{"id":1097,"date":"2022-07-01T09:00:46","date_gmt":"2022-07-01T07:00:46","guid":{"rendered":"https:\/\/webs.uab.cat\/dmrqb\/2022\/07\/01\/8th-european-workshop-on-lipid-mediator\/"},"modified":"2023-09-07T17:51:00","modified_gmt":"2023-09-07T15:51:00","slug":"8th-european-workshop-on-lipid-mediator","status":"publish","type":"post","link":"https:\/\/webs.uab.cat\/molbiomed\/en\/2022\/07\/01\/8th-european-workshop-on-lipid-mediator\/","title":{"rendered":"8th European Workshop on Lipid Mediator"},"content":{"rendered":"\n
Study of the conversion of leukotriene A4 to leukotriene B4 driven by leukotriene A4 hydrolase<\/h5>\n\n

Miquel Canyelles Ni\u00f1o<\/em><\/strong><\/a><\/h4>\n\n
LTA4<\/sub>H is a bifunctional zinc metalloenzyme that converts leukotriene A4<\/sub> (LTA4<\/sub>) into leukotriene B4<\/sub> (LTB4<\/sub>), one of the most potent chemotactic agents involved in acute and chronic inflammatory diseases. In this reaction, LTA4<\/sub>H acts as an epoxide hydrolase with a unique and fascinating mechanism, which includes the stereoselective attachment of one water molecule to the carbon backbone of LTA4<\/sub> several methylene units away from the epoxide moiety. By combining Molecular Dynamics simulations and Quantum Mechanics\/Molecular Mechanics calculations, we obtained a very detailed molecular picture of the different consecutive steps of that mechanism. By means of a rather unusual 1,7-nucleophilic substitution through a clear SN<\/sub>1 mechanism, the epoxide opens and the triene moiety of the substrate twists in such a way that the bond C6<\/sub>-C7<\/sub> adopts its cis<\/em> (Z<\/em>) configuration, thus exposing the R<\/em> face of C12<\/sub> to the addition of a water molecule hydrogen-bonded to ASP375. Thus, the two stereochemical features that are required for the bioactivity of LTB4<\/sub> appear to be closely related. The noncovalent \u03c0-\u03c0 stacking interactions between the triene moiety and two tyrosines (TYR267 and, especially, TYR378) that wrap the triene system along the whole reaction explain the preference for the cis<\/em> configuration inside LTA4<\/sub>H.<\/h5>\n\n
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Optimized structure of the zinc environment. Extracted figure Int. J. Mol. Sci.<\/em> 2022<\/strong>, 23<\/em>(6), 3140<\/figcaption><\/figure>\n<\/div>\n
Miquel Canyelles presented a poster entitled \u00abStudy of the conversion of leukotriene A4 to leukotriene B4 driven by leukotriene A4 hydrolase\u00bb which earned him the award as the best poster<\/em> of the congress.<\/strong><\/h5>\n
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Miquel Canyelles Ni\u00f1o and other winners \u2013 Karolinska Institutet<\/em>, Stockholm, Sweden<\/figcaption><\/figure>\n<\/div>","protected":false},"excerpt":{"rendered":"

Study of the conversion of leukotriene A4 to leukotriene B4 driven by leukotriene A4 hydrolase Miquel Canyelles Ni\u00f1o LTA4H is a bifunctional zinc metalloenzyme that converts leukotriene A4 (LTA4) into leukotriene B4 (LTB4), one of the most potent chemotactic agents involved in acute and chronic inflammatory diseases. In this reaction, LTA4H acts as an epoxide […]<\/p>\n","protected":false},"author":2580,"featured_media":0,"comment_status":"closed","ping_status":"closed","sticky":false,"template":"","format":"standard","meta":{"footnotes":""},"categories":[95,94,96],"tags":[99,98,97,101,102,100],"class_list":["post-1097","post","type-post","status-publish","format-standard","hentry","category-congresses","category-lipoxygenases","category-poster-en","tag-enzyme-catalysis","tag-leucotriene-a4-hidrolase","tag-leukotriene","tag-molecular-dynamics-simulations-en-2","tag-pro-inflammatory-lipidic-mediators","tag-qm-mm-calculations"],"_links":{"self":[{"href":"https:\/\/webs.uab.cat\/molbiomed\/en\/wp-json\/wp\/v2\/posts\/1097","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=1097"}],"version-history":[{"count":6,"href":"https:\/\/webs.uab.cat\/molbiomed\/en\/wp-json\/wp\/v2\/posts\/1097\/revisions"}],"predecessor-version":[{"id":2160,"href":"https:\/\/webs.uab.cat\/molbiomed\/en\/wp-json\/wp\/v2\/posts\/1097\/revisions\/2160"}],"wp:attachment":[{"href":"https:\/\/webs.uab.cat\/molbiomed\/en\/wp-json\/wp\/v2\/media?parent=1097"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/webs.uab.cat\/molbiomed\/en\/wp-json\/wp\/v2\/categories?post=1097"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/webs.uab.cat\/molbiomed\/en\/wp-json\/wp\/v2\/tags?post=1097"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}