P96240 (PHEA_MYCTU) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Prephenate dehydratase
Short name=PDT
EC=4.2.1.51

Gene names

Name:	pheA
Ordered Locus Names:	Rv3838c, MT3946

Organism

Mycobacterium tuberculosis [Reference proteome] [HAMAP]

Taxonomic identifier

1773 [NCBI]

Taxonomic lineage

cellular organisms › Bacteria › Actinobacteria › Actinobacteria › Actinobacteridae › Actinomycetales › Corynebacterineae › Mycobacteriaceae › Mycobacterium › Mycobacterium tuberculosis complex

Protein attributes

Sequence length	321 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level

General annotation (Comments)

Catalytic activity	Prephenate = phenylpyruvate + H2O + CO2. Ref.3
Enzyme regulation	Allosterically regulated by all of the three aromatic amino acids (phenylalanine, tyrosine and tryptophan). Inhibited by low concentrations of aromatic amino acids and highly activated at higher concentrations. Ionic interactions are required for optimal activity. Ref.3
Pathway	Amino-acid biosynthesis; L-phenylalanine biosynthesis; phenylpyruvate from prephenate: step 1/1.
Subunit structure	Homodimer. Ref.3
Domain	Both domains are absolutely required for activity. In the absence of the ACT domain, the enzyme not only loses its regulatory activity, but also its catalytic activity. Ref.3
Miscellaneous	Was identified as a high-confidence drug target.
Sequence similarities	Contains 1 ACT domain. Contains 1 prephenate dehydratase domain.
Biophysicochemical properties	Kinetic parameters: KM=500 µM for prephenate Ref.3 Vmax=125 µmol/min/mg enzyme pH dependence: Optimum pH is 6-7. Temperature dependence: Optimum temperature is 37-42 degrees Celsius.

Ontologies

Keywords
Biological process	Amino-acid biosynthesis Aromatic amino acid biosynthesis Phenylalanine biosynthesis
Molecular function	Lyase
Technical term	Allosteric enzyme Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	L-phenylalanine biosynthetic process from chorismate via phenylpyruvate Inferred from direct assay Ref.3. Source: UniProtKB protein homotetramerization Inferred from physical interaction PubMed 18384085. Source: MTBBASE
Molecular_function	amino acid binding Inferred from direct assay Ref.3. Source: MTBBASE prephenate dehydratase activity Inferred from direct assay Ref.3. Source: UniProtKB protein homodimerization activity Inferred from direct assay Ref.3. Source: UniProtKB
Complete GO annotation...

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 321	321	Prephenate dehydratase		PRO_0000382029
Regions
	Domain	3 – 189	187	Prephenate dehydratase
	Domain	202 – 268	67	ACT
Sites
	Site	182	1	Essential for activity By similarity

Sequences

	Sequence		Length	Mass (Da)
	P96240 [UniParc]. Last modified July 1, 1997. Version 2. Checksum: A50F13226F788EE5	FASTA	321	33,633
	10 20 30 40 50 60 MVRIAYLGPE GTFTEAALVR MVAAGLVPET GPDALQRMPV ESAPAALAAV RDGGADYACV 70 80 90 100 110 120 PIENSIDGSV LPTLDSLAIG VRLQVFAETT LDVTFSIVVK PGRNAADVRT LAAFPVAAAQ 130 140 150 160 170 180 VRQWLAAHLP AADLRPAYSN ADAARQVADG LVDAAVTSPL AAARWGLAAL ADGVVDESNA 190 200 210 220 230 240 RTRFVLVGRP GPPPARTGAD RTSAVLRIDN QPGALVAALA EFGIRGIDLT RIESRPTRTE 250 260 270 280 290 300 LGTYLFFVDC VGHIDDEAVA EALKAVHRRC ADVRYLGSWP TGPAAGAQPP LVDEASRWLA 310 320 RLRAGKPEQT LVRPDDQGAQ A

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Deciphering the biology of Mycobacterium tuberculosis from the complete genome sequence." Cole S.T., Brosch R., Parkhill J., Garnier T., Churcher C.M., Harris D.E., Gordon S.V., Eiglmeier K., Gas S., Barry C.E. III, Tekaia F., Badcock K., Basham D., Brown D., Chillingworth T., Connor R., Davies R.M., Devlin K. , Feltwell T., Gentles S., Hamlin N., Holroyd S., Hornsby T., Jagels K., Krogh A., McLean J., Moule S., Murphy L.D., Oliver S., Osborne J., Quail M.A., Rajandream M.A., Rogers J., Rutter S., Seeger K., Skelton S., Squares S., Squares R., Sulston J.E., Taylor K., Whitehead S., Barrell B.G. Nature 393:537-544(1998) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. Strain: ATCC 25618 / H37Rv.
[2]	"Whole-genome comparison of Mycobacterium tuberculosis clinical and laboratory strains." Fleischmann R.D., Alland D., Eisen J.A., Carpenter L., White O., Peterson J.D., DeBoy R.T., Dodson R.J., Gwinn M.L., Haft D.H., Hickey E.K., Kolonay J.F., Nelson W.C., Umayam L.A., Ermolaeva M.D., Salzberg S.L., Delcher A., Utterback T.R. , Weidman J.F., Khouri H.M., Gill J., Mikula A., Bishai W., Jacobs W.R. Jr., Venter J.C., Fraser C.M. J. Bacteriol. 184:5479-5490(2002) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. Strain: CDC 1551 / Oshkosh.
[3]	"pheA (Rv3838c) of Mycobacterium tuberculosis encodes an allosterically regulated monofunctional prephenate dehydratase that requires both catalytic and regulatory domains for optimum activity." Prakash P., Pathak N., Hasnain S.E. J. Biol. Chem. 280:20666-20671(2005) [PubMed] [Europe PMC] [Abstract] Cited for: CATALYTIC ACTIVITY, ENZYME REGULATION, BIOPHYSICOCHEMICAL PROPERTIES, SUBUNIT, DOMAIN. Strain: ATCC 25618 / H37Rv.
[4]	"targetTB: a target identification pipeline for Mycobacterium tuberculosis through an interactome, reactome and genome-scale structural analysis." Raman K., Yeturu K., Chandra N. BMC Syst. Biol. 2:109-109(2008) [PubMed] [Europe PMC] [Abstract] Cited for: IDENTIFICATION AS A DRUG TARGET [LARGE SCALE ANALYSIS].

Cross-references

Sequence databases
EMBL GenBank DDBJ	AE000516 Genomic DNA. Translation: AAK48313.1. BX842584 Genomic DNA. Translation: CAB06203.1. AL123456 Genomic DNA. Translation: CCP46667.1.
PIR	C70653.
RefSeq	NP_218355.1. NC_000962.3. NP_338499.1. NC_002755.2. YP_006517335.1. NC_018143.1.
3D structure databases
ProteinModelPortal	P96240.
SMR	P96240. Positions 2-292.
ModBase	Search...
Protein-protein interaction databases
STRING	83332.Rv3838c.
Proteomic databases
PRIDE	P96240.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
EnsemblBacteria	AAK48313; AAK48313; MT3946.
GeneID	13317462. 886170. 922568.
KEGG	mtc:MT3946. mtu:Rv3838c. mtv:RVBD_3838c.
PATRIC	18130433. VBIMycTub22151_4304.
Organism-specific databases
TubercuList	Rv3838c.
Phylogenomic databases
eggNOG	COG0077.
HOGENOM	HOG000018970.
KO	K04518.
OMA	CRKWLDA.
ProtClustDB	PRK11898.
Enzyme and pathway databases
SABIO-RK	P96240.
UniPathway	UPA00121; UER00345.
Family and domain databases
InterPro	IPR002912. ACT_dom. IPR001086. Preph_deHydtase. IPR018528. Preph_deHydtase_CS. [Graphical view]
Pfam	PF01842. ACT. 1 hit. PF00800. PDT. 1 hit. [Graphical view]
PROSITE	PS00857. PREPHENATE_DEHYDR_1. False negative. PS00858. PREPHENATE_DEHYDR_2. 1 hit. PS51171. PREPHENATE_DEHYDR_3. 1 hit. [Graphical view]
ProtoNet	Search...

Entry information

Entry name

PHEA_MYCTU

Accession

Primary (citable) accession number: P96240
Secondary accession number(s): L0TFE5, Q7D4S0

Entry history

Integrated into UniProtKB/Swiss-Prot:	September 1, 2009
Last sequence update:	July 1, 1997
Last modified:	May 1, 2013
This is version 89 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Prokaryotic Protein Annotation Program