DB code: S00287

RLCP classification 3.943.120000.356 : Transfer
CATH domain 3.40.50.2020 : Rossmann fold Catalytic domain
E.C. 2.4.2.9
CSA 1bd3
M-CSA 1bd3
MACiE

CATH domain Related DB codes (homologues)
3.40.50.2020 : Rossmann fold S00288 S00289 D00131

Uniprot Enzyme Name
UniprotKB Protein name Synonyms Pfam
Q26998 Uracil phosphoribosyltransferase
EC 2.4.2.9
UMP pyrophosphorylase
UPRTase
UPRT
[Graphical View]
P70881 Uracil phosphoribosyltransferase
EC 2.4.2.9
UMP pyrophosphorylase
UPRTase
PF00156 (Pribosyltran)
[Graphical View]

KEGG enzyme name
uracil phosphoribosyltransferase
UMP pyrophosphorylase
UPRTase
UMP:pyrophosphate phosphoribosyltransferase
uridine 5'-phosphate pyrophosphorylase
uridine monophosphate pyrophosphorylase
uridylate pyrophosphorylase
uridylic pyrophosphorylase

UniprotKB: Accession Number Entry name Activity Subunit Subcellular location Cofactor
Q26998 UPP_TOXGO UMP + diphosphate = uracil + 5-phospho-alpha- D-ribose 1-diphosphate. Monomer.
P70881 UPP_BACCL UMP + diphosphate = uracil + 5-phospho-alpha- D-ribose 1-diphosphate. Homodimer. Magnesium (By similarity).

KEGG Pathways
Map code Pathways E.C.
MAP00240 Pyrimidine metabolism

Compound table
Cofactors Substrates Products Intermediates
KEGG-id C00305 C00106 C00119 C00105 C00013
E.C.
Compound magnesium Uracil 5-Phospho-alpha-D-ribose 1-diphosphate UMP Pyrophosphate
Type divalent metal (Ca2+, Mg2+) amide group,aromatic ring (with nitrogen atoms) carbohydrate,phosphate group/phosphate ion amide group,nucleotide phosphate group/phosphate ion
ChEBI 18420
 18420
 		17568
 17568
 		17111
 17111
 		16695
 16695
 		29888
 29888
PubChem 888
 888
 		1174
 1174
 		7339
 7339
 		6030
 6030
 		1023
 21961011
 1023
 21961011
1bd3A Unbound Unbound Unbound Unbound Unbound
1bd3B Unbound Unbound Unbound Unbound Unbound
1bd3C Unbound Unbound Unbound Unbound Unbound
1bd3D Unbound Unbound Unbound Unbound Unbound
1bd4A Unbound Bound:URA Unbound Unbound Unbound
1bd4B Unbound Bound:URA Unbound Unbound Unbound
1bd4C Unbound Bound:URA Unbound Unbound Unbound
1bd4D Unbound Bound:URA Unbound Unbound Unbound
1upfA Unbound Analogue:URF Unbound Unbound Analogue:SO4
1upfB Unbound Analogue:URF Unbound Unbound Analogue:SO4
1upfC Unbound Analogue:URF Unbound Unbound Analogue:SO4
1upfD Unbound Analogue:URF Unbound Unbound Analogue:SO4
1upuA Unbound Unbound Unbound Bound:U5P Unbound
1upuB Unbound Unbound Unbound Bound:U5P Unbound
1upuC Unbound Unbound Unbound Bound:U5P Unbound
1upuD Unbound Unbound Unbound Bound:U5P Unbound
1jlrA Unbound Unbound Unbound Unbound Analogue:PO4
1jlrB Unbound Unbound Unbound Unbound Analogue:PO4
1jlrC Unbound Unbound Unbound Unbound Analogue:PO4
1jlrD Unbound Unbound Unbound Unbound Analogue:PO4
1jlsA Unbound Bound:URA Unbound Unbound Analogue:PO4
1jlsB Bound:_MG Bound:URA Bound:PRP Unbound Unbound
1jlsC Unbound Bound:URA Unbound Unbound Unbound
1jlsD Unbound Bound:URA Unbound Unbound Analogue:PO4
1i5eA Unbound Unbound Unbound Bound:U5P Unbound
1i5eB Unbound Unbound Unbound Bound:U5P Unbound

Reference for Active-site residues
resource references E.C.

Active-site residues
PDB Catalytic residues Cofactor-binding residues Modified residues Main-chain involved in catalysis Comment
1bd3A ASP 164;ASP 235;ASP 238
1bd3B ASP 164;ASP 235;ASP 238
1bd3C ASP 164;ASP 235;ASP 238
1bd3D ASP 164;ASP 235;ASP 238
1bd4A ASP 164;ASP 235;ASP 238
1bd4B ASP 164;ASP 235;ASP 238
1bd4C ASP 164;ASP 235;ASP 238
1bd4D ASP 164;ASP 235;ASP 238
1upfA ASP 164;ASP 235;ASP 238
1upfB ASP 164;ASP 235;ASP 238
1upfC ASP 164;ASP 235;ASP 238
1upfD ASP 164;ASP 235;ASP 238
1upuA ASP 164;ASP 235;ASP 238
1upuB ASP 164;ASP 235;ASP 238
1upuC ASP 164;ASP 235;ASP 238
1upuD ASP 164;ASP 235;ASP 238
1jlrA ASP 164;ASP 235;ASP 238
1jlrB ASP 164;ASP 235;ASP 238
1jlrC ASP 164;ASP 235;ASP 238
1jlrD ASP 164;ASP 235;ASP 238
1jlsA ASP 164;ASP 235;ASP 238
1jlsB ASP 164;ASP 235;ASP 238
1jlsC ASP 164;ASP 235;ASP 238
1jlsD ASP 164;ASP 235;ASP 238
1i5eA ASP 131;ASP 200;ASP 203
1i5eB ASP 131;ASP 200;ASP 203

References for Catalytic Mechanism
References Sections No. of steps in catalysis
[3]
p.3228-3229
[5]
p.81-83
[6]
p.943-944, Fig.8 1

References
[1]
Resource
Comments
Medline ID
PubMed ID 8080452
Journal Biochem Pharmacol
Year 1994
Volume 48
Pages 781-92
Authors Iltzsch MH, Tankersley KO
Title Structure-activity relationship of ligands of uracil phosphoribosyltransferase from Toxoplasma gondii.
Related PDB
Related UniProtKB
[2]
Resource
Comments
Medline ID
PubMed ID 8765224
Journal Biochim Biophys Acta
Year 1996
Volume 1296
Pages 16-22
Authors Linde L, Jensen KF
Title Uracil phosphoribosyltransferase from the extreme thermoacidophilic archaebacterium Sulfolobus shibatae is an allosteric enzyme, activated by GTP and inhibited by CTP.
Related PDB
Related UniProtKB
[3]
Resource
Comments
Medline ID
PubMed ID 9628859
Journal EMBO J
Year 1998
Volume 17
Pages 3219-32
Authors Schumacher MA, Carter D, Scott DM, Roos DS, Ullman B, Brennan RG
Title Crystal structures of Toxoplasma gondii uracil phosphoribosyltransferase reveal the atomic basis of pyrimidine discrimination and prodrug binding.
Related PDB 1bd3 1bd4 1upf 1upu
Related UniProtKB Q26998
[4]
Resource
Comments
Medline ID
PubMed ID 10079076
Journal Biochemistry
Year 1999
Volume 38
Pages 3327-34
Authors Lundegaard C, Jensen KF
Title Kinetic mechanism of uracil phosphoribosyltransferase from Escherichia coli and catalytic importance of the conserved proline in the PRPP binding site.
Related PDB
Related UniProtKB
[5]
Resource
Comments
Medline ID
PubMed ID 11773618
Journal Proc Natl Acad Sci U S A
Year 2002
Volume 99
Pages 78-83
Authors Schumacher MA, Bashor CJ, Song MH, Otsu K, Zhu S, Parry RJ, Ullman B, Brennan RG
Title The structural mechanism of GTP stabilized oligomerization and catalytic activation of the Toxoplasma gondii uracil phosphoribosyltransferase.
Related PDB 1jlr 1jls
Related UniProtKB
[6]
Resource
Comments
Medline ID
PubMed ID 12037295
Journal Acta Crystallogr D Biol Crystallogr
Year 2002
Volume 58
Pages 936-45
Authors Kadziola A, Neuhard J, Larsen S
Title Structure of product-bound Bacillus caldolyticus uracil phosphoribosyltransferase confirms ordered sequential substrate binding.
Related PDB 1i5e
Related UniProtKB
[7]
Resource
Comments
Medline ID
PubMed ID 12482852
Journal J Biol Chem
Year 2003
Volume 278
Pages 6921-7
Authors Grabner GK, Switzer RL
Title Kinetic studies of the uracil phosphoribosyltransferase reaction catalyzed by the Bacillus subtilis pyrimidine attenuation regulatory protein PyrR.
Related PDB
Related UniProtKB

Comments
According to the literature [6], one of the substrates, uracil can adopt its tautomeric enol form, with a hydroxyl group at O2 protonated from N1 atom. This enol form of uracil can donate the proton to the carboxylate of Asp235 (Asp200 at PDB 1i5e), acting as a general base, and the alpha-phosphate group of another substrate, PRPP. The movement of the proton towards OP1 of the alpha-phosphate of PRPP activates uracil itself as a nucleophile and the pyrophosphate of PRPP as a leaving group.
The paper [5] also suggested that Asp235 might act as the general base, or a proton shuttle, whilst the paper itself also suggested substrate-assisted abstraction of N1 proton of uracil by alpha-phosphate of PRPP. Moreover, Asp238 increased the pKa of the sidechain of Asp235, which can abstract a proton from the scissile pyrophosphate.
Moreover, the paper [6] suggested that Asp164 (Asp131 at 1i5e) might stabilize the positively charged oxocarbenium-like transition state.
Although the reaction seems to be dependent on magnesium, its role has not been elucidated. As it seems to be bound to beta-phosphate group of PRPP (PDB 1jls), it may contribute to the leaving group.
The reaction between the uracil N1 nucleophile and the PRPP C1' atom might proceed through an SN1 or SN2-like mechanism, or mixture of these mechanisms, to produce UMP and pyrophosphate, according to the paper [5].

Created Updated
2002-05-02 2009-03-30