Biomaterial Database

Structure of the divalent cation.nucleotide complex at the active site of phosphoribosylpyrophosphate synthetase. 1980

K J Gibson, and R L Switzer

When Mg2+ was used as the activating cation, the phosphoribosylpyrophosphate synthetase (EC 2.7.6.1) of Salmonella typhimurium showed absolute specificity for the A(S) enantiomer of adenosine 5'-O-(1-thiotriphosphate), which gave a Km of 72 +/- 10 microM and a Vmax of 111 +/- 5 mumol/min/mg. The corresponding values for ATP were 46 +/- 3 microM and approximately 107 mumol/min/mg. Under the same conditions the B(R) isomer was a linearly competitive inhibitor (Ki = 54 +/- 11 microM) with respect to ATP. When Cd2+ replaced Mg2+, the two isomers reacted at comparable rates (Vmax (A)/Vmax (B) approximately equal to 0.8). This change in specificity suggests that the alpha-phosphate of ATP is liganded to a divalent cation during catalysis. Adenosine 5'-O-thiomonophosphate was 34-fold more effective as a product inhibitor when Cd2+ replaced Mg2+, while the effectiveness of AMP was not altered. This result suggests a divalent cation bridge between the enzyme and the alpha-phosphate of nucleotides. The results of these and previously published experiments enable us to propose a structure and stereochemical configuration for the divalent cation.ATP complex at the active site of phosphoribosylpyrophosphate synthetase.

UI	MeSH Term	Description	Entries
D007700	Kinetics	The rate dynamics in chemical or physical systems.
D008968	Molecular Conformation	The characteristic three-dimensional shape of a molecule.	Molecular Configuration,3D Molecular Structure,Configuration, Molecular,Molecular Structure, Three Dimensional,Three Dimensional Molecular Structure,3D Molecular Structures,Configurations, Molecular,Conformation, Molecular,Conformations, Molecular,Molecular Configurations,Molecular Conformations,Molecular Structure, 3D,Molecular Structures, 3D,Structure, 3D Molecular,Structures, 3D Molecular
D010770	Phosphotransferases	A rather large group of enzymes comprising not only those transferring phosphate but also diphosphate, nucleotidyl residues, and others. These have also been subdivided according to the acceptor group. (From Enzyme Nomenclature, 1992) EC 2.7.	Kinases,Phosphotransferase,Phosphotransferases, ATP,Transphosphorylase,Transphosphorylases,Kinase,ATP Phosphotransferases
D011485	Protein Binding	The process in which substances, either endogenous or exogenous, bind to proteins, peptides, enzymes, protein precursors, or allied compounds. Specific protein-binding measures are often used as assays in diagnostic assessments.	Plasma Protein Binding Capacity,Binding, Protein
D002413	Cations, Divalent	Positively charged atoms, radicals or groups of atoms with a valence of plus 2, which travel to the cathode or negative pole during electrolysis.	Divalent Cations
D000255	Adenosine Triphosphate	An adenine nucleotide containing three phosphate groups esterified to the sugar moiety. In addition to its crucial roles in metabolism adenosine triphosphate is a neurotransmitter.	ATP,Adenosine Triphosphate, Calcium Salt,Adenosine Triphosphate, Chromium Salt,Adenosine Triphosphate, Magnesium Salt,Adenosine Triphosphate, Manganese Salt,Adenylpyrophosphate,CaATP,CrATP,Manganese Adenosine Triphosphate,MgATP,MnATP,ATP-MgCl2,Adenosine Triphosphate, Chromium Ammonium Salt,Adenosine Triphosphate, Magnesium Chloride,Atriphos,Chromium Adenosine Triphosphate,Cr(H2O)4 ATP,Magnesium Adenosine Triphosphate,Striadyne,ATP MgCl2
D001665	Binding Sites	The parts of a macromolecule that directly participate in its specific combination with another molecule.	Combining Site,Binding Site,Combining Sites,Site, Binding,Site, Combining,Sites, Binding,Sites, Combining
D012268	Ribose-Phosphate Pyrophosphokinase	An enzyme that catalyzes the formation of phosphoribosyl pyrophosphate from ATP and ribose-5-phosphate. EC 2.7.6.1.	PRPP Synthetase,Phosphoribosyl Pyrophosphate Synthetase,5-Phospho-alpha-D-Ribose 1-Diphosphate Synthetase,PRibPP Synthetase,Ribosephosphate Pyrophosphokinase,1-Diphosphate Synthetase, 5-Phospho-alpha-D-Ribose,5 Phospho alpha D Ribose 1 Diphosphate Synthetase,Pyrophosphate Synthetase, Phosphoribosyl,Pyrophosphokinase, Ribose-Phosphate,Pyrophosphokinase, Ribosephosphate,Ribose Phosphate Pyrophosphokinase,Synthetase, 5-Phospho-alpha-D-Ribose 1-Diphosphate,Synthetase, PRPP,Synthetase, Phosphoribosyl Pyrophosphate
D012486	Salmonella typhimurium	A serotype of Salmonella enterica that is a frequent agent of Salmonella gastroenteritis in humans. It also causes PARATYPHOID FEVER.	Salmonella typhimurium LT2