2bnd: Difference between revisions

Revision as of 20:31, 3 May 2008

THE STRUCTURE OF E.COLI UMP KINASE IN COMPLEX WITH UDP

OverviewOverview

Bacterial UMP kinases are essential enzymes involved in the multistep synthesis of nucleoside triphosphates. They are hexamers regulated by the allosteric activator GTP and inhibited by UTP. We solved the crystal structure of Escherichia coli UMP kinase bound to the UMP substrate (2.3 A resolution), the UDP product (2.6 A), or UTP (2.45 A). The monomer fold, unrelated to that of other nucleoside monophosphate kinases, belongs to the carbamate kinase-like superfamily. However, the phosphate acceptor binding cleft and subunit assembly are characteristic of UMP kinase. Interactions with UMP explain the high specificity for this natural substrate. UTP, previously described as an allosteric inhibitor, was unexpectedly found in the phosphate acceptor site, suggesting that it acts as a competitive inhibitor. Site-directed mutagenesis of residues Thr-138 and Asn-140, involved in both uracil recognition and active site interaction within the hexamer, decreased the activation by GTP and inhibition by UTP. These experiments suggest a cross-talk mechanism between enzyme subunits involved in cooperative binding at the phosphate acceptor site and in allosteric regulation by GTP. As bacterial UMP kinases have no counterpart in eukaryotes, the information provided here could help the design of new antibiotics.

About this StructureAbout this Structure

2BND is a Single protein structure of sequence from Escherichia coli. Full crystallographic information is available from OCA.

ReferenceReference

Structure of Escherichia coli UMP kinase differs from that of other nucleoside monophosphate kinases and sheds new light on enzyme regulation., Briozzo P, Evrin C, Meyer P, Assairi L, Joly N, Barzu O, Gilles AM, J Biol Chem. 2005 Jul 8;280(27):25533-40. Epub 2005 Apr 27. PMID:15857829 Page seeded by OCA on Sat May 3 20:31:37 2008

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OCA

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 [[Image:2bnd.gif|left|200px]]
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 '''THE STRUCTURE OF E.COLI UMP KINASE IN COMPLEX WITH UDP'''
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 [[Category: Joly, N.]]
 [[Category: Meyer, P.]]
-[[Category: nucleoside monophosphate kinase]]
+[[Category: Nucleoside monophosphate kinase]]
-[[Category: pyrimidine biosynthesis]]
+[[Category: Pyrimidine biosynthesis]]
-[[Category: transferase]]
+[[Category: Transferase]]
+''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sat May  3 20:31:37 2008''
-''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Mon Mar 31 02:08:54 2008''