2q8y
From Proteopedia
(Difference between revisions)
| (12 intermediate revisions not shown.) | |||
| Line 1: | Line 1: | ||
| - | [[Image:2q8y.jpg|left|200px]] | ||
| - | + | ==Structural insight into the enzymatic mechanism of the phophothreonine lyase== | |
| - | + | <StructureSection load='2q8y' size='340' side='right'caption='[[2q8y]], [[Resolution|resolution]] 2.00Å' scene=''> | |
| - | + | == Structural highlights == | |
| - | + | <table><tr><td colspan='2'>[[2q8y]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] and [https://en.wikipedia.org/wiki/Salmonella_enterica_subsp._enterica_serovar_Enteritidis Salmonella enterica subsp. enterica serovar Enteritidis]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2Q8Y OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2Q8Y FirstGlance]. <br> | |
| - | + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2Å</td></tr> | |
| - | + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=PTR:O-PHOSPHOTYROSINE'>PTR</scene>, <scene name='pdbligand=TPO:PHOSPHOTHREONINE'>TPO</scene></td></tr> | |
| - | + | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=2q8y FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2q8y OCA], [https://pdbe.org/2q8y PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2q8y RCSB], [https://www.ebi.ac.uk/pdbsum/2q8y PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2q8y ProSAT]</span></td></tr> | |
| - | | | + | </table> |
| - | + | == Function == | |
| - | + | [https://www.uniprot.org/uniprot/SPVC_SALEN SPVC_SALEN] Secreted effector that irreversibly inactivates host MAP kinases by catalyzing the dephosphorylation of the phosphothreonine residue in the pT-X-pY motif present in MAPKs, via a beta-elimination reaction leading to a dehydrobutyrine residue. | |
| - | + | <div style="background-color:#fffaf0;"> | |
| - | + | == Publication Abstract from PubMed == | |
| - | + | ||
| - | + | ||
| - | == | + | |
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. | 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. | ||
| - | + | Structural insights into the enzymatic mechanism of the pathogenic MAPK phosphothreonine lyase.,Zhu Y, Li H, Long C, Hu L, Xu H, Liu L, Chen S, Wang DC, Shao F Mol Cell. 2007 Dec 14;28(5):899-913. Epub 2007 Nov 29. PMID:18060821<ref>PMID:18060821</ref> | |
| - | + | ||
| - | + | ||
| - | + | ||
| - | Structural insights into the enzymatic mechanism of the pathogenic MAPK phosphothreonine lyase., Zhu Y, Li H, Long C, Hu L, Xu H, Liu L, Chen S, Wang DC, Shao F | + | |
| - | + | ||
| - | + | ||
| - | + | ||
| - | + | ||
| - | + | ||
| - | + | ||
| - | + | ||
| - | + | ||
| - | + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |
| + | </div> | ||
| + | <div class="pdbe-citations 2q8y" style="background-color:#fffaf0;"></div> | ||
| + | == References == | ||
| + | <references/> | ||
| + | __TOC__ | ||
| + | </StructureSection> | ||
| + | [[Category: Homo sapiens]] | ||
| + | [[Category: Large Structures]] | ||
| + | [[Category: Salmonella enterica subsp. enterica serovar Enteritidis]] | ||
| + | [[Category: Shao F]] | ||
| + | [[Category: Wang D-C]] | ||
| + | [[Category: Zhu Y-Q]] | ||
Current revision
Structural insight into the enzymatic mechanism of the phophothreonine lyase
| |||||||||||
