4QRH
Molecular mechanism and evolution of guanylate kinase regulation by (p)ppGpp
Summary for 4QRH
| Entry DOI | 10.2210/pdb4qrh/pdb |
| Related | 2J41 |
| Descriptor | Guanylate kinase, SULFATE ION, MAGNESIUM ION, ... (7 entities in total) |
| Functional Keywords | guanylate kinase, phosphotransferase, pppgpp, transferase |
| Biological source | Staphylococcus aureus USA300-ISMMS1 |
| Cellular location | Cytoplasm : W6E076 |
| Total number of polymer chains | 4 |
| Total formula weight | 100000.66 |
| Authors | Liu, K.,Krasny, K.,Myers, A.R.,Satyshur, K.A.,Keck, J.L.,Wnag, J.D. (deposition date: 2014-07-01, release date: 2015-02-25, Last modification date: 2024-11-06) |
| Primary citation | Liu, K.,Myers, A.R.,Pisithkul, T.,Claas, K.R.,Satyshur, K.A.,Amador-Noguez, D.,Keck, J.L.,Wang, J.D. Molecular Mechanism and Evolution of Guanylate Kinase Regulation by (p)ppGpp. Mol.Cell, 57:735-749, 2015 Cited by PubMed Abstract: 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. PubMed: 25661490DOI: 10.1016/j.molcel.2014.12.037 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (1.65 Å) |
Structure validation
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