2V4Y

THE STRUCTURE OF E. COLI UMP KINASE IN COMPLEX WITH ITS ALLOSTERIC REGULATOR GTP

Summary for 2V4Y

• Entry DOI: 10.2210/pdb2v4y/pdb
• Related: 2BND 2BNE 2BNF
• Descriptor: URIDYLATE KINASE, GUANOSINE-5'-TRIPHOSPHATE (3 entities in total)
• Functional Keywords: nucleotide-binding, pyrimidine biosynthesis, transferase, atp-binding, allosteric enzyme, gtp, kinase, allostery, nmp kinase
• Biological source: ESCHERICHIA COLI
• Cellular location: Cytoplasm: P0A7E9
• Total number of polymer chains: 6
• Total formula weight: 162273.82

Authors

Meyer, P.,Evrin, C.,Briozzo, P.,Joly, N.,Barzu, O.,Gilles, A.M. (deposition date: 2008-09-30, release date: 2008-10-21, Last modification date: 2023-12-13)

Primary citation

Meyer, P.,Evrin, C.,Briozzo, P.,Joly, N.,Barzu, O.,Gilles, A.M.
Structural and Functional Characterization of Escherichia Coli Ump Kinase in Complex with its Allosteric Regulator GTP.
J.Biol.Chem., 283:36011-, 2008

PubMed Abstract: Bacterial UMP kinases are essential enzymes involved in the multistep synthesis of UTP. They are hexamers regulated by GTP (allosteric activator) and UTP (inhibitor). We describe here the 2.8 angstroms crystal structure of Escherichia coli UMP kinase bound to GTP. The GTP-binding site, situated at 15 angstroms from the UMP-binding site and at 24 angstroms from the ATP-binding site, is delineated by two contiguous dimers. The overall structure, as compared with those bound to UMP, UDP, or UTP, shows a rearrangement of its quaternary structure: GTP induces an 11 degrees opening of the UMP kinase dimer, resulting in a tighter dimer-dimer interaction. A nucleotide-free UMP kinase dimer has an intermediate opening. Superposition of our structure with that of archaeal UMP kinases, which are also hexamers, shows that a loop appears to hamper any GTP binding in archeal enzymes. This would explain the absence of activating effect of GTP on this group of UMP kinases. Among GTP-binding residues, the Asp-93 is the most conserved in bacterial UMP kinases. In the previously published structures of E. coli UMP kinase, this residue was shown to be involved in hydrogen bonds between the subunits of a dimer. Its substitution by an alanine decreases the cooperativity for UTP binding and suppresses the reversal by GTP of UTP inhibition. This demonstrates that the previously described mutual exclusion of these two nucleotides is mediated by Asp-93.

PubMed: 18945668
DOI: 10.1074/JBC.M802614200

Experimental method

X-RAY DIFFRACTION (2.8 Å)