5f5k: Difference between revisions
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==E.Coli GlpG Y205F mutant complexed with aldehyde inhibitor in DMPC/CHAPSO bicelle== | ==E.Coli GlpG Y205F mutant complexed with aldehyde inhibitor in DMPC/CHAPSO bicelle== | ||
<StructureSection load='5f5k' size='340' side='right' caption='[[5f5k]], [[Resolution|resolution]] 2.40Å' scene=''> | <StructureSection load='5f5k' size='340' side='right'caption='[[5f5k]], [[Resolution|resolution]] 2.40Å' scene=''> | ||
== Structural highlights == | == Structural highlights == | ||
<table><tr><td colspan='2'>[[5f5k]] is a 2 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5F5K OCA]. For a <b>guided tour on the structure components</b> use [http:// | <table><tr><td colspan='2'>[[5f5k]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/"bacillus_coli"_migula_1895 "bacillus coli" migula 1895]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5F5K OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=5F5K FirstGlance]. <br> | ||
</td></tr><tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=5XU:(2~{S})-2-AZANYLPROPANAL'>5XU</scene>, <scene name='pdbligand=ACE:ACETYL+GROUP'>ACE</scene></td></tr> | </td></tr><tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=5XU:(2~{S})-2-AZANYLPROPANAL'>5XU</scene>, <scene name='pdbligand=ACE:ACETYL+GROUP'>ACE</scene></td></tr> | ||
<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[5f5b|5f5b]], [[5f5d|5f5d]], [[5f5g|5f5g]], [[5f5j|5f5j]]</td></tr> | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[5f5b|5f5b]], [[5f5d|5f5d]], [[5f5g|5f5g]], [[5f5j|5f5j]]</td></tr> | ||
<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">glpG, SK83_00858 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=562 "Bacillus coli" Migula 1895])</td></tr> | |||
<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Rhomboid_protease Rhomboid protease], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.4.21.105 3.4.21.105] </span></td></tr> | <tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Rhomboid_protease Rhomboid protease], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.4.21.105 3.4.21.105] </span></td></tr> | ||
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http:// | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://proteopedia.org/fgij/fg.htm?mol=5f5k FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5f5k OCA], [http://pdbe.org/5f5k PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5f5k RCSB], [http://www.ebi.ac.uk/pdbsum/5f5k PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5f5k ProSAT]</span></td></tr> | ||
</table> | </table> | ||
== Function == | == Function == | ||
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</div> | </div> | ||
<div class="pdbe-citations 5f5k" style="background-color:#fffaf0;"></div> | <div class="pdbe-citations 5f5k" style="background-color:#fffaf0;"></div> | ||
==See Also== | |||
*[[Rhomboid protease|Rhomboid protease]] | |||
== References == | == References == | ||
<references/> | <references/> | ||
__TOC__ | __TOC__ | ||
</StructureSection> | </StructureSection> | ||
[[Category: Bacillus coli migula 1895]] | |||
[[Category: Large Structures]] | |||
[[Category: Rhomboid protease]] | [[Category: Rhomboid protease]] | ||
[[Category: Cho, S]] | [[Category: Cho, S]] | ||
Revision as of 11:00, 29 April 2020
E.Coli GlpG Y205F mutant complexed with aldehyde inhibitor in DMPC/CHAPSO bicelleE.Coli GlpG Y205F mutant complexed with aldehyde inhibitor in DMPC/CHAPSO bicelle
Structural highlights
Function[A0A0J2E248_ECOLX] Rhomboid-type serine protease that catalyzes intramembrane proteolysis.[HAMAP-Rule:MF_01594] Publication Abstract from PubMedIntramembrane proteases signal by releasing proteins from the membrane, but despite their importance, their enzymatic mechanisms remain obscure. We probed rhomboid proteases with reversible, mechanism-based inhibitors that allow precise kinetic analysis and faithfully mimic the transition state structurally. Unexpectedly, inhibition by peptide aldehydes is non-competitive, revealing that in the Michaelis complex, substrate does not contact the catalytic center. Structural analysis in a membrane revealed that all extracellular loops of rhomboid make stabilizing interactions with substrate, but mainly through backbone interactions, explaining rhomboid's broad sequence selectivity. At the catalytic site, the tetrahedral intermediate lies covalently attached to the catalytic serine alone, with the oxyanion stabilized by unusual tripartite interactions with the side chains of H150, N154, and the backbone of S201. We also visualized unexpected substrate-enzyme interactions at the non-essential P2/P3 residues. These "extra" interactions foster potent rhomboid inhibition in living cells, thereby opening avenues for rational design of selective rhomboid inhibitors. Crystal Structures and Inhibition Kinetics Reveal a Two-Stage Catalytic Mechanism with Drug Design Implications for Rhomboid Proteolysis.,Cho S, Dickey SW, Urban S Mol Cell. 2016 Feb 4;61(3):329-40. doi: 10.1016/j.molcel.2015.12.022. Epub 2016, Jan 21. PMID:26805573[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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