7Z6R
Psychrobacter arcticus ATPPRT (HisGZ) R56A mutant bound to ATP and PRPP
Summary for 7Z6R
| Entry DOI | 10.2210/pdb7z6r/pdb |
| Descriptor | ATP phosphoribosyltransferase regulatory subunit, ATP phosphoribosyltransferase, ADENOSINE-5'-TRIPHOSPHATE, ... (5 entities in total) |
| Functional Keywords | phosphoribosyltransferase, atpprt, prpp, hisgz, histidine, biosynthesis, allosteric, transferase |
| Biological source | Psychrobacter arcticus More |
| Total number of polymer chains | 4 |
| Total formula weight | 138362.28 |
| Authors | Alphey, M.S.,Fisher, G.,da Silva, R.G. (deposition date: 2022-03-14, release date: 2022-03-23, 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 Cited by 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: 36494361DOI: 10.1038/s41467-022-34960-9 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (2.55 Å) |
Structure validation
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