6d9s

The (p)ppGpp-bound crystal structure of HPRT (hypoxanthine phosphoribosyltransferase)

spinqualitylabelsall models 6d9s, resolution 2.10Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 6d9s is a 2 chain structure with sequence from Bacillus anthracis. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 2.105Å Ligands: G4P, MG, PEG Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function B9ZW32_BACAN Publication Abstract from PubMed The alarmone (p)ppGpp regulates diverse targets, yet its target specificity and evolution remain poorly understood. Here, we elucidate the mechanism by which basal (p)ppGpp inhibits the purine salvage enzyme HPRT by sharing a conserved motif with its substrate PRPP. Intriguingly, HPRT regulation by (p)ppGpp varies across organisms and correlates with HPRT oligomeric forms. (p)ppGpp-sensitive HPRT exists as a PRPP-bound dimer or an apo- and (p)ppGpp-bound tetramer, where a dimer-dimer interface triggers allosteric structural rearrangements to enhance (p)ppGpp inhibition. Loss of this oligomeric interface results in weakened (p)ppGpp regulation. Our results reveal an evolutionary principle whereby protein oligomerization allows evolutionary change to accumulate away from a conserved binding pocket to allosterically alter specificity of ligand interaction. This principle also explains how another (p)ppGpp target GMK is variably regulated across species. Since most ligands bind near protein interfaces, we propose that this principle extends to many other protein-ligand interactions. Evolution of (p)ppGpp-HPRT regulation through diversification of an allosteric oligomeric interaction.,Anderson BW, Liu K, Wolak C, Dubiel K, She F, Satyshur KA, Keck JL, Wang JD Elife. 2019 Sep 25;8. pii: 47534. doi: 10.7554/eLife.47534. PMID:31552824 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Phosphoribosyltransferase 3D structures

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