Psychrobacter arcticus ATPPRT (HisGZ) R56A mutant bound to ATP and PRPPPsychrobacter arcticus ATPPRT (HisGZ) R56A mutant bound to ATP and PRPP

Structural highlights

7z6r is a 4 chain structure with sequence from Psychrobacter arcticus. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Ligands:,
Resources:FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

HISZ_PSYA2 Required for the first step of histidine biosynthesis. May allow the feedback regulation of ATP phosphoribosyltransferase activity by histidine.[HAMAP-Rule:MF_00125]

Publication Abstract from PubMed

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(S) while mediating allosteric inhibition by histidine. Activation by HisZ was proposed to position HisG(S) Arg56 to stabilise departure of the pyrophosphate leaving group. Here we report active-site mutants of HisG(S) with impaired reaction chemistry which can be allosterically restored by HisZ despite the HisZ:HisG(S) interface lying ~20 A away from the active site. MD simulations indicate HisZ binding constrains the dynamics of HisG(S) to favour a preorganised active site where both Arg56 and Arg32 are poised to stabilise leaving-group departure in WT-HisG(S). In the Arg56Ala-HisG(S) 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.

Allosteric rescue of catalytically impaired ATP phosphoribosyltransferase variants links protein dynamics to active-site electrostatic preorganisation.,Fisher G, Corbella M, Alphey MS, Nicholson J, Read BJ, Kamerlin SCL, da Silva RG Nat Commun. 2022 Dec 9;13(1):7607. doi: 10.1038/s41467-022-34960-9. PMID:36494361[1]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

See Also

References

  1. Fisher G, Corbella M, Alphey MS, Nicholson J, Read BJ, Kamerlin SCL, da Silva RG. Allosteric rescue of catalytically impaired ATP phosphoribosyltransferase variants links protein dynamics to active-site electrostatic preorganisation. Nat Commun. 2022 Dec 9;13(1):7607. PMID:36494361 doi:10.1038/s41467-022-34960-9

7z6r, resolution 2.55Å

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