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8hu6
From Proteopedia
(Difference between revisions)
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== Structural highlights == | == Structural highlights == | ||
<table><tr><td colspan='2'>[[8hu6]] is a 4 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=8HU6 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=8HU6 FirstGlance]. <br> | <table><tr><td colspan='2'>[[8hu6]] is a 4 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=8HU6 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=8HU6 FirstGlance]. <br> | ||
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=AMP:ADENOSINE+MONOPHOSPHATE'>AMP</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></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]] 2.33Å</td></tr> |
| + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=AMP:ADENOSINE+MONOPHOSPHATE'>AMP</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</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=8hu6 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=8hu6 OCA], [https://pdbe.org/8hu6 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=8hu6 RCSB], [https://www.ebi.ac.uk/pdbsum/8hu6 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=8hu6 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=8hu6 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=8hu6 OCA], [https://pdbe.org/8hu6 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=8hu6 RCSB], [https://www.ebi.ac.uk/pdbsum/8hu6 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=8hu6 ProSAT]</span></td></tr> | ||
</table> | </table> | ||
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== Function == | == Function == | ||
[https://www.uniprot.org/uniprot/AMPD2_HUMAN AMPD2_HUMAN] AMP deaminase plays a critical role in energy metabolism. Catalyzes the deamination of AMP to IMP and plays an important role in the purine nucleotide cycle.<ref>PMID:23911318</ref> | [https://www.uniprot.org/uniprot/AMPD2_HUMAN AMPD2_HUMAN] AMP deaminase plays a critical role in energy metabolism. Catalyzes the deamination of AMP to IMP and plays an important role in the purine nucleotide cycle.<ref>PMID:23911318</ref> | ||
| + | <div style="background-color:#fffaf0;"> | ||
| + | == Publication Abstract from PubMed == | ||
| + | AMP deaminase 2 (AMPD2) has been thought to play an important role in energy homeostasis and immuno-oncology, while selective AMPD2 inhibitors are highly demanded to clarify the physiological function of AMPD2. In this report, we describe selective AMPD2 inhibitors inducing allosteric modulation. Based on hypothesis that compounds that exhibit increased inhibition by preincubation would cause conformational change of the enzyme, starting from HTS hit compound 4, we discovered compound 8 through the SAR study. From X-ray structural information of 8, this chemical series has a novel mechanism of action that changes the substrate pocket to prevent AMP from binding. Further elaboration of compound 8 led to the tool compound 21 which exhibited potent inhibitory activity of AMPD2 in ex vivo evaluation of mouse liver. | ||
| + | |||
| + | The discovery of 3,3-dimethyl-1,2,3,4-tetrahydroquinoxaline-1-carboxamides as AMPD2 inhibitors with a novel mechanism of action.,Kitao Y, Saito T, Watanabe S, Ohe Y, Takahashi K, Akaki T, Adachi T, Doi S, Yamanaka K, Murai Y, Oba M, Suzuki T Bioorg Med Chem Lett. 2023 Jan 15;80:129110. doi: 10.1016/j.bmcl.2022.129110. , Epub 2022 Dec 20. PMID:36563792<ref>PMID:36563792</ref> | ||
| + | |||
| + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | ||
| + | </div> | ||
| + | <div class="pdbe-citations 8hu6" style="background-color:#fffaf0;"></div> | ||
== References == | == References == | ||
<references/> | <references/> | ||
Current revision
AMP deaminase 2 in complex with AMP
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