{"id":2879,"date":"2018-07-24T17:00:00","date_gmt":"2018-07-24T16:00:00","guid":{"rendered":"https:\/\/sites.dundee.ac.uk\/alessio-ciulli\/?p=2879"},"modified":"2024-01-11T17:07:15","modified_gmt":"2024-01-11T17:07:15","slug":"two-ligandable-pockets-on-the-surface-of-the-vhl-e3-ligase","status":"publish","type":"post","link":"https:\/\/sites.dundee.ac.uk\/alessio-ciulli\/2018\/07\/24\/two-ligandable-pockets-on-the-surface-of-the-vhl-e3-ligase\/","title":{"rendered":"Two ligandable pockets on the surface of the VHL E3 ligase"},"content":{"rendered":"<p><\/p>\n\n\n<p>Two ligandable pockets on the surface of the VHL E3 ligase are revealed in our new paper just out in J Med Chem<\/p>\n\n\n\n<ul class=\"wp-block-list\">\n<li>Fragment screening and Xray crystallographic soaking identified two novel pockets &#8211; one on VHL far from the HIF site, and one on adaptor subunit ElonginB &#8211; both of functional relevance<\/li>\n\n\n\n<li>Surprisingly we found no fragments bound at the Hydroxyproline site where VHL inhibitors and ligands for PROTACs bind<\/li>\n\n\n\n<li>The two new pockets were validated computationally using surface probing druggability techniques and solvent MD mapping, and identified other pockets found to bind solvent molecules crystallographically<\/li>\n\n\n\n<li>The identified sites and non-covalent interactions will guide the design of more potent ligands, which have potential as new E3 ligase binding handles for targeted protein degradation-<\/li>\n<\/ul>\n\n\n\n<p>Well done to Xavi and Inge!<\/p>\n\n\n\n<p><a href=\"https:\/\/pubs.acs.org\/doi\/10.1021\/acs.jmedchem.8b00842\">Read our paper Open Access<\/a>.<\/p>\n","protected":false},"excerpt":{"rendered":"<p>Two ligandable pockets on the surface of the VHL E3 ligase are revealed in our new paper just out in J Med Chem Well done to Xavi and Inge! Read our paper Open Access.<\/p>\n","protected":false},"author":1,"featured_media":0,"comment_status":"open","ping_status":"open","sticky":false,"template":"","format":"standard","meta":{"footnotes":""},"categories":[18,4],"tags":[],"class_list":["post-2879","post","type-post","status-publish","format-standard","hentry","category-18","category-news"],"blocksy_meta":[],"_links":{"self":[{"href":"https:\/\/sites.dundee.ac.uk\/alessio-ciulli\/wp-json\/wp\/v2\/posts\/2879","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/sites.dundee.ac.uk\/alessio-ciulli\/wp-json\/wp\/v2\/posts"}],"about":[{"href":"https:\/\/sites.dundee.ac.uk\/alessio-ciulli\/wp-json\/wp\/v2\/types\/post"}],"author":[{"embeddable":true,"href":"https:\/\/sites.dundee.ac.uk\/alessio-ciulli\/wp-json\/wp\/v2\/users\/1"}],"replies":[{"embeddable":true,"href":"https:\/\/sites.dundee.ac.uk\/alessio-ciulli\/wp-json\/wp\/v2\/comments?post=2879"}],"version-history":[{"count":0,"href":"https:\/\/sites.dundee.ac.uk\/alessio-ciulli\/wp-json\/wp\/v2\/posts\/2879\/revisions"}],"wp:attachment":[{"href":"https:\/\/sites.dundee.ac.uk\/alessio-ciulli\/wp-json\/wp\/v2\/media?parent=2879"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/sites.dundee.ac.uk\/alessio-ciulli\/wp-json\/wp\/v2\/categories?post=2879"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/sites.dundee.ac.uk\/alessio-ciulli\/wp-json\/wp\/v2\/tags?post=2879"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}