Crystal structures of anthranilate phosphoribosyl-transferase from Saccharomyces cerevisiae

Anthranilate phosphoribosyltransferase (AnPRT) catalyzes the transfer of the phosphoribosyl group of 5'- phosphoribosyl-1'-pyrophosphate (PRPP) to anthranilate to form phosphoribosyl-anthranilate. Crystal structures of AnPRTs from bacteria and archaea have previously been determined; however, the structure of Saccharomyces cerevisiae AnPRT (ScAnPRT) still remains unsolved. Here, crystal structures of ScAnPRT in the apo form as well as in complex with its substrate PRPP and the substrate analogue 4-fluoroanthranilate (4FA) are presented. These structures demonstrate that ScAnPRT exhibits the conserved structural fold of type III phosphoribosyltransferase enzymes and shares the similar mode of substrate binding found across the AnPRT protein family. In addition, crystal structures of ScAnPRT mutants (ScAnPRT(Ser121Ala) and ScAnPRT(Gly141Asn)) were also determined. These structures suggested that the conserved residue Ser121 is critical for binding PRPP, while Gly141 is dispensable for binding 4FA. In summary, these structures improved the preliminary understanding of the substrate-binding mode of ScAnPRT and laid foundations for future research.

Automated summary

Crystal structures of Saccharomyces cerevisiae Anthranilate phosphoribosyltransferase (ScAnPRT) in apo form, bound with its substrate PRPP and substrate analogue 4-fluoroanthranilate (4FA), were determined. The structures show the conserved fold and substrate binding mode of type III phosphoribosyltransferase enzymes, with insights into the importance of specific residues for substrate binding. These structures enhance understanding of ScAnPRT substrate binding and lay the groundwork for future research.