2Q8Y
Structural insight into the enzymatic mechanism of the phophothreonine lyase
Summary for 2Q8Y
| Entry DOI | 10.2210/pdb2q8y/pdb |
| Descriptor | 27.5 kDa virulence protein, Mitogen-activated protein kinase 7 (3 entities in total) |
| Functional Keywords | alpha/beta fold, lyase-transferase complex, lyase/transferase |
| Biological source | Salmonella enteritidis More |
| Cellular location | Cytoplasm: Q13164 |
| Total number of polymer chains | 2 |
| Total formula weight | 28934.28 |
| Authors | Zhu, Y.-Q.,Wang, D.-C.,Shao, F. (deposition date: 2007-06-12, release date: 2007-12-11, Last modification date: 2024-10-09) |
| Primary citation | Zhu, Y.,Li, H.,Long, C.,Hu, L.,Xu, H.,Liu, L.,Chen, S.,Wang, D.C.,Shao, F. Structural insights into the enzymatic mechanism of the pathogenic MAPK phosphothreonine lyase Mol.Cell, 28:899-913, 2007 Cited by PubMed Abstract: The OspF family of phosphothreonine lyase, including SpvC from Salmonella, irreversibly inactivates the dual-phosphorylated host MAPKs (pT-X-pY) through beta elimination. We determined crystal structures of SpvC and its complex with a phosphopeptide substrate. SpvC adopts a unique fold of alpha/beta type. The disordered N terminus harbors a canonical D motif for MAPK substrate docking. The enzyme-substrate complex structure indicates that recognition of the phosphotyrosine followed by insertion of the threonine phosphate into an arginine pocket places the phosphothreonine into the enzyme active site. This requires the conformational flexibility of pT-X-pY, which suggests that p38 (pT-G-pY) is likely the preferred physiological substrate. Structure-based biochemical and enzymatic analysis allows us to propose a general acid/base mechanism for beta elimination reaction catalyzed by the phosphothreonine lyase. The mechanism described here provides a structural understanding of MAPK inactivation by a family of pathogenic effectors conserved in plant and animal systems and may also open a new route for biological catalysis. PubMed: 18060821DOI: 10.1016/j.molcel.2007.11.011 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (2 Å) |
Structure validation
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