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| | ==Pre-cleavage Structure of the Autotransporter EspP - N1023A mutant== | | ==Pre-cleavage Structure of the Autotransporter EspP - N1023A mutant== |
| - | <StructureSection load='3slj' size='340' side='right' caption='[[3slj]], [[Resolution|resolution]] 2.48Å' scene=''> | + | <StructureSection load='3slj' size='340' side='right'caption='[[3slj]], [[Resolution|resolution]] 2.48Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[3slj]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Eco57 Eco57]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3SLJ OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3SLJ FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[3slj]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Escherichia_coli_O157:H7 Escherichia coli O157:H7]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3SLJ OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3SLJ FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=C8E:(HYDROXYETHYLOXY)TRI(ETHYLOXY)OCTANE'>C8E</scene></td></tr> | + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.481Å</td></tr> |
| - | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[3slo|3slo]], [[3slt|3slt]]</td></tr>
| + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=C8E:(HYDROXYETHYLOXY)TRI(ETHYLOXY)OCTANE'>C8E</scene></td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">ECO57PM78, espP, L7020 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=83334 ECO57])</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=3slj FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3slj OCA], [https://pdbe.org/3slj PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3slj RCSB], [https://www.ebi.ac.uk/pdbsum/3slj PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3slj ProSAT]</span></td></tr> |
| - | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3slj FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3slj OCA], [http://pdbe.org/3slj PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=3slj RCSB], [http://www.ebi.ac.uk/pdbsum/3slj PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=3slj ProSAT]</span></td></tr> | + | |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/ESPP_ECO57 ESPP_ECO57]] Serine protease capable of cleaving pepsin A and human coagulation factor V, which may contribute to the mucosal hemorrhage observed in hemorrhagic colitis.<ref>PMID:9194704</ref> <ref>PMID:15615856</ref> | + | [https://www.uniprot.org/uniprot/ESPP_ECO57 ESPP_ECO57] Serine protease capable of cleaving pepsin A and human coagulation factor V, which may contribute to the mucosal hemorrhage observed in hemorrhagic colitis.<ref>PMID:9194704</ref> <ref>PMID:15615856</ref> |
| - | <div style="background-color:#fffaf0;">
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| - | == Publication Abstract from PubMed ==
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| - | Autotransporters are secreted proteins produced by pathogenic Gram-negative bacteria. They consist of a membrane-embedded beta-domain and an extracellular passenger domain that is sometimes cleaved and released from the cell surface. We solved the structures of three noncleavable mutants of the autotransporter EspP to examine how it promotes asparagine cyclization to cleave its passenger. We found that cyclization is facilitated by multiple factors. The active-site asparagine is sterically constrained to conformations favorable for cyclization, while electrostatic interactions correctly orient the carboxamide group for nucleophilic attack. During molecular dynamics simulations, water molecules were observed to enter the active site and to form hydrogen bonds favorable for increasing the nucleophilicity of the active-site asparagine. When the activated asparagine attacks its main-chain carbonyl carbon, the resulting oxyanion is stabilized by a protonated glutamate. Upon cleavage, this proton could be transferred to the leaving amine group, helping overcome a significant energy barrier. Together, these findings provide insight into factors important for asparagine cyclization, a mechanism broadly used for protein cleavage.
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| - | Molecular Basis for the Activation of a Catalytic Asparagine Residue in a Self-Cleaving Bacterial Autotransporter.,Barnard TJ, Gumbart J, Peterson JH, Noinaj N, Easley NC, Dautin N, Kuszak AJ, Tajkhorshid E, Bernstein HD, Buchanan SK J Mol Biol. 2011 Nov 7. PMID:22094314<ref>PMID:22094314</ref>
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| - | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
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| - | </div>
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| - | <div class="pdbe-citations 3slj" style="background-color:#fffaf0;"></div>
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| | == References == | | == References == |
| | <references/> | | <references/> |
| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Eco57]] | + | [[Category: Escherichia coli O157:H7]] |
| - | [[Category: Barnard, T B]]
| + | [[Category: Large Structures]] |
| - | [[Category: Buchanan, S K]] | + | [[Category: Barnard TB]] |
| - | [[Category: Easley, N C]] | + | [[Category: Buchanan SK]] |
| - | [[Category: Kuszak, A J]] | + | [[Category: Easley NC]] |
| - | [[Category: Noinaj, N]] | + | [[Category: Kuszak AJ]] |
| - | [[Category: Asparagine cyclization]] | + | [[Category: Noinaj N]] |
| - | [[Category: Autocleavage]] | + | |
| - | [[Category: Beta barrel]]
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| - | [[Category: Membrane protein]]
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| - | [[Category: Protein transport]]
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