8pba: Difference between revisions
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==Cryo-EM structure of Caenorhabditis elegans DPF-3 (apo)== | |||
<StructureSection load='8pba' size='340' side='right'caption='[[8pba]], [[Resolution|resolution]] 2.64Å' scene=''> | |||
== Structural highlights == | |||
<table><tr><td colspan='2'>[[8pba]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Caenorhabditis_elegans Caenorhabditis elegans]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=8PBA OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=8PBA FirstGlance]. <br> | |||
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">Electron Microscopy, [[Resolution|Resolution]] 2.64Å</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=8pba FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=8pba OCA], [https://pdbe.org/8pba PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=8pba RCSB], [https://www.ebi.ac.uk/pdbsum/8pba PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=8pba ProSAT]</span></td></tr> | |||
</table> | |||
== Function == | |||
[https://www.uniprot.org/uniprot/Q965K3_CAEEL Q965K3_CAEEL] | |||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
Substrate specificity determines protease functions in physiology and in clinical and biotechnological applications, yet quantitative cleavage information is often unavailable, biased, or limited to a small number of events. Here, we develop qPISA (quantitative Protease specificity Inference from Substrate Analysis) to study Dipeptidyl Peptidase Four (DPP4), a key regulator of blood glucose levels. We use mass spectrometry to quantify >40,000 peptides from a complex, commercially available peptide mixture. By analyzing changes in substrate levels quantitatively instead of focusing on qualitative product identification through a binary classifier, we can reveal cooperative interactions within DPP4's active pocket and derive a sequence motif that predicts activity quantitatively. qPISA distinguishes DPP4 from the related C. elegans DPF-3 (a DPP8/9-orthologue), and we relate the differences to the structural features of the two enzymes. We demonstrate that qPISA can direct protein engineering efforts like the stabilization of GLP-1, a key DPP4 substrate used in the treatment of diabetes and obesity. Thus, qPISA offers a versatile approach for profiling protease and especially exopeptidase specificity, facilitating insight into enzyme mechanisms and biotechnological and clinical applications. | |||
Deep quantification of substrate turnover defines protease subsite cooperativity.,Gudipati RK, Gaidatzis D, Seebacher J, Muehlhaeusser S, Kempf G, Cavadini S, Hess D, Soneson C, Grosshans H Mol Syst Biol. 2024 Dec;20(12):1303-1328. doi: 10.1038/s44320-024-00071-4. Epub , 2024 Oct 28. PMID:39468329<ref>PMID:39468329</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
[[Category: | </div> | ||
<div class="pdbe-citations 8pba" style="background-color:#fffaf0;"></div> | |||
== References == | |||
<references/> | |||
__TOC__ | |||
</StructureSection> | |||
[[Category: Caenorhabditis elegans]] | |||
[[Category: Large Structures]] | |||
[[Category: Cavadini S]] | |||
[[Category: Grosshans H]] | |||
[[Category: Gudipati RK]] | |||
[[Category: Kempf G]] | |||
Latest revision as of 06:29, 15 January 2025
Cryo-EM structure of Caenorhabditis elegans DPF-3 (apo)
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