4qrh

Molecular mechanism and evolution of guanylate kinase regulation by (p)ppGpp

spinqualitylabelsall models 4qrh, resolution 1.65Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 4qrh is a 4 chain structure with sequence from Staphylococcus aureus USA300-ISMMS1. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 1.65Å Ligands: 0O2, EDO, K, MG, SO4 Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function A0A0J9X1Z9_STAAU Publication Abstract from PubMed The nucleotide (p)ppGpp mediates bacterial stress responses, but its targets and underlying mechanisms of action vary among bacterial species and remain incompletely understood. Here, we characterize the molecular interaction between (p)ppGpp and guanylate kinase (GMK), revealing the importance of this interaction in adaptation to starvation. Combining structural and kinetic analyses, we show that (p)ppGpp binds the GMK active site and competitively inhibits the enzyme. The (p)ppGpp-GMK interaction prevents the conversion of GMP to GDP, resulting in GMP accumulation upon amino acid downshift. Abolishing this interaction leads to excess (p)ppGpp and defective adaptation to amino acid starvation. A survey of GMKs from phylogenetically diverse bacteria shows that the (p)ppGpp-GMK interaction is conserved in members of Firmicutes, Actinobacteria, and Deinococcus-Thermus, but not in Proteobacteria, where (p)ppGpp regulates RNA polymerase (RNAP). We propose that GMK is an ancestral (p)ppGpp target and RNAP evolved more recently as a direct target in Proteobacteria. Molecular Mechanism and Evolution of Guanylate Kinase Regulation by (p)ppGpp.,Liu K, Myers AR, Pisithkul T, Claas KR, Satyshur KA, Amador-Noguez D, Keck JL, Wang JD Mol Cell. 2015 Feb 19;57(4):735-49. doi: 10.1016/j.molcel.2014.12.037. Epub 2015 , Feb 5. PMID:25661490 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Guanylate kinase 3D structures

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