Marino, Marco and Deuss, Miriam and Svergun, Dmitri I. and Konarev, Petr V. and Sterner, Reinhard and Mayans, Olga (2006) Structural and Mutational Analysis of Substrate Complexation by Anthranilate Phosphoribosyltransferase from Sulfolobus solfataricus. The Journal of Biological Chemistry 281 (30), pp. 21410-21421.
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The metabolic synthesis and degradation of essential nucleotide compounds are primarily carried out by phosphoribosyltransferases (PRT) and nucleoside phosphorylases (NP), respectively. Despite the resemblance of their reactions, five classes of PRTs and NPs exist, where anthranilate PRT (AnPRT) constitutes the only evolutionary link between synthesis and degradation processes. We have characterized the active site of dimeric AnPRT from Sulfolobus solfataricus by elucidating crystal structures of the wild-type enzyme complexed to its two natural substrates anthranilate and 5-phosphoribosyl-1-pyrophosphate/Mg2+. These bind into two different domains within each protomer and are brought together during catalysis by rotational domain motions as shown by small angle x-ray scattering data. Steady-state kinetics of mutated AnPRT variants address the role of active site residues in binding and catalysis. Results allow the comparative analysis of PRT and pyrimidine NP families and expose related structural motifs involved in nucleotide/nucleoside recognition by these enzyme families.
|Date:||28 July 2006|
|Institutions:||Biology, Preclinical Medicine > Institut für Biochemie, Genetik und Mikrobiologie|
|Subjects:||500 Science > 570 Life sciences|
|Refereed:||Yes, this version has been refereed|
|Created at the University of Regensburg:||Unknown|
|Deposited On:||06 Dec 2006|
|Last Modified:||20 Jul 2011 20:48|