7a3j: Difference between revisions

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-'''Unreleased structure'''
-The entry 7a3j is ON HOLD
+==Crystal structure of DPP8 in complex with a 4-oxo-b-lactam based inhibitor, A272==
+<StructureSection load='7a3j' size='340' side='right'caption='[[7a3j]], [[Resolution|resolution]] 3.00&Aring;' scene=''>
+== Structural highlights ==
+<table><tr><td colspan='2'>[[7a3j]] is a 3 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7A3J OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7A3J 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&#8491;</td></tr>
+<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=QXK:2-ethyl-2-methanoyl-~{N}-[3-[[4-(naphthalen-1-ylmethyl)piperazin-1-yl]methyl]phenyl]butanamide'>QXK</scene>, <scene name='pdbligand=TMO:TRIMETHYLAMINE+OXIDE'>TMO</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=7a3j FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7a3j OCA], [https://pdbe.org/7a3j PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7a3j RCSB], [https://www.ebi.ac.uk/pdbsum/7a3j PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7a3j ProSAT]</span></td></tr>
+</table>
+== Function ==
+[https://www.uniprot.org/uniprot/DPP8_HUMAN DPP8_HUMAN] Dipeptidyl peptidase that cleaves off N-terminal dipeptides from proteins having a Pro or Ala residue at position 2. May play a role in T-cell activation and immune function.<ref>PMID:11012666</ref>
+<div style="background-color:#fffaf0;">
+== Publication Abstract from PubMed ==
+Dipeptidyl peptidases 8 and 9 (DPP8/9) have gathered interest as drug targets due to their important roles in biological processes like immunity and tumorigenesis. Elucidation of their distinct individual functions remains an ongoing task and could benefit from the availability of novel, chemically diverse and selective chemical tools. Here, we report the activity-based protein profiling (ABPP)-mediated discovery of 4-oxo-beta-lactams as potent, non-substrate-like nanomolar DPP8/9 inhibitors. X-ray crystallographic structures revealed different ligand binding modes for DPP8 and DPP9, including an unprecedented targeting of an extended S2' (eS2') subsite in DPP8. Biological assays confirmed inhibition at both target and cellular levels. Altogether, our integrated chemical proteomics and structure-guided small molecule design approach led to novel DPP8/9 inhibitors with alternative molecular inhibition mechanisms, delivering the highest selectivity index reported to date.
-Authors:
+Chemoproteomics-Enabled Identification of 4-Oxo-beta-Lactams as Inhibitors of Dipeptidyl Peptidases 8 and 9.,Carvalho LAR, Ross B, Fehr L, Bolgi O, Wohrle S, Lum KM, Podlesainski D, Vieira AC, Kiefersauer R, Felix R, Rodrigues T, Lucas SD, Gross O, Geiss-Friedlander R, Cravatt BF, Huber R, Kaiser M, Moreira R Angew Chem Int Ed Engl. 2022 Sep 11. doi: 10.1002/anie.202210498. PMID:36089535<ref>PMID:36089535</ref>
-Description:
+From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
-[[Category: Unreleased Structures]]
+</div>
+<div class="pdbe-citations 7a3j" style="background-color:#fffaf0;"></div>
+==See Also==
+*[[Dipeptidyl peptidase 3D structures|Dipeptidyl peptidase 3D structures]]
+== References ==
+<references/>
+__TOC__
+</StructureSection>
+[[Category: Homo sapiens]]
+[[Category: Large Structures]]
+[[Category: Huber R]]
+[[Category: Ross BH]]