Crystal structure of ATP phosphoribosyltransferase from Mycobacterium tuberculosis.
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.
Cho
Yoonsang
Y
Department of Biochemistry and Biophysics, Texas A & M University, College Station 77843-2128, USA.
Sharma
Vivek
V
Sacchettini
James C
JC
D001276:ATP Phosphoribosyltransferase / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D000249:Adenosine Monophosphate / Q000378:metabolism; D020134:Catalytic Domain; D003001:Cloning, Molecular; D008958:Models, Molecular; D009169:Mycobacterium tuberculosis / Q000201:enzymology* / Q000235:genetics; D020836:Protein Structure, Quaternary
D000249:Adenosine Monophosphate; D001276:ATP Phosphoribosyltransferase