Crystal Structure of ATP Phosphoribosyltransferase fromMycobacterium tuberculosis * Academic Article uri icon

abstract

  • The N-1-(5'-phosphoribosyl)-ATP transferase catalyzes the first step of the histidine biosynthetic pathway and is regulated by a feedback mechanism by the product histidine. The crystal structures of the N-1-(5'-phosphoribosyl)-ATP transferase from Mycobacterium tuberculosis in complex with inhibitor histidine and AMP has been determined to 1.8 A resolution and without ligands to 2.7 A resolution. The active enzyme exists primarily as a dimer, and the histidine-inhibited form is a hexamer. The structure represents a new fold for a phosphoribosyltransferase, consisting of three continuous domains. The inhibitor AMP binds in the active site cavity formed between the two catalytic domains. A model for the mechanism of allosteric inhibition has been derived from conformational differences between the AMP:His-bound and apo structures.

altmetric score

  • 6

author list (cited authors)

  • Cho, Y., Sharma, V., & Sacchettini, J. C.

citation count

  • 70

complete list of authors

  • Cho, Yoonsang||Sharma, Vivek||Sacchettini, James C

publication date

  • March 2003