Fig. 5: Differential modes of binding of ATP, GTP, and ppGpp to the CBS domain of MsmIMPDH impact the mobility of the hinge regions.
From: Deciphering the allosteric regulation of mycobacterial inosine-5′-monophosphate dehydrogenase
a ATP binds at Site 2 with the base in anti conformation relative to the ribose. b The GTP molecule binds with the base in syn conformation. The other nucleotide is shown as thin lines in the background for comparison of a and b. The contacts with Arg108 and Lys222 (in gold) are depicted by grey dotted lines; each number indicates the distance in Å. c The ppGpp molecule binds at a separate binding site in the CBS domain. d The hinge regions are flexible in the case of ATP binding (in gold), while the GTP locks the hinges in a fixed position (in grey). The side chains of Arg108 and Lys222 are depicted as sticks. e The mutation of Arg108A and Lys222A strongly reduces the inhibition of MsmIMPDH by ppGpp and GTP. NAD+ and IMP substrates were fixed at concentrations of 2 mM and 100 µM, respectively; ATP was fixed at 500 µM. The relative velocity value was calculated as the ratio of the initial velocity of the reaction to the control reaction of the corresponding enzyme (n = 3). Data are presented as mean values with error bars representing the SD.
