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| | ==Crystal structure of HhaI DNA methyltransferase in APO form== | | ==Crystal structure of HhaI DNA methyltransferase in APO form== |
| - | <StructureSection load='5lod' size='340' side='right' caption='[[5lod]], [[Resolution|resolution]] 1.90Å' scene=''> | + | <StructureSection load='5lod' size='340' side='right'caption='[[5lod]], [[Resolution|resolution]] 1.90Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[5lod]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Atcc_10014 Atcc 10014]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5LOD OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5LOD FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[5lod]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Haemophilus_parahaemolyticus Haemophilus parahaemolyticus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5LOD OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5LOD FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=SO4:SULFATE+ION'>SO4</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]] 1.9Å</td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">hhaIM ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=735 ATCC 10014])</td></tr>
| + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></td></tr> |
| - | <tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/DNA_(cytosine-5-)-methyltransferase DNA (cytosine-5-)-methyltransferase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.1.1.37 2.1.1.37] </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=5lod FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5lod OCA], [https://pdbe.org/5lod PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5lod RCSB], [https://www.ebi.ac.uk/pdbsum/5lod PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5lod ProSAT]</span></td></tr> |
| - | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5lod FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5lod OCA], [http://pdbe.org/5lod PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5lod RCSB], [http://www.ebi.ac.uk/pdbsum/5lod PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5lod ProSAT]</span></td></tr> | + | |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/MTH1_HAEPH MTH1_HAEPH]] This methylase recognizes the double-stranded sequence GCGC, causes specific methylation on C-2 on both strands, and protects the DNA from cleavage by the HhaI endonuclease. | + | [https://www.uniprot.org/uniprot/MTH1_HAEPH MTH1_HAEPH] This methylase recognizes the double-stranded sequence GCGC, causes specific methylation on C-2 on both strands, and protects the DNA from cleavage by the HhaI endonuclease. |
| | <div style="background-color:#fffaf0;"> | | <div style="background-color:#fffaf0;"> |
| | == Publication Abstract from PubMed == | | == Publication Abstract from PubMed == |
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| | </div> | | </div> |
| | <div class="pdbe-citations 5lod" style="background-color:#fffaf0;"></div> | | <div class="pdbe-citations 5lod" style="background-color:#fffaf0;"></div> |
| | + | |
| | + | ==See Also== |
| | + | *[[DNA methyltransferase 3D structures|DNA methyltransferase 3D structures]] |
| | == References == | | == References == |
| | <references/> | | <references/> |
| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Atcc 10014]] | + | [[Category: Haemophilus parahaemolyticus]] |
| - | [[Category: Rondelet, G]] | + | [[Category: Large Structures]] |
| - | [[Category: Wouters, J]] | + | [[Category: Rondelet G]] |
| - | [[Category: Apo form]] | + | [[Category: Wouters J]] |
| - | [[Category: C5-methylcytosine]]
| + | |
| - | [[Category: Dna methyltransferase]]
| + | |
| - | [[Category: M hhai]]
| + | |
| - | [[Category: Transferase]]
| + | |
| Structural highlights
Function
MTH1_HAEPH This methylase recognizes the double-stranded sequence GCGC, causes specific methylation on C-2 on both strands, and protects the DNA from cleavage by the HhaI endonuclease.
Publication Abstract from PubMed
AIM: DNA methyltransferases (DNMTs) are important drug targets for epigenetic therapy of cancer. Nowadays, non-nucleoside DNMT inhibitors are in development to address high toxicity of nucleoside analogs. However, these compounds still have low activity in cancer cells and mode of action of these compounds remains unclear. MATERIALS & METHODS: In this work, we studied maleimide derivatives of RG108 by biochemical, structural and computational approaches to highlight their inhibition mechanism on DNMTs. RESULTS: Findings demonstrated a correlation between cytotoxicity on mesothelioma cells of these compounds and their inhibitory potency against DNMTs. Noncovalent and covalent docking studies, supported by crystallographic (apo structure of M.HhaI) and differential scanning fluorimetry assays, provided detailed insights into their mode of action and revealed essential residues for the stabilization of such compounds inside DNMTs. [Formula: see text].
Inhibition studies of DNA methyltransferases by maleimide derivatives of RG108 as non-nucleoside inhibitors.,Rondelet G, Fleury L, Faux C, Masson V, Dubois J, Arimondo PB, Willems L, Wouters J Future Med Chem. 2017 Aug 10. doi: 10.4155/fmc-2017-0074. PMID:28795598[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Rondelet G, Fleury L, Faux C, Masson V, Dubois J, Arimondo PB, Willems L, Wouters J. Inhibition studies of DNA methyltransferases by maleimide derivatives of RG108 as non-nucleoside inhibitors. Future Med Chem. 2017 Aug 10. doi: 10.4155/fmc-2017-0074. PMID:28795598 doi:http://dx.doi.org/10.4155/fmc-2017-0074
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