DB code: S00242

CATH domain 3.20.20.60 : TIM Barrel Catalytic domain
E.C. 5.4.2.9
CSA 1pym
M-CSA 1pym
MACiE M0271

CATH domain Related DB codes (homologues)
3.20.20.60 : TIM Barrel S00241 T00217 S00197 T00043 D00477

Uniprot Enzyme Name
UniprotKB Protein name Synonyms
P56839 Phosphoenolpyruvate phosphomutase
PEP phosphomutase
Phosphoenolpyruvate mutase
PEP mutase
EC 5.4.2.9

KEGG enzyme name
phosphoenolpyruvate mutase
phosphoenolpyruvate-phosphonopyruvate phosphomutase
PEP phosphomutase
phosphoenolpyruvate phosphomutase
PEPPM
PEP phosphomutase

UniprotKB: Accession Number Entry name Activity Subunit Subcellular location Cofactor
P56839 PEPM_MYTED Phosphoenolpyruvate = 3-phosphonopyruvate. Homotetramer. Magnesium.

KEGG Pathways
Map code Pathways E.C.
MAP00440 Aminophosphonate metabolism

Compound table
Cofactors Substrates Products Intermediates
KEGG-id C00305 C00074 C02798 I00001 I00002
E.C.
Compound Magnesium Phosphoenolpyruvate 3-Phosphonopyruvate Pyruvate enolate Metaphosphate
Type divalent metal (Ca2+, Mg2+) carboxyl group,phosphate group/phosphate ion carbohydrate,carboxyl group,phosphate group/phosphate ion
ChEBI 18420
 18420
 		44897
 44897
 		30935
 30935
PubChem 888
 888
 		1005
 58114173
 59658623
 1005
 58114173
 59658623
 		439811
 439811
1m1bA Bound:_MG Unbound Analogue:SPV Unbound Unbound
1m1bB Bound:_MG Unbound Analogue:SPV Unbound Unbound
1pymA Bound:_MG Unbound Unbound Intermediate-analogue:OXL Unbound
1pymB Bound:_MG Unbound Unbound Intermediate-analogue:OXL Unbound
1s2tA Unbound Unbound Unbound Unbound Unbound
1s2tB Unbound Unbound Unbound Unbound Unbound
1s2uA Unbound Unbound Unbound Unbound Unbound
1s2uB Unbound Unbound Unbound Unbound Unbound
1s2vA Bound:_MG Unbound Unbound Unbound Unbound
1s2vB Bound:_MG Unbound Unbound Unbound Unbound
1s2vC Bound:_MG Unbound Unbound Unbound Unbound
1s2vD Bound:_MG Unbound Unbound Unbound Unbound
1s2wA Unbound Unbound Unbound Unbound Transition-state-analogue:SO4

Reference for Active-site residues
resource references E.C.
literature [9], [12]

Active-site residues
PDB Catalytic residues Cofactor-binding residues Modified residues Main-chain involved in catalysis Comment
1m1bA ARG 159;HIS 190;ASN 122 ASP 85(Magnesium binding)
1m1bB ARG 159;HIS 190;ASN 122 ASP 85(Magnesium binding)
1pymA ARG 159;HIS 190;ASN 122 ASP 85(Magnesium binding)
1pymB ARG 159;HIS 190;ASN 122 ASP 85(Magnesium binding)
1s2tA ARG 159;HIS 190;ASN 122 ASP 85(Magnesium binding)
1s2tB ARG 159;HIS 190;ASN 122 ASP 85(Magnesium binding)
1s2uA ARG 159;HIS 190;ASN 122 ASP 85(Magnesium binding) mutant D58A
1s2uB ARG 159;HIS 190;ASN 122 ASP 85(Magnesium binding) mutant D58A
1s2vA ARG 159;HIS 190;ASN 122 ASP 85(Magnesium binding) invisible 123-129
1s2vB ARG 159;HIS 190;ASN 122 ASP 85(Magnesium binding) invisible 124-126
1s2vC ARG 159;HIS 190; ASP 85(Magnesium binding) invisible 121-129
1s2vD ARG 159;HIS 190; ASP 85(Magnesium binding) invisible 120-129
1s2wA ARG 159;HIS 190; ASP 85(Magnesium binding) invisible 55-63, 119-126

References for Catalytic Mechanism
References Sections No. of steps in catalysis
[1]
Fig.1, Fig.2, Fig.3, Fig.4, Fig.5, Fig.6
[3]
Scheme 2, p.4629
[5]
Scheme 2, Fig.2, p.14171-14172
[6]
p.543-544
[9]
Fig.5 II, p.10274-10275
[12]
p.4450-4452
[13]
SCHEME 1, p.13833

References
[1]
Resource
Comments
Medline ID
PubMed ID 8180189
Journal Biochemistry
Year 1994
Volume 33
Pages 5641-6
Authors Seidel HM, Knowles JR
Title Interaction of inhibitors with phosphoenolpyruvate mutase: implications for the reaction mechanism and the nature of the active site.
Related PDB
Related UniProtKB
[2]
Resource
Comments
Medline ID
PubMed ID 8948453
Journal Biochem J
Year 1995
Volume 308
Pages 931-5
Authors Chawla S, Mutenda EK, Dixon HB, Freeman S, Smith AW
Title Synthesis of 3-arsonopyruvate and its interaction with phosphoenolpyruvate mutase.
Related PDB
Related UniProtKB
[3]
Resource
Comments
Medline ID
PubMed ID 8605214
Journal Biochemistry
Year 1996
Volume 35
Pages 4628-35
Authors Kim J, Dunaway-Mariano D
Title Phosphoenolpyruvate mutase catalysis of phosphoryl transfer in phosphoenolpyruvate: kinetics and mechanism of phosphorus-carbon bond formation.
Related PDB
Related UniProtKB
[4]
Resource
Comments
Medline ID
PubMed ID 9468496
Journal J Biol Chem
Year 1998
Volume 273
Pages 4443-8
Authors Kim A, Kim J, Martin BM, Dunaway-Mariano D
Title Isolation and characterization of the carbon-phosphorus bond-forming enzyme phosphoenolpyruvate mutase from the mollusk Mytilus edulis.
Related PDB
Related UniProtKB
[5]
Resource
Comments
Medline ID
PubMed ID 10571990
Journal Biochemistry
Year 1999
Volume 38
Pages 14165-73
Authors Jia Y, Lu Z, Huang K, Herzberg O, Dunaway-Mariano D
Title Insight into the mechanism of phosphoenolpyruvate mutase catalysis derived from site-directed mutagenesis studies of active site residues.
Related PDB
Related UniProtKB
[6]
Resource
Comments X-RAY CRYSTALLOGRAPHY (1.80 ANGSTROMS).
Medline ID 99306036
PubMed ID 10378273
Journal Structure Fold Des
Year 1999
Volume 7
Pages 539-48
Authors Huang K, Li Z, Jia Y, Dunaway-Mariano D, Herzberg O
Title Helix swapping between two alpha/beta barrels: crystal structure of phosphoenolpyruvate mutase with bound Mg(2+)-oxalate.
Related PDB 1pym
Related UniProtKB P56839
[7]
Resource
Comments
Medline ID
PubMed ID 10801489
Journal Structure Fold Des
Year 2000
Volume 8
Pages 349-62
Authors Britton K, Langridge S, Baker PJ, Weeradechapon K, Sedelnikova SE, De Lucas JR, Rice DW, Turner G
Title The crystal structure and active site location of isocitrate lyase from the fungus Aspergillus nidulans.
Related PDB
Related UniProtKB
[8]
Resource
Comments
Medline ID
PubMed ID 11526312
Journal Acta Crystallogr D Biol Crystallogr
Year 2001
Volume 57
Pages 1209-18
Authors Britton KL, Abeysinghe IS, Baker PJ, Barynin V, Diehl P, Langridge SJ, McFadden BA, Sedelnikova SE, Stillman TJ, Weeradechapon K, Rice DW
Title The structure and domain organization of Escherichia coli isocitrate lyase.
Related PDB
Related UniProtKB
[9]
Resource
Comments X-RAY CRYSTALLOGRAPHY (2.25 ANGSTROMS) OF 5-294 IN COMPLEX WITH SULFOPYRUVATE, AND MUTAGENESIS OF ASP-57; ASN-121 AND HIS-189.
Medline ID
PubMed ID 12162742
Journal Biochemistry
Year 2002
Volume 41
Pages 10270-6
Authors Liu S, Lu Z, Jia Y, Dunaway-Mariano D, Herzberg O
Title Dissociative phosphoryl transfer in PEP mutase catalysis: structure of the enzyme/sulfopyruvate complex and kinetic properties of mutants.
Related PDB 1m1b
Related UniProtKB P56839
[10]
Resource
Comments
Medline ID
PubMed ID 12837791
Journal J Bacteriol
Year 2003
Volume 185
Pages 4163-71
Authors Schmitzberger F, Smith AG, Abell C, Blundell TL
Title Comparative analysis of the Escherichia coli ketopantoate hydroxymethyltransferase crystal structure confirms that it is a member of the (betaalpha)8 phosphoenolpyruvate/pyruvate superfamily.
Related PDB
Related UniProtKB
[11]
Resource
Comments
Medline ID
PubMed ID 12672809
Journal J Biol Chem
Year 2003
Volume 278
Pages 22703-8
Authors Sarkar M, Hamilton CJ, Fairlamb AH
Title Properties of phosphoenolpyruvate mutase, the first enzyme in the aminoethylphosphonate biosynthetic pathway in Trypanosoma cruzi.
Related PDB
Related UniProtKB
[12]
Resource
Comments
Medline ID
PubMed ID 15078090
Journal Biochemistry
Year 2004
Volume 43
Pages 4447-53
Authors Liu S, Lu Z, Han Y, Jia Y, Howard A, Dunaway-Mariano D, Herzberg O
Title Conformational flexibility of PEP mutase.
Related PDB 1s2t 1s2u 1s2v 1s2w
Related UniProtKB
[13]
Resource
Comments
Medline ID
PubMed ID
Journal J Phys Chem B Condens Matter Mater Surf Interfaces Biophys
Year 2005
Volume 109
Pages 13827-34
Authors Xu DG, Guo H, Liu Y, York DM
Title Theoretical studies of dissociative phosphoryl transfer in interconversion of phosphoenolpyruvate to phosphonopyruvate: Solvent effects, thio effects, and implications for enzymatic reactions.
Related PDB
Related UniProtKB

Comments
Although there have been two catalytic mechanism for this enzyme, associative mechanism and dissociative mechanism, the literature [9] and [12] suggested that the dissociative mechanism, in which pyruvate enolate and metaphosphate are formed during catalysis, must be more likely.
Thus, this enzyme catalyzes the following reaction (see [9], [12], [13]):
(A) Elimination of metaphosphate from PEP, forming pyruvate enolate:
(B) Addition of metaphosphate to the sp2 carbon of pyruvate enolate:

Created Updated
2004-04-07 2009-02-26