{"id":2484,"date":"2023-12-29T09:00:28","date_gmt":"2023-12-29T07:00:28","guid":{"rendered":"https:\/\/webs.uab.cat\/molbiomed\/2023\/12\/29\/new-paper-on-acs-catalysis\/"},"modified":"2024-02-27T16:33:26","modified_gmt":"2024-02-27T14:33:26","slug":"new-paper-on-acs-catalysis","status":"publish","type":"post","link":"https:\/\/webs.uab.cat\/molbiomed\/en\/2023\/12\/29\/new-paper-on-acs-catalysis\/","title":{"rendered":"New Paper on ACS Catalysis"},"content":{"rendered":"\n<p class=\"has-text-align-center has-accent-color has-text-color has-normal-font-size\"><strong>Theoretical Study of the Arachidonic Acid Conversion into Leukotriene A<sub>4<\/sub> Catalyzed by Human 5-Lipoxygenase: Hydroperoxidation and Epoxidation Mechanisms and Arachidonic Acid Active Site Access<\/strong><\/p>\n\n<p class=\"has-text-align-center\">Alejandro Cruz, \u00c0ngels Gonz\u00e1lez-Lafont, Jos\u00e9 M. Lluch<\/p>\n\n<p>Inflammation is at the base of many different diseases. Leukotrienes (LTs) are pro-inflammatory mediators derived from arachidonic acid (AA), which play significant roles in acute inflammation. Lipoxins are specialized pro-resolving mediators (SPMs), also formed from AA, that promote the resolution of acute inflammation. However, if resolution fails, chronic inflammatory processes might develop. The enzyme human-5-lipoxygenase (5-LOX) catalyzes the biosynthesis of leukotriene named LTA<sub>4<\/sub> but also intervenes in the formation of the lipoxin LXA<sub>4<\/sub>. These two biological functions have made the 5-LOX isoform a current target for pharmaceutical investigations in several inflammatory-based diseases searching for inhibitors that block the leukotriene reaction pathway but not lipoxin\u2019s formation. However, the development of those selective inhibitors has been hampered by the lack of a crystal structure of human 5-LOX. In this work, we have built a complete solvated model of the human-5-LOX: AA Michaelis complex using, as initial coordinates, the human 5-LOX structure from the AlphaFold protein structure database. We aim to analyze at the molecular level the overall catalytic mechanism of 5-LOX that first converts AA into 5(<em>S<\/em>)-HpETE through a hydroperoxidation reaction and, second, transforms this hydroperoxide into LTA<sub>4<\/sub> following an epoxidation process. Methodologically, we have performed molecular dynamics simulations and quantum mechanics\/molecular mechanics calculations. The free energy profiles for AA entrance into the 5-LOX\u2019s binding cavity have been calculated by steered molecular dynamics. This detailed molecular information can explain human-5-LOX\u2019s in vitro activity (without the presence of the membrane-embedded 5-lipoxygenase-activating protein) and help to design selective inhibitors favoring inflammation resolution.<\/p>\n\n<figure class=\"wp-block-image size-full\"><img loading=\"lazy\" decoding=\"async\" width=\"997\" height=\"547\" src=\"https:\/\/webs.uab.cat\/molbiomed\/wp-content\/uploads\/sites\/355\/2024\/01\/acs_dec23.jpeg\" alt=\"\" class=\"wp-image-2305\" srcset=\"https:\/\/webs.uab.cat\/molbiomed\/wp-content\/uploads\/sites\/355\/2024\/01\/acs_dec23.jpeg 997w, https:\/\/webs.uab.cat\/molbiomed\/wp-content\/uploads\/sites\/355\/2024\/01\/acs_dec23-300x165.jpeg 300w, https:\/\/webs.uab.cat\/molbiomed\/wp-content\/uploads\/sites\/355\/2024\/01\/acs_dec23-768x421.jpeg 768w\" sizes=\"auto, (max-width: 997px) 100vw, 997px\" \/><\/figure>\n","protected":false},"excerpt":{"rendered":"<p>Theoretical Study of the Arachidonic Acid Conversion into Leukotriene A4 Catalyzed by Human 5-Lipoxygenase: Hydroperoxidation and Epoxidation Mechanisms and Arachidonic Acid Active Site Access Alejandro Cruz, \u00c0ngels Gonz\u00e1lez-Lafont, Jos\u00e9 M. Lluch Inflammation is at the base of many different diseases. Leukotrienes (LTs) are pro-inflammatory mediators derived from arachidonic acid (AA), which play significant roles in [&hellip;]<\/p>\n","protected":false},"author":2580,"featured_media":0,"comment_status":"closed","ping_status":"closed","sticky":false,"template":"","format":"standard","meta":{"footnotes":""},"categories":[94,130,132],"tags":[],"class_list":["post-2484","post","type-post","status-publish","format-standard","hentry","category-lipoxygenases","category-molecular-dynamics","category-qm-mm-en"],"_links":{"self":[{"href":"https:\/\/webs.uab.cat\/molbiomed\/en\/wp-json\/wp\/v2\/posts\/2484","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/webs.uab.cat\/molbiomed\/en\/wp-json\/wp\/v2\/posts"}],"about":[{"href":"https:\/\/webs.uab.cat\/molbiomed\/en\/wp-json\/wp\/v2\/types\/post"}],"author":[{"embeddable":true,"href":"https:\/\/webs.uab.cat\/molbiomed\/en\/wp-json\/wp\/v2\/users\/2580"}],"replies":[{"embeddable":true,"href":"https:\/\/webs.uab.cat\/molbiomed\/en\/wp-json\/wp\/v2\/comments?post=2484"}],"version-history":[{"count":3,"href":"https:\/\/webs.uab.cat\/molbiomed\/en\/wp-json\/wp\/v2\/posts\/2484\/revisions"}],"predecessor-version":[{"id":2487,"href":"https:\/\/webs.uab.cat\/molbiomed\/en\/wp-json\/wp\/v2\/posts\/2484\/revisions\/2487"}],"wp:attachment":[{"href":"https:\/\/webs.uab.cat\/molbiomed\/en\/wp-json\/wp\/v2\/media?parent=2484"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/webs.uab.cat\/molbiomed\/en\/wp-json\/wp\/v2\/categories?post=2484"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/webs.uab.cat\/molbiomed\/en\/wp-json\/wp\/v2\/tags?post=2484"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}