1u1f: Difference between revisions

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Structure of e. coli uridine phosphorylase complexed to 5-(m-(benzyloxy)benzyl)acyclouridine (BBAU)

OverviewOverview

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.

About this StructureAbout this Structure

1U1F is a Single protein structure of sequence from Escherichia coli with , and as ligands. Active as Uridine phosphorylase, with EC number 2.4.2.3 Full crystallographic information is available from OCA.

ReferenceReference

Structural basis for inhibition of Escherichia coli uridine phosphorylase by 5-substituted acyclouridines., Bu W, Settembre EC, el Kouni MH, Ealick SE, Acta Crystallogr D Biol Crystallogr. 2005 Jul;61(Pt 7):863-72. Epub 2005, Jun 24. PMID:15983408

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-[[Image:1u1f.gif|left|200px]]<br /><applet load="1u1f" size="450" color="white" frame="true" align="right" spinBox="true"
+[[Image:1u1f.gif|left|200px]]<br /><applet load="1u1f" size="350" color="white" frame="true" align="right" spinBox="true"
 caption="1u1f, resolution 2.30&Aring;" />
 '''Structure of e. coli uridine phosphorylase complexed to 5-(m-(benzyloxy)benzyl)acyclouridine (BBAU)'''<br />
 ==Overview==
-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.
+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.
 ==About this Structure==
-U1F is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Escherichia_coli Escherichia coli] with PO4, K and 183 as [http://en.wikipedia.org/wiki/ligands ligands]. Active as [http://en.wikipedia.org/wiki/Uridine_phosphorylase Uridine phosphorylase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.4.2.3 2.4.2.3] Full crystallographic information is available from [http://ispc.weizmann.ac.il/oca-bin/ocashort?id=1U1F OCA].
+U1F is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Escherichia_coli Escherichia coli] with <scene name='pdbligand=PO4:'>PO4</scene>, <scene name='pdbligand=K:'>K</scene> and <scene name='pdbligand=183:'>183</scene> as [http://en.wikipedia.org/wiki/ligands ligands]. Active as [http://en.wikipedia.org/wiki/Uridine_phosphorylase Uridine phosphorylase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.4.2.3 2.4.2.3] Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1U1F OCA].
 ==Reference==
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 [[Category: Uridine phosphorylase]]
 [[Category: Bu, W.]]
-[[Category: Ealick, S.E.]]
+[[Category: Ealick, S E.]]
-[[Category: Settembre, E.C.]]
+[[Category: Settembre, E C.]]
 [[Category: 183]]
 [[Category: K]]
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 [[Category: pyrimidine nucleoside phosphorylase; uridine salvage; udp; 5-(m-(benzyloxy)benzyl)acyclouridine; bbau]]
-''Page seeded by [http://ispc.weizmann.ac.il/oca OCA ] on Wed Nov 21 03:46:31 2007''
+''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 15:19:35 2008''