{"id":892,"date":"2026-04-15T13:09:54","date_gmt":"2026-04-15T13:09:54","guid":{"rendered":"https:\/\/citations.tools.bio-logic.fr\/?p=892"},"modified":"2026-04-15T13:09:54","modified_gmt":"2026-04-15T13:09:54","slug":"active-site-coupling-in-plasmodium-falciparum-gmp-synthetase-is-triggered-by-domain-rotation","status":"publish","type":"post","link":"https:\/\/citations.tools.bio-logic.fr\/?p=892","title":{"rendered":"Active site coupling in Plasmodium falciparum GMP synthetase is triggered by domain rotation"},"content":{"rendered":"<h4>DOI:<\/h4>\n<p><a href=\"https:\/\/doi.org\/10.1038\/ncomms9930\" target=\"_blank\" rel=\"noopener\">10.1038\/ncomms9930<\/a><\/p>\n<h4>Authors:<\/h4>\n<p>Lionel Ballut, S\u00e9bastien Violot, Santosh Shivakumaraswamy, Lakshmi Prasoona Thota, M Sathya, Jyothirmai Kunala, Bauke W. Dijkstra, Rapha\u00ebl Terreux, Richard Haser, Hemalatha Balaram, N. Aghajari<\/p>\n<h4>Abstract:<\/h4>\n<p>Abstract GMP synthetase (GMPS), a key enzyme in the purine biosynthetic pathway performs catalysis through a coordinated process across two catalytic pockets for which the mechanism remains unclear. Crystal structures of Plasmodium falciparum GMPS in conjunction with mutational and enzyme kinetic studies reported here provide evidence that an 85\u00b0 rotation of the GATase domain is required for ammonia channelling and thus for the catalytic activity of this two-domain enzyme. We suggest that conformational changes in helix 371\u2013375 holding catalytic residues and in loop 376\u2013401 along the rotation trajectory trigger the different steps of catalysis, and establish the central role of Glu374 in allostery and inter-domain crosstalk. These studies reveal the mechanism of domain rotation and inter-domain communication, providing a molecular framework for the function of all single polypeptide GMPSs and form a solid basis for rational drug design targeting this therapeutically important enzyme.<\/p>\n","protected":false},"excerpt":{"rendered":"<p>DOI: 10.1038\/ncomms9930 Authors: Lionel Ballut, S\u00e9bastien Violot, Santosh Shivakumaraswamy, Lakshmi Prasoona Thota, M Sathya, Jyothirmai Kunala, Bauke W. Dijkstra, Rapha\u00ebl Terreux, Richard Haser, Hemalatha Balaram, N. Aghajari Abstract: Abstract GMP synthetase (GMPS), a key enzyme in the purine biosynthetic pathway performs catalysis through a coordinated process across two catalytic pockets for which the mechanism remains [&hellip;]<\/p>\n","protected":false},"author":1,"featured_media":0,"comment_status":"open","ping_status":"open","sticky":false,"template":"","format":"standard","meta":{"footnotes":""},"categories":[18],"tags":[],"class_list":["post-892","post","type-post","status-publish","format-standard","hentry","category-mos200"],"_links":{"self":[{"href":"https:\/\/citations.tools.bio-logic.fr\/index.php?rest_route=\/wp\/v2\/posts\/892","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/citations.tools.bio-logic.fr\/index.php?rest_route=\/wp\/v2\/posts"}],"about":[{"href":"https:\/\/citations.tools.bio-logic.fr\/index.php?rest_route=\/wp\/v2\/types\/post"}],"author":[{"embeddable":true,"href":"https:\/\/citations.tools.bio-logic.fr\/index.php?rest_route=\/wp\/v2\/users\/1"}],"replies":[{"embeddable":true,"href":"https:\/\/citations.tools.bio-logic.fr\/index.php?rest_route=%2Fwp%2Fv2%2Fcomments&post=892"}],"version-history":[{"count":0,"href":"https:\/\/citations.tools.bio-logic.fr\/index.php?rest_route=\/wp\/v2\/posts\/892\/revisions"}],"wp:attachment":[{"href":"https:\/\/citations.tools.bio-logic.fr\/index.php?rest_route=%2Fwp%2Fv2%2Fmedia&parent=892"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/citations.tools.bio-logic.fr\/index.php?rest_route=%2Fwp%2Fv2%2Fcategories&post=892"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/citations.tools.bio-logic.fr\/index.php?rest_route=%2Fwp%2Fv2%2Ftags&post=892"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}