7Z8U

Catalytic subunit HisG R56A mutant from Psychrobacter arcticus ATPPRT (HisGZ) in complex with ATP and PRPP

Summary for 7Z8U

• Entry DOI: 10.2210/pdb7z8u/pdb
• Descriptor: ATP phosphoribosyltransferase, 1-O-pyrophosphono-5-O-phosphono-alpha-D-ribofuranose, ADENOSINE-5'-TRIPHOSPHATE, ... (5 entities in total)
• Functional Keywords: atp, phosphoribosyltransferase, atpprt, prpp, hisg, hisgz, histidine, biosynthesis, allosteric, transferase
• Biological source: Psychrobacter arcticus
• Total number of polymer chains: 1
• Total formula weight: 26076.41

Authors

Alphey, M.S.,Fisher, G.,da Silva, R.G. (deposition date: 2022-03-18, release date: 2022-03-30, Last modification date: 2024-02-07)

Primary citation

Fisher, G.,Corbella, M.,Alphey, M.S.,Nicholson, J.,Read, B.J.,Kamerlin, S.C.L.,da Silva, R.G.
Allosteric rescue of catalytically impaired ATP phosphoribosyltransferase variants links protein dynamics to active-site electrostatic preorganisation.
Nat Commun, 13:7607-7607, 2022

PubMed Abstract: ATP phosphoribosyltransferase catalyses the first step of histidine biosynthesis and is controlled via a complex allosteric mechanism where the regulatory protein HisZ enhances catalysis by the catalytic protein HisG while mediating allosteric inhibition by histidine. Activation by HisZ was proposed to position HisG Arg56 to stabilise departure of the pyrophosphate leaving group. Here we report active-site mutants of HisG with impaired reaction chemistry which can be allosterically restored by HisZ despite the HisZ:HisG interface lying ~20 Å away from the active site. MD simulations indicate HisZ binding constrains the dynamics of HisG to favour a preorganised active site where both Arg56 and Arg32 are poised to stabilise leaving-group departure in WT-HisG. In the Arg56Ala-HisG mutant, HisZ modulates Arg32 dynamics so that it can partially compensate for the absence of Arg56. These results illustrate how remote protein-protein interactions translate into catalytic resilience by restoring damaged electrostatic preorganisation at the active site.

PubMed: 36494361
DOI: 10.1038/s41467-022-34960-9

Experimental method

X-RAY DIFFRACTION (2 Å)