title: Dynamics of different arachidonic acid orientations bound to prostaglandin endoperoxide synthases.
abstract: Prostaglandin endoperoxide synthases (PGHSs) catalyze the conversion of arachidonic acid (AA) into prostaglandin endoperoxide H(2). This reaction requires a specific orientation of AA within the active site, but an alternative crystallographic binding orientation for AA also exists. Since the origin of this alternative complex, and its potential relevance, have been neglected so far, we have characterized the dynamics of both orientations of AA, bound to PGHS-1 and -2, in order to obtain new insights for designing PGHSs inhibitors. Our results indicate that AA in the alternative orientation seems to be less stable, moving toward Arg120. Such potentially minor orientation of AA can be related to crystallographic complexes of anti-inflammatory agents, pointing to an alternate SAR on PGHSs inhibitors.
authors.affiliation: Centro de Biotecnologia, Universidade Federal do Rio Grande do Sul, Av. Bento Gonçalves 9500, CP 15005, Porto Alegre 91500-970, RS, Brazil.
authors.forename: Liana Guimarães
authors.initials: LG
authors.lastname: Sachett
authors.forename: Hugo
authors.initials: H
authors.lastname: Verli
mesh_terms: D000818:Animals; D016718:Arachidonic Acid / Q000737:chemistry / Q000378:metabolism*; D020134:Catalytic Domain; D016861:Cyclooxygenase Inhibitors / Q000737:chemistry* / Q000494:pharmacology; D015195:Drug Design; D051379:Mice; D056004:Molecular Dynamics Simulation; D011451:Prostaglandin-Endoperoxide Synthases / Q000737:chemistry* / Q000378:metabolism*; D011485:Protein Binding; D034561:Sheep, Domestic; D013379:Substrate Specificity
chemical_list: D016861:Cyclooxygenase Inhibitors; D016718:Arachidonic Acid; D011451:Prostaglandin-Endoperoxide Synthases