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| | <StructureSection load='5f5b' size='340' side='right'caption='[[5f5b]], [[Resolution|resolution]] 2.30Å' scene=''> | | <StructureSection load='5f5b' size='340' side='right'caption='[[5f5b]], [[Resolution|resolution]] 2.30Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[5f5b]] 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=5F5B OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=5F5B FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[5f5b]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Drosophila_melanogaster Drosophila melanogaster] and [https://en.wikipedia.org/wiki/Escherichia_coli Escherichia coli]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5F5B OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5F5B 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='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.3Å</td></tr> |
| - | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[2ic8|2ic8]], [[2irv|2irv]], [[5f5d|5f5d]], [[5f5g|5f5g]], [[5f5j|5f5j]], [[5f5k|5f5k]]</td></tr>
| + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=5XU:(2~{S})-2-AZANYLPROPANAL'>5XU</scene>, <scene name='pdbligand=ACE:ACETYL+GROUP'>ACE</scene></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='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=5f5b FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5f5b OCA], [https://pdbe.org/5f5b PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5f5b RCSB], [https://www.ebi.ac.uk/pdbsum/5f5b PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5f5b ProSAT]</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://proteopedia.org/fgij/fg.htm?mol=5f5b FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5f5b OCA], [http://pdbe.org/5f5b PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5f5b RCSB], [http://www.ebi.ac.uk/pdbsum/5f5b PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5f5b ProSAT]</span></td></tr> | + | |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/A0A0J2E248_ECOLX A0A0J2E248_ECOLX]] Rhomboid-type serine protease that catalyzes intramembrane proteolysis.[HAMAP-Rule:MF_01594] | + | [https://www.uniprot.org/uniprot/GLPG_ECOLI GLPG_ECOLI] Rhomboid-type serine protease that catalyzes intramembrane proteolysis.<ref>PMID:17099694</ref> <ref>PMID:16216077</ref> |
| | <div style="background-color:#fffaf0;"> | | <div style="background-color:#fffaf0;"> |
| | == Publication Abstract from PubMed == | | == Publication Abstract from PubMed == |
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| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Bacillus coli migula 1895]] | + | [[Category: Drosophila melanogaster]] |
| | + | [[Category: Escherichia coli]] |
| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| - | [[Category: Rhomboid protease]]
| + | [[Category: Cho S]] |
| - | [[Category: Cho, S]] | + | [[Category: Dickey SW]] |
| - | [[Category: Dickey, S W]] | + | [[Category: Urban S]] |
| - | [[Category: Urban, S]] | + | |
| - | [[Category: Aldehyde inhibitor]]
| + | |
| - | [[Category: Hydrolase-hydrolase inhibitor complex]]
| + | |
| - | [[Category: Hydrolase-inhibitor complex]]
| + | |
| - | [[Category: Membrane protease]]
| + | |
| - | [[Category: Rhomboid]]
| + | |
| Structural highlights
Function
GLPG_ECOLI Rhomboid-type serine protease that catalyzes intramembrane proteolysis.[1] [2]
Publication Abstract from PubMed
Intramembrane 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[3]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Wu Z, Yan N, Feng L, Oberstein A, Yan H, Baker RP, Gu L, Jeffrey PD, Urban S, Shi Y. Structural analysis of a rhomboid family intramembrane protease reveals a gating mechanism for substrate entry. Nat Struct Mol Biol. 2006 Dec;13(12):1084-91. Epub 2006 Nov 10. PMID:17099694 doi:10.1038/nsmb1179
- ↑ Maegawa S, Ito K, Akiyama Y. Proteolytic action of GlpG, a rhomboid protease in the Escherichia coli cytoplasmic membrane. Biochemistry. 2005 Oct 18;44(41):13543-52. PMID:16216077 doi:10.1021/bi051363k
- ↑ Cho S, Dickey SW, Urban S. Crystal Structures and Inhibition Kinetics Reveal a Two-Stage Catalytic Mechanism with Drug Design Implications for Rhomboid Proteolysis. Mol Cell. 2016 Feb 4;61(3):329-40. doi: 10.1016/j.molcel.2015.12.022. Epub 2016, Jan 21. PMID:26805573 doi:http://dx.doi.org/10.1016/j.molcel.2015.12.022
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