Mapping the Structural Path for Allosteric Inhibition of a Short-Form ATP Phosphoribosyltransferase by Histidine.

ABSTRACT: ATP phosphoribosyltransferase (ATPPRT) catalyzes the first step of histidine biosynthesis, being allosterically inhibited by the final product of the pathway. Allosteric inhibition of long-form ATPPRTs by histidine has been extensively studied, but inhibition of short-form ATPPRTs is poorly understood. Short-form ATPPRTs are hetero-octamers formed by four catalytic subunits (HisG_S) and four regulatory subunits (HisZ). HisG_S alone is catalytically active and insensitive to histidine. HisZ enhances catalysis by HisG_S in the absence of histidine but mediates allosteric inhibition in its presence. Here, steady-state and pre-steady-state kinetics establish that histidine is a noncompetitive inhibitor of short-form ATPPRT and that inhibition does not occur by dis

SUBMITTER: Thomson CM 

PROVIDER: S-EPMC6685669 | biostudies-literature | 2019 Jul

REPOSITORIES: biostudies-literature