1.0ZoBio - Drug Discovery Technologyhttps://zobio.com/onlineContent manager ~KBhttps://zobio.com/online/author/kasia/Mettl3/Mettl14 – An epitranscriptomic writer complex - ZoBio - Drug Discovery Technologyrich600338<blockquote class="wp-embedded-content" data-secret="ytsH7Jpmkb"><a href="https://zobio.com/online/cases/mettl3-mettl14-an-epitranscriptomic-writer-complex/">Mettl3/Mettl14 – An epitranscriptomic writer complex</a></blockquote><iframe sandbox="allow-scripts" security="restricted" src="https://zobio.com/online/cases/mettl3-mettl14-an-epitranscriptomic-writer-complex/embed/#?secret=ytsH7Jpmkb" width="600" height="338" title="“Mettl3/Mettl14 – An epitranscriptomic writer complex” — ZoBio - Drug Discovery Technology" data-secret="ytsH7Jpmkb" frameborder="0" marginwidth="0" marginheight="0" scrolling="no" class="wp-embedded-content"></iframe><script type="text/javascript">
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https://zobio.com/online/wp-content/uploads/2020/01/2651.jpg1200628Challenge Mettl3/Mettl14 is a large (90 kDa) heterodimeric “writer” complex that uses S-adenosyl methionine (SAM) as a cofactor. Identifying low affinity, validated fragment hits in the large amount of electron density derived from X-ray diffraction data was extremely difficult. Achievements We developed a highly efficient structure pipeline capable of determining up to 10 sub 2Å structures per month which has been the basis for elaborating fragment hits to cellular activity and beyond. Multiple chemotypes are promising, allowing for a robust hit-to-lead campaign.