif S., Shea T., Sisk P., Sykes S., Wortman J., Nusbaum C.,
RA   Birren B.;
RT   "The genome sequence of Enterococcus faecalis V583 (PacBio/Illumina hybrid
RT   assembly).";
RL   Submitted (MAR-2013) to the EMBL/GenBank/DDBJ databases.
RN   [4]
RP   X-RAY CRYSTALLOGRAPHY (1.70 ANGSTROMS) IN COMPLEXES WITH DIPEPTIDE AND
RP   MAGNESIUM, FUNCTION, COFACTOR, AND BIOPHYSICOCHEMICAL PROPERTIES.
RC   STRAIN=ATCC 700802 / V583;
RX   PubMed=22392983; DOI=10.1073/pnas.1112081109;
RA   Lukk T., Sakai A., Kalyanaraman C., Brown S.D., Imker H.J., Song L.,
RA   Fedorov A.A., Fedorov E.V., Toro R., Hillerich B., Seidel R.,
RA   Patskovsky Y., Vetting M.W., Nair S.K., Babbitt P.C., Almo S.C.,
RA   Gerlt J.A., Jacobson M.P.;
RT   "Homology models guide discovery of diverse enzyme specificities among
RT   dipeptide epimerases in the enolase superfamily.";
RL   Proc. Natl. Acad. Sci. U.S.A. 109:4122-4127(2012).
CC   -!- FUNCTION: Catalyzes the epimerization of L-Ile-L-Tyr to L-Ile-D-Tyr (in
CC       vitro). Catalyzes the epimerization of dipeptides, with a preference
CC       for substrates with a hydrophobic or basic amino acid in the first
CC       position, followed by an aromatic residue in the second position. Has
CC       epimerase activity with L-Ile-L-Tyr, L-Val-L-Tyr and L-Arg-L-Tyr (in
CC       vitro). {ECO:0000269|PubMed:22392983}.
CC   -!- COFACTOR:
CC       Name=Mg(2+); Xref=ChEBI:CHEBI:18420;
CC         Evidence={ECO:0000269|PubMed:22392983};
CC       Note=Binds 1 Mg(2+) ion per subunit. {ECO:0000269|PubMed:22392983};
CC   -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC       Kinetic parameters:
CC         KM=0.7 mM for L-Val-L-Tyr {ECO:0000269|PubMed:22392983};
CC         KM=1.4 mM for L-Arg-L-Tyr {ECO:0000269|PubMed:22392983};
CC         KM=0.77 mM for L-Ile-L-Tyr {ECO:0000269|PubMed:22392983};
CC         Note=kcat is 9.2 sec(-1) for epimerization of L-Ile-L-Tyr. kcat is
CC         8.7 sec(-1) for epimerization of L-Val-L-Tyr. kcat is 15 sec(-1) for
CC         epimerization of L-Arg-L-Tyr.;
CC   -!- MISCELLANEOUS: Part of a large, functionally divergent protein family.
CC       Protein modeling and substrate docking was used to predict the
CC       substrate specificity, prior to biochemical analysis.
CC   -!- SIMILARITY: Belongs to the mandelate racemase/muconate lactonizing
CC       enzyme family. {ECO:0000305}.
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DR   EMBL; AE016830; AAO81302.1; -; Genomic_DNA.
DR   EMBL; AHYN01000009; EOT50195.1; -; Genomic_DNA.
DR   EMBL; ASWP01000006; EOT84729.1; -; Genomic_DNA.
DR   RefSeq; NP_815232.1; NC_004668.1.
DR   RefSeq; WP_002382304.1; NZ_KE136528.1.
DR   PDB; 3JVA; X-ray; 1.70 A; A/B/C/D/E/F/G/H=1-354.
DR   PDB; 3JW7; X-ray; 1.80 A; A/B/C/D/E/F/G/H=1-354.
DR   PDB; 3JZU; X-ray; 2.00 A; A/B/C/D/E/F/G/H=1-354.
DR   PDB; 3K1G; X-ray; 2.00 A; A/B/C/D/E/F/G/H=1-354.
DR   PDB; 3KUM; X-ray; 1.90 A; A/B/C/D/E/F/G/H=1-354.
DR   PDBsum; 3JVA; -.
DR   PDBsum; 3JW7; -.
DR   PDBsum; 3JZU; -.
DR   PDBsum; 3K1G; -.
DR   PDBsum; 3KUM; -.
DR   AlphaFoldDB; Q834W6; -.
DR   SMR; Q834W6; -.
DR   STRING; 226185.EF_1511; -.
DR   EnsemblBacteria; AAO81302; AAO81302; EF_1511.
DR   KEGG; efa:EF1511; -.
DR   PATRIC; fig|226185.45.peg.1989; -.
DR   eggNOG; COG4948; Bacteria.
DR   HOGENOM; CLU_030273_4_0_9; -.
DR   OMA; MFGCYSD; -.
DR   EvolutionaryTrace; Q834W6; -.
DR   Proteomes; UP000001415; Chromosome.
DR   GO; GO:0000287; F:magnesium ion binding; IDA:UniProtKB.
DR   GO; GO:0016854; F:racemase and epimerase activity; IDA:UniProtKB.
DR   GO; GO:0016855; F:racemase and epimerase activity, acting on amino acids and derivatives; IEA:InterPro.
DR   GO; GO:0009063; P:cellular amino acid catabolic process; IEA:InterPro.
DR   GO; GO:0006518; P:peptide metabolic process; IDA:UniProtKB.
DR   CDD; cd03319; L-Ala-DL-Glu_epimerase; 1.
DR   Gene3D; 3.20.20.120; -; 1.
DR   Gene3D; 3.30.390.10; -; 1.
DR   InterPro; IPR034603; Dipeptide_epimerase.
DR   InterPro; IPR036849; Enolase-like_C_sf.
DR   InterPro; IPR029017; Enolase-like_N.
DR   InterPro; IPR029065; Enolase_C-like.
DR   InterPro; IPR018110; Mandel_Rmase/mucon_lact_enz_CS.
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   SMART; SM00922; MR_MLE; 1.
DR   SUPFAM; SSF51604; SSF51604; 1.
DR   SUPFAM; SSF54826; SSF54826; 1.
DR   PROSITE; PS00909; MR_MLE_2; 1.
PE   1: Evidence at protein level;
KW   3D-structure; Isomerase; Magnesium; Metal-binding; Reference proteome.
FT   CHAIN           1..354
FT                   /note="Hydrophobic dipeptide epimerase"
FT                   /id="PRO_0000429653"
FT   BINDING         134
FT                   /ligand="substrate"
FT   BINDING         159..161
FT                   /ligand="substrate"
FT   BINDING         159
FT                   /ligand="substrate"
FT   BINDING         189
FT                   /ligand="Mg(2+)"
FT                   /ligand_id="ChEBI:CHEBI:18420"
FT   BINDING         191
FT                   /ligand="substrate"
FT   BINDING         215
FT                   /ligand="Mg(2+)"
FT                   /ligand_id="ChEBI:CHEBI:18420"
FT   BINDING         240
FT                   /ligand="Mg(2+)"
FT                   /ligand_id="ChEBI:CHEBI:18420"
FT   BINDING         264
FT                   /ligand="substrate"
FT   BINDING         292..295
FT                   /ligand="substrate"
FT   BINDING         318..320
FT                   /ligand="substrate"
FT   STRAND          3..21
FT                   /evidence="ECO:0007829|PDB:3JVA"
FT   STRAND          24..38
FT                   /evidence="ECO:0007829|PDB:3JVA"
FT   STRAND          43..48
FT                   /evidence="ECO:0007829|PDB:3JVA"
FT   TURN            52..54
FT                   /evidence="ECO:0007829|PDB:3JVA"
FT   HELIX           59..70
FT                   /evidence="ECO:0007829|PDB:3JVA"
FT   TURN            73..75
FT                   /evidence="ECO:0007829|PDB:3JW7"
FT   HELIX           81..91
FT                   /evidence="ECO:0007829|PDB:3JVA"
FT   HELIX           96..114
FT                   /evidence="ECO:0007829|PDB:3JVA"
FT   HELIX           118..121
FT                   /evidence="ECO:0007829|PDB:3JVA"
FT   STRAND          127..130
FT                   /evidence="ECO:0007829|PDB:3JVA"
FT   STRAND          133..135
FT                   /evidence="ECO:0007829|PDB:3JVA"
FT   HELIX           140..152
FT                   /evidence="ECO:0007829|PDB:3JVA"
FT   STRAND          156..161
FT                   /evidence="ECO:0007829|PDB:3JVA"
FT   HELIX           166..180
FT                   /evidence="ECO:0007829|PDB:3JVA"
FT   STRAND          184..189
FT                   /evidence="ECO:0007829|PDB:3JVA"
FT   HELIX           196..205
FT                   /evidence="ECO:0007829|PDB:3JVA"
FT   TURN            206..208
FT                   /evidence="ECO:0007829|PDB:3JVA"
FT   STRAND          211..215
FT                   /evidence="ECO:0007829|PDB:3JVA"
FT   HELIX           223..232
FT                   /evidence="ECO:0007829|PDB:3JVA"
FT   STRAND          234..240
FT                   /evidence="ECO:0007829|PDB:3JVA"
FT   HELIX           246..255
FT                   /evidence="ECO:0007829|PDB:3JVA"
FT   STRAND          259..263
FT                   /evidence="ECO:0007829|PDB:3JVA"
FT   HELIX           265..268
FT                   /evidence="ECO:0007829|PDB:3JVA"
FT   HELIX           271..283
FT                   /evidence="ECO:0007829|PDB:3JVA"
FT   STRAND          287..290
FT                   /evidence="ECO:0007829|PDB:3JVA"
FT   HELIX           298..310
FT                   /evidence="ECO:0007829|PDB:3JVA"
FT   STRAND          314..317
FT                   /evidence="ECO:0007829|PDB:3JVA"
FT   HELIX           321..324
FT                   /evidence="ECO:0007829|PDB:3JVA"
FT   STRAND          325..327
FT                   /evidence="ECO:0007829|PDB:3JVA"
FT   STRAND          329..334
FT                   /evidence="ECO:0007829|PDB:3JVA"
FT   STRAND          340..343
FT                   /evidence="ECO:0007829|PDB:3JVA"
FT   STRAND          346..349
FT                   /evidence="ECO:0007829|PDB:3JVA"
SQ   SEQUENCE   354 AA;  37807 MW;  D94FBCE053A4D531 CRC64;
     MKIKQVHVRA SKIKLKETFT IALGTIESAD SAIVEIETEE GLVGYGEGGP GIFITGETLA
     GTLETIELFG QAIIGLNPFN IEKIHEVMDK ISAFAPAAKA AIDIACYDLM GQKAQLPLYQ
     LLGGYDNQVI TDITLGIDEP NVMAQKAVEK VKLGFDTLKI KVGTGIEADI ARVKAIREAV
     GFDIKLRLDA NQAWTPKDAV KAIQALADYQ IELVEQPVKR RDLEGLKYVT SQVNTTIMAD
     ESCFDAQDAL ELVKKGTVDV INIKLMKCGG IHEALKINQI CETAGIECMI GCMAEETTIG
     ITAAAHLAAA QKNITRADLD ATFGLETAPV TGGVSLEAKP LLELGEAAGL GISH