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The | ==The crystal structure of GxGD membrane protease FlaK== | ||
<StructureSection load='3s0x' size='340' side='right'caption='[[3s0x]], [[Resolution|resolution]] 3.60Å' scene=''> | |||
== Structural highlights == | |||
<table><tr><td colspan='2'>[[3s0x]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Methanococcus_maripaludis Methanococcus maripaludis]. The August 2011 RCSB PDB [https://pdb.rcsb.org/pdb/static.do?p=education_discussion/molecule_of_the_month/index.html Molecule of the Month] feature on ''Rhomboid Protease GlpG'' by David Goodsell is [https://dx.doi.org/10.2210/rcsb_pdb/mom_2011_8 10.2210/rcsb_pdb/mom_2011_8]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3S0X OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3S0X 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]] 3.6Å</td></tr> | |||
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=MSE:SELENOMETHIONINE'>MSE</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=3s0x FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3s0x OCA], [https://pdbe.org/3s0x PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3s0x RCSB], [https://www.ebi.ac.uk/pdbsum/3s0x PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3s0x ProSAT]</span></td></tr> | |||
</table> | |||
== Function == | |||
[https://www.uniprot.org/uniprot/FLAK_METM6 FLAK_METM6] Cleaves the N-terminal leader peptide from preflagellins.<ref>PMID:21765428</ref> | |||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
The GXGD proteases are polytopic membrane proteins with catalytic activities against membrane-spanning substrates that require a pair of aspartyl residues. Representative members of the family include preflagellin peptidase, type 4 prepilin peptidase, presenilin and signal peptide peptidase. Many GXGD proteases are important in medicine. For example, type 4 prepilin peptidase may contribute to bacterial pathogenesis, and mutations in presenilin are associated with Alzheimer's disease. As yet, there is no atomic-resolution structure in this protease family. Here we report the crystal structure of FlaK, a preflagellin peptidase from Methanococcus maripaludis, solved at 3.6 A resolution. The structure contains six transmembrane helices. The GXGD motif and a short transmembrane helix, helix 4, are positioned at the centre, surrounded by other transmembrane helices. The crystal structure indicates that the protease must undergo conformational changes to bring the GXGD motif and a second essential aspartyl residue from transmembrane helix 1 into close proximity for catalysis. A comparison of the crystal structure with models of presenilin derived from biochemical analysis reveals three common transmembrane segments that are similarly arranged around the active site. This observation reinforces the idea that the prokaryotic and human proteases are evolutionarily related. The crystal structure presented here provides a framework for understanding the mechanism of the GXGD proteases, and may facilitate the rational design of inhibitors that target specific members of the family. | |||
The crystal structure of GXGD membrane protease FlaK.,Hu J, Xue Y, Lee S, Ha Y Nature. 2011 Jul 17;475(7357):528-31. doi: 10.1038/nature10218. PMID:21765428<ref>PMID:21765428</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
</div> | |||
<div class="pdbe-citations 3s0x" style="background-color:#fffaf0;"></div> | |||
== References == | |||
<references/> | |||
__TOC__ | |||
</StructureSection> | |||
[[Category: Large Structures]] | |||
[[Category: Methanococcus maripaludis]] | |||
[[Category: RCSB PDB Molecule of the Month]] | |||
[[Category: Rhomboid Protease GlpG]] | |||
[[Category: Ha Y]] | |||
[[Category: Hu J]] | |||
[[Category: Xue Y]] | |||