PDBsum entry 1u1c

Transferase

PDB id

1u1c

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Contents

			Protein chains

					(+ 0 more) 253 a.a. *

			Ligands

					PO4 ×6


					BAU ×6

			Metals

					__K ×3

			Waters ×561

* Residue conservation analysis

PDB id:

1u1c

Links

Name:

Transferase

Title:

Structure of e. Coli uridine phosphorylase complexed to 5- benzylacyclouridine (bau)

Structure:

Uridine phosphorylase. Chain: a, b, c, d, e, f. Synonym: urdpase. Upase. Engineered: yes

Source:

Escherichia coli. Organism_taxid: 562. Gene: udp, b3831. Expressed in: escherichia coli. Expression_system_taxid: 562.

Biol. unit:

Hexamer (from PQS)

Resolution:

2.20Å

R-factor:

0.219

R-free:

0.249

Authors:

W.Bu,E.C.Settembre,S.E.Ealick

Key ref:

W.Bu et al. (2005). Structural basis for inhibition of Escherichia coli uridine phosphorylase by 5-substituted acyclouridines. Acta Crystallogr D Biol Crystallogr, 61, 863-872. PubMed id: 15983408 DOI: 10.1107/S0907444905007882

Date:

15-Jul-04

Release date:

05-Jul-05

PROCHECK

	Headers

	References

Protein chains

P12758 (UDP_ECOLI) - Uridine phosphorylase from Escherichia coli (strain K12)

Seq: Struc:					253 a.a. 253 a.a.

Key:

PfamA domain

Secondary structure

CATH domain



		Enzyme reactions

Enzyme class:

E.C.2.4.2.3 - uridine phosphorylase.

[IntEnz] [ExPASy] [KEGG] [BRENDA]

Reaction:

uridine + phosphate = alpha-D-ribose 1-phosphate + uracil

uridine
Bound ligand (Het Group name = PO4)
corresponds exactly

phosphate
Bound ligand (Het Group name = BAU)
matches with 54.17% similarity

alpha-D-ribose 1-phosphate

uracil

Molecule diagrams generated from .mol files obtained from the KEGG ftp site

reference

DOI no: 10.1107/S0907444905007882	Acta Crystallogr D Biol Crystallogr 61:863-872 (2005)
PubMed id: 15983408

Structural basis for inhibition of Escherichia coli uridine phosphorylase by 5-substituted acyclouridines.
W.Bu, E.C.Settembre, M.H.el Kouni, S.E.Ealick.

ABSTRACT

Uridine phosphorylase (UP) catalyzes the reversible phosphorolysis of uridine to uracil and ribose 1-phosphate and is a key enzyme in the pyrimidine-salvage pathway. Escherichia coli UP is structurally homologous to E. coli purine nucleoside phosphorylase and other members of the type I family of nucleoside phosphorylases. The structures of 5-benzylacyclouridine, 5-phenylthioacyclouridine, 5-phenylselenenylacyclouridine, 5-m-benzyloxybenzyl acyclouridine and 5-m-benzyloxybenzyl barbituric acid acyclonucleoside bound to the active site of E. coli UP have been determined, with resolutions ranging from 1.95 to 2.3 A. For all five complexes the acyclo sugar moiety binds to the active site in a conformation that mimics the ribose ring of the natural substrates. Surprisingly, the terminal hydroxyl group occupies the position of the nonessential 5'-hydroxyl substituent of the substrate rather than the 3'-hydroxyl group, which is normally required for catalytic activity. Until recently, inhibitors of UP were designed with limited structural knowledge of the active-site residues. These structures explain the basis of inhibition for this series of acyclouridine analogs and suggest possible additional avenues for future drug-design efforts. Furthermore, the studies can be extended to design inhibitors of human UP, for which no X-ray structure is available.

Selected figure(s)



	Figure 2. Figure 2 Structure of UP shown in ribbon representation. (a) UP monomer with [beta] -strands in blue and [alpha] -helices in green. BAU and phosphate are shown in stick representation bound at the active site. C atoms are colored green, N atoms blue, O atoms red and P atoms pink. (b) UP hexamer shown in ribbon representation with BAU (orange) and phosphate (red) shown bound at the active sites. Dimers with greater buried surface area are shown in similar colors. This figure was prepared with MOLSCRIPT (Kraulis, 1991 [Kraulis, P. J. (1991). J. Appl. Cryst. 24, 946-950.]-[bluearr.gif] ) and RASTER3D (Merritt & Bacon, 1997 [Merritt, E. A. & Bacon, D. J. (1997). Methods Enzymol. 277, 505-524.]-[bluearr.gif] ).		Figure 3. Figure 3 Schematic representation of the UP active site with bound (a) 5-fluorouridine and phosphate, (b) BAU and phosphate or (c) BBBA. Hydrogen bonds are shown in dashed lines. The active-site hydrophobic pocket is indicated by a solid line flanked by the participating residues.

Figures were selected by an automated process.

Literature references that cite this PDB file's key reference

PubMed id

Reference

20364833

D.Paul, S.E.O'Leary, K.Rajashankar, W.Bu, A.Toms, E.C.Settembre, J.M.Sanders, T.P.Begley, and S.E.Ealick (2010).
Glycal formation in crystals of uridine phosphorylase.

Biochemistry, 49, 3499-3509.

PDB codes:

3ku4 3kuk 3kvr 3kvv 3kvy

20070944

E.T.Larson, D.G.Mudeppa, J.R.Gillespie, N.Mueller, A.J.Napuli, J.A.Arif, J.Ross, T.L.Arakaki, A.Lauricella, G.Detitta, J.Luft, F.Zucker, C.L.Verlinde, E.Fan, W.C.Van Voorhis, F.S.Buckner, P.K.Rathod, W.G.Hol, and E.A.Merritt (2010).
The crystal structure and activity of a putative trypanosomal nucleoside phosphorylase reveal it to be a homodimeric uridine phosphorylase.

J Mol Biol, 396, 1244-1259.

PDB code:

3bje

20856879

T.P.Roosild, and S.Castronovo (2010).
Active site conformational dynamics in human uridine phosphorylase 1.

PLoS One, 5, e12741.

PDB code:

3nbq

19291308

T.P.Roosild, S.Castronovo, M.Fabbiani, and G.Pizzorno (2009).
Implications of the structure of human uridine phosphorylase 1 on the development of novel inhibitors for improving the therapeutic window of fluoropyrimidine chemotherapy.

BMC Struct Biol, 9, 14.

PDB codes:

3eue 3euf

The most recent references are shown first. Citation data come partly from CiteXplore and partly from an automated harvesting procedure. Note that this is likely to be only a partial list as not all journals are covered by either method. However, we are continually building up the citation data so more and more references will be included with time. Where a reference describes a PDB structure, the PDB codes are shown on the right.