View source for 4qnz


==Crystal structure of rhomboid intramembrane protease GlpG F146I in complex with peptide derived inhibitor Ac-FATA-cmk==
<StructureSection load='4qnz' size='340' side='right'caption='[[4qnz]], [[Resolution|resolution]] 2.55&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[4qnz]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Escherichia_coli_str._K-12_substr._MC4100 Escherichia coli str. K-12 substr. MC4100]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4QNZ OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4QNZ 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]] 2.55&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=0QE:CHLOROMETHANE'>0QE</scene>, <scene name='pdbligand=ACE:ACETYL+GROUP'>ACE</scene>, <scene name='pdbligand=BNG:B-NONYLGLUCOSIDE'>BNG</scene>, <scene name='pdbligand=CL:CHLORIDE+ION'>CL</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=4qnz FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4qnz OCA], [https://pdbe.org/4qnz PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4qnz RCSB], [https://www.ebi.ac.uk/pdbsum/4qnz PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4qnz ProSAT]</span></td></tr>
</table>
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
The mechanisms of intramembrane proteases are incompletely understood due to the lack of structural data on substrate complexes. To gain insight into substrate binding by rhomboid proteases, we have synthesised a series of novel peptidyl-chloromethylketone (CMK) inhibitors and analysed their interactions with Escherichia coli rhomboid GlpG enzymologically and structurally. We show that peptidyl-CMKs derived from the natural rhomboid substrate TatA from bacterium Providencia stuartii bind GlpG in a substrate-like manner, and their co-crystal structures with GlpG reveal the S1 to S4 subsites of the protease. The S1 subsite is prominent and merges into the 'water retention site', suggesting intimate interplay between substrate binding, specificity and catalysis. Unexpectedly, the S4 subsite is plastically formed by residues of the L1 loop, an important but hitherto enigmatic feature of the rhomboid fold. We propose that the homologous region of members of the wider rhomboid-like protein superfamily may have similar substrate or client-protein binding function. Finally, using molecular dynamics, we generate a model of the Michaelis complex of the substrate bound in the active site of GlpG.

Substrate binding and specificity of rhomboid intramembrane protease revealed by substrate-peptide complex structures.,Zoll S, Stanchev S, Began J, Skerle J, Lepsik M, Peclinovska L, Majer P, Strisovsky K EMBO J. 2014 Sep 12. pii: e201489367. PMID:25216680<ref>PMID:25216680</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 4qnz" style="background-color:#fffaf0;"></div>

==See Also==
*[[Rhomboid protease|Rhomboid protease]]
== References ==
<references/>
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</StructureSection>
[[Category: Escherichia coli str. K-12 substr. MC4100]]
[[Category: Large Structures]]
[[Category: Strisovsky K]]
[[Category: Zoll S]]