7ayq: Difference between revisions

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<StructureSection load='7ayq' size='340' side='right'caption='[[7ayq]], [[Resolution|resolution]] 2.45&Aring;' scene=''>
<StructureSection load='7ayq' size='340' side='right'caption='[[7ayq]], [[Resolution|resolution]] 2.45&Aring;' scene=''>
== Structural highlights ==
== Structural highlights ==
<table><tr><td colspan='2'>[[7ayq]] is a 2 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=7AYQ OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7AYQ FirstGlance]. <br>
<table><tr><td colspan='2'>Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7AYQ OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7AYQ 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]] 2.45&#8491;</td></tr>
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.45&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=PO4:PHOSPHATE+ION'>PO4</scene>, <scene name='pdbligand=S9Z:~{N}-[3-[4-[(4-bromophenyl)methyl]piperazin-1-yl]carbonylphenyl]-2-ethyl-2-methanoyl-butanamide'>S9Z</scene>, <scene name='pdbligand=TMO:TRIMETHYLAMINE+OXIDE'>TMO</scene></td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=PO4:PHOSPHATE+ION'>PO4</scene>, <scene name='pdbligand=S9Z:~{N}-[3-[4-[(4-bromophenyl)methyl]piperazin-1-yl]carbonylphenyl]-2-ethyl-2-methanoyl-butanamide'>S9Z</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=7ayq FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7ayq OCA], [https://pdbe.org/7ayq PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7ayq RCSB], [https://www.ebi.ac.uk/pdbsum/7ayq PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7ayq ProSAT]</span></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=7ayq FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7ayq OCA], [https://pdbe.org/7ayq PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7ayq RCSB], [https://www.ebi.ac.uk/pdbsum/7ayq PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7ayq ProSAT]</span></td></tr>
</table>
</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.
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>
From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 7ayq" style="background-color:#fffaf0;"></div>


==See Also==
==See Also==
*[[Dipeptidyl peptidase 3D structures|Dipeptidyl peptidase 3D structures]]
*[[Dipeptidyl peptidase 3D structures|Dipeptidyl peptidase 3D structures]]
== References ==
<references/>
__TOC__
__TOC__
</StructureSection>
</StructureSection>
[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Large Structures]]
[[Category: Huber R]]
[[Category: Huber R]]
[[Category: Ross B]]
[[Category: Ross B]]

Latest revision as of 11:35, 17 October 2024

Crystal structure of DPP8 in complex with a 4-oxo-b-lactam based inhibitor, B114Crystal structure of DPP8 in complex with a 4-oxo-b-lactam based inhibitor, B114

Structural highlights

Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:X-ray diffraction, Resolution 2.45Å
Ligands:, , ,
Resources:FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

See Also

7ayq, resolution 2.45Å

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