8cxw: Difference between revisions
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== Structural highlights == | == Structural highlights == | ||
<table><tr><td colspan='2'>[[8cxw]] is a 9 chain structure with sequence from [https://en.wikipedia.org/wiki/Clostridioides_difficile Clostridioides difficile] and [https://en.wikipedia.org/wiki/Clostridioides_difficile_630 Clostridioides difficile 630]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=8CXW OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=8CXW FirstGlance]. <br> | <table><tr><td colspan='2'>[[8cxw]] is a 9 chain structure with sequence from [https://en.wikipedia.org/wiki/Clostridioides_difficile Clostridioides difficile] and [https://en.wikipedia.org/wiki/Clostridioides_difficile_630 Clostridioides difficile 630]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=8CXW OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=8CXW FirstGlance]. <br> | ||
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene>, <scene name='pdbligand=K:POTASSIUM+ION'>K</scene>, <scene name='pdbligand=Q8L:Piclidenoson'>Q8L</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]] 2.78Å</td></tr> | ||
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene>, <scene name='pdbligand=K:POTASSIUM+ION'>K</scene>, <scene name='pdbligand=Q8L:Piclidenoson'>Q8L</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=8cxw FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=8cxw OCA], [https://pdbe.org/8cxw PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=8cxw RCSB], [https://www.ebi.ac.uk/pdbsum/8cxw PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=8cxw 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=8cxw FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=8cxw OCA], [https://pdbe.org/8cxw PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=8cxw RCSB], [https://www.ebi.ac.uk/pdbsum/8cxw PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=8cxw ProSAT]</span></td></tr> | ||
</table> | </table> | ||
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</div> | </div> | ||
<div class="pdbe-citations 8cxw" style="background-color:#fffaf0;"></div> | <div class="pdbe-citations 8cxw" style="background-color:#fffaf0;"></div> | ||
==See Also== | |||
*[[DNA methyltransferase 3D structures|DNA methyltransferase 3D structures]] | |||
== References == | == References == | ||
<references/> | <references/> | ||
Latest revision as of 13:04, 25 October 2023
CamA Adenine Methyltransferase Complexed to Cognate Substrate DNA and Inhibitor MC4682 (Compound 164)CamA Adenine Methyltransferase Complexed to Cognate Substrate DNA and Inhibitor MC4682 (Compound 164)
Structural highlights
FunctionPublication Abstract from PubMedAntivirulence agents targeting endospore-transmitted Clostridioides difficile infections are urgently needed. C. difficile-specific DNA adenine methyltransferase (CamA) is required for efficient sporulation and affects persistence in the colon. The active site of CamA is conserved and closely resembles those of hundreds of related S-adenosyl-l-methionine (SAM)-dependent methyltransferases, which makes the design of selective inhibitors more challenging. We explored the solvent-exposed edge of the SAM adenosine moiety and systematically designed 42 analogs of adenosine carrying substituents at the C6-amino group (N6) of adenosine. We compare the inhibitory properties and binding affinity of these diverse compounds and present the crystal structures of CamA in complex with 14 of them in the presence of substrate DNA. The most potent of these inhibitors, compound 39 (IC(50) approximately 0.4 muM and K(D) approximately 0.2 muM), is selective for CamA against closely related bacterial and mammalian DNA and RNA adenine methyltransferases, protein lysine and arginine methyltransferases, and human adenosine receptors. Systematic Design of Adenosine Analogs as Inhibitors of a Clostridioides difficile-Specific DNA Adenine Methyltransferase Required for Normal Sporulation and Persistence.,Zhou J, Horton JR, Menna M, Fiorentino F, Ren R, Yu D, Hajian T, Vedadi M, Mazzoccanti G, Ciogli A, Weinhold E, Huben M, Blumenthal RM, Zhang X, Mai A, Rotili D, Cheng X J Med Chem. 2022 Dec 29. doi: 10.1021/acs.jmedchem.2c01789. PMID:36581322[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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