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Database: UniProt
Entry: P9WIC3
LinkDB: P9WIC3
Original site: P9WIC3 
ID   PHEA_MYCTU              Reviewed;         321 AA.
AC   P9WIC3; L0TFE5; P96240; Q7D4S0;
DT   16-APR-2014, integrated into UniProtKB/Swiss-Prot.
DT   16-APR-2014, sequence version 1.
DT   25-MAY-2022, entry version 38.
DE   RecName: Full=Prephenate dehydratase;
DE            Short=PDT;
DE            EC=4.2.1.51;
GN   Name=pheA; OrderedLocusNames=Rv3838c;
OS   Mycobacterium tuberculosis (strain ATCC 25618 / H37Rv).
OC   Bacteria; Actinobacteria; Corynebacteriales; Mycobacteriaceae;
OC   Mycobacterium; Mycobacterium tuberculosis complex.
OX   NCBI_TaxID=83332;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC   STRAIN=ATCC 25618 / H37Rv;
RX   PubMed=9634230; DOI=10.1038/31159;
RA   Cole S.T., Brosch R., Parkhill J., Garnier T., Churcher C.M., Harris D.E.,
RA   Gordon S.V., Eiglmeier K., Gas S., Barry C.E. III, Tekaia F., Badcock K.,
RA   Basham D., Brown D., Chillingworth T., Connor R., Davies R.M., Devlin K.,
RA   Feltwell T., Gentles S., Hamlin N., Holroyd S., Hornsby T., Jagels K.,
RA   Krogh A., McLean J., Moule S., Murphy L.D., Oliver S., Osborne J.,
RA   Quail M.A., Rajandream M.A., Rogers J., Rutter S., Seeger K., Skelton S.,
RA   Squares S., Squares R., Sulston J.E., Taylor K., Whitehead S.,
RA   Barrell B.G.;
RT   "Deciphering the biology of Mycobacterium tuberculosis from the complete
RT   genome sequence.";
RL   Nature 393:537-544(1998).
RN   [2]
RP   CATALYTIC ACTIVITY, ACTIVITY REGULATION, BIOPHYSICOCHEMICAL PROPERTIES,
RP   SUBUNIT, AND DOMAIN.
RC   STRAIN=ATCC 25618 / H37Rv;
RX   PubMed=15753077; DOI=10.1074/jbc.m502107200;
RA   Prakash P., Pathak N., Hasnain S.E.;
RT   "pheA (Rv3838c) of Mycobacterium tuberculosis encodes an allosterically
RT   regulated monofunctional prephenate dehydratase that requires both
RT   catalytic and regulatory domains for optimum activity.";
RL   J. Biol. Chem. 280:20666-20671(2005).
RN   [3]
RP   IDENTIFICATION AS A DRUG TARGET [LARGE SCALE ANALYSIS].
RX   PubMed=19099550; DOI=10.1186/1752-0509-2-109;
RA   Raman K., Yeturu K., Chandra N.;
RT   "targetTB: a target identification pipeline for Mycobacterium tuberculosis
RT   through an interactome, reactome and genome-scale structural analysis.";
RL   BMC Syst. Biol. 2:109-109(2008).
RN   [4]
RP   IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC   STRAIN=ATCC 25618 / H37Rv;
RX   PubMed=21969609; DOI=10.1074/mcp.m111.011627;
RA   Kelkar D.S., Kumar D., Kumar P., Balakrishnan L., Muthusamy B., Yadav A.K.,
RA   Shrivastava P., Marimuthu A., Anand S., Sundaram H., Kingsbury R.,
RA   Harsha H.C., Nair B., Prasad T.S., Chauhan D.S., Katoch K., Katoch V.M.,
RA   Kumar P., Chaerkady R., Ramachandran S., Dash D., Pandey A.;
RT   "Proteogenomic analysis of Mycobacterium tuberculosis by high resolution
RT   mass spectrometry.";
RL   Mol. Cell. Proteomics 10:M111.011627-M111.011627(2011).
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=H(+) + prephenate = 3-phenylpyruvate + CO2 + H2O;
CC         Xref=Rhea:RHEA:21648, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378,
CC         ChEBI:CHEBI:16526, ChEBI:CHEBI:18005, ChEBI:CHEBI:29934; EC=4.2.1.51;
CC         Evidence={ECO:0000269|PubMed:15753077};
CC   -!- ACTIVITY REGULATION: Allosterically regulated by all of the three
CC       aromatic amino acids (phenylalanine, tyrosine and tryptophan).
CC       Inhibited by low concentrations of aromatic amino acids and highly
CC       activated at higher concentrations. Ionic interactions are required for
CC       optimal activity. {ECO:0000269|PubMed:15753077}.
CC   -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC       Kinetic parameters:
CC         KM=500 uM for prephenate {ECO:0000269|PubMed:15753077};
CC         Vmax=125 umol/min/mg enzyme {ECO:0000269|PubMed:15753077};
CC       pH dependence:
CC         Optimum pH is 6-7. {ECO:0000269|PubMed:15753077};
CC       Temperature dependence:
CC         Optimum temperature is 37-42 degrees Celsius.
CC         {ECO:0000269|PubMed:15753077};
CC   -!- PATHWAY: Amino-acid biosynthesis; L-phenylalanine biosynthesis;
CC       phenylpyruvate from prephenate: step 1/1.
CC   -!- SUBUNIT: Homodimer. {ECO:0000269|PubMed:15753077}.
CC   -!- DOMAIN: Both domains are absolutely required for activity. In the
CC       absence of the ACT domain, the enzyme not only loses its regulatory
CC       activity, but also its catalytic activity.
CC       {ECO:0000269|PubMed:15753077}.
CC   -!- MISCELLANEOUS: Was identified as a high-confidence drug target.
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DR   EMBL; AL123456; CCP46667.1; -; Genomic_DNA.
DR   PIR; C70653; C70653.
DR   RefSeq; NP_218355.1; NC_000962.3.
DR   RefSeq; WP_003420906.1; NZ_NVQJ01000022.1.
DR   AlphaFoldDB; P9WIC3; -.
DR   SMR; P9WIC3; -.
DR   STRING; 83332.Rv3838c; -.
DR   PaxDb; P9WIC3; -.
DR   DNASU; 886170; -.
DR   GeneID; 886170; -.
DR   KEGG; mtu:Rv3838c; -.
DR   TubercuList; Rv3838c; -.
DR   eggNOG; COG0077; Bacteria.
DR   OMA; PLMIYRE; -.
DR   PhylomeDB; P9WIC3; -.
DR   BRENDA; 4.2.1.51; 3445.
DR   UniPathway; UPA00121; UER00345.
DR   Proteomes; UP000001584; Chromosome.
DR   GO; GO:0005737; C:cytoplasm; IBA:GO_Central.
DR   GO; GO:0016597; F:amino acid binding; IDA:MTBBASE.
DR   GO; GO:0004664; F:prephenate dehydratase activity; IDA:MTBBASE.
DR   GO; GO:0042803; F:protein homodimerization activity; IDA:UniProtKB.
DR   GO; GO:0009094; P:L-phenylalanine biosynthetic process; IBA:GO_Central.
DR   GO; GO:0033585; P:L-phenylalanine biosynthetic process from chorismate via phenylpyruvate; IDA:MTBBASE.
DR   InterPro; IPR045865; ACT-like_dom_sf.
DR   InterPro; IPR002912; ACT_dom.
DR   InterPro; IPR008242; Chor_mutase/pphenate_deHydtase.
DR   InterPro; IPR001086; Preph_deHydtase.
DR   InterPro; IPR018528; Preph_deHydtase_CS.
DR   Pfam; PF01842; ACT; 1.
DR   Pfam; PF00800; PDT; 1.
DR   PIRSF; PIRSF001500; Chor_mut_pdt_Ppr; 1.
DR   SUPFAM; SSF55021; SSF55021; 1.
DR   PROSITE; PS51671; ACT; 1.
DR   PROSITE; PS00858; PREPHENATE_DEHYDR_2; 1.
DR   PROSITE; PS51171; PREPHENATE_DEHYDR_3; 1.
PE   1: Evidence at protein level;
KW   Allosteric enzyme; Amino-acid biosynthesis;
KW   Aromatic amino acid biosynthesis; Lyase; Phenylalanine biosynthesis;
KW   Reference proteome.
FT   CHAIN           1..321
FT                   /note="Prephenate dehydratase"
FT                   /id="PRO_0000382029"
FT   DOMAIN          3..189
FT                   /note="Prephenate dehydratase"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00517"
FT   DOMAIN          203..280
FT                   /note="ACT"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU01007"
FT   SITE            182
FT                   /note="Essential for activity"
FT                   /evidence="ECO:0000250"
SQ   SEQUENCE   321 AA;  33633 MW;  A50F13226F788EE5 CRC64;
     MVRIAYLGPE GTFTEAALVR MVAAGLVPET GPDALQRMPV ESAPAALAAV RDGGADYACV
     PIENSIDGSV LPTLDSLAIG VRLQVFAETT LDVTFSIVVK PGRNAADVRT LAAFPVAAAQ
     VRQWLAAHLP AADLRPAYSN ADAARQVADG LVDAAVTSPL AAARWGLAAL ADGVVDESNA
     RTRFVLVGRP GPPPARTGAD RTSAVLRIDN QPGALVAALA EFGIRGIDLT RIESRPTRTE
     LGTYLFFVDC VGHIDDEAVA EALKAVHRRC ADVRYLGSWP TGPAAGAQPP LVDEASRWLA
     RLRAGKPEQT LVRPDDQGAQ A
//
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