View source for 6pj8


==Time-resolved structural snapshot of proteolysis by GlpG inside the membrane==
<StructureSection load='6pj8' size='340' side='right'caption='[[6pj8]], [[Resolution|resolution]] 2.40&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[6pj8]] 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=6PJ8 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6PJ8 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]] 2.4&#8491;</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=6pj8 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6pj8 OCA], [https://pdbe.org/6pj8 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6pj8 RCSB], [https://www.ebi.ac.uk/pdbsum/6pj8 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6pj8 ProSAT]</span></td></tr>
</table>
== Function ==
[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;">
== Publication Abstract from PubMed ==
Protein cleavage inside the cell membrane triggers various pathophysiological signaling pathways, but the mechanism of catalysis is poorly understood. We solved ten structures of the Escherichia coli rhomboid protease in a bicelle membrane undergoing time-resolved steps that encompass the entire proteolytic reaction on a transmembrane substrate and an aldehyde inhibitor. Extensive gate opening accompanied substrate, but not inhibitor, binding, revealing that substrates and inhibitors take different paths to the active site. Catalysis unexpectedly commenced with, and was guided through subsequent catalytic steps by, motions of an extracellular loop, with local contributions from active site residues. We even captured the elusive tetrahedral intermediate that is uncleaved but covalently attached to the catalytic serine, about which the substrate was forced to bend dramatically. This unexpectedly stable intermediate indicates rhomboid catalysis uses an unprecedented reaction coordinate that may involve mechanically stressing the peptide bond, and could be selectively targeted by inhibitors.

Ten catalytic snapshots of rhomboid intramembrane proteolysis from gate opening to peptide release.,Cho S, Baker RP, Ji M, Urban S Nat Struct Mol Biol. 2019 Sep 30. pii: 10.1038/s41594-019-0296-9. doi:, 10.1038/s41594-019-0296-9. PMID:31570873<ref>PMID:31570873</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 6pj8" style="background-color:#fffaf0;"></div>

==See Also==
*[[Rhomboid protease|Rhomboid protease]]
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Drosophila melanogaster]]
[[Category: Escherichia coli]]
[[Category: Large Structures]]
[[Category: Cho S]]
[[Category: Urban S]]