title: Specific triazine resistance in bacterial reaction centers induced by a single mutation in the QA protein pocket.
abstract: We report here the first example of a reaction center mutant from Rhodobacter sphaeroides, where a single mutation (M266His --> Leu) taking place in the primary quinone protein pocket confers selective resistance to triazine-type inhibitors (terbutryn, ametryn, and atrazine), which bind in the secondary quinone protein pocket, at about 13 A from the mutation site. The M266His --> Leu mutation involves one of the iron atom ligands. Interestingly, neither the secondary quinone nor the highly specific inhibitor stigmatellin binding affinities are affected by the mutation. It is noticeable that in the M266His --> Ala mutant a nativelike behavior in observed. We suggest that the long side chain of Leu in position M266 may lack space to accommodate in the Q(A) pocket therefore transferring its hindrance to the Q(B) pocket. This may occur via the structural feature formed by the Q(A)-M219His-Fe-L190His-inhibitor (or Q(B)) connection, pushing L189Leu and/or L229Ile in closer contact to the triazine molecules, therefore decreasing their bindings. This opens the possibility to finely tune, in reaction center proteins, the affinity for herbicides by designing mutations distant from their binding sites.
authors.affiliation: Laboratoire de Chimie-Physique, UMR 8000, Bât. 350, Faculté d'Orsay, 91405 Orsay Cedex, France.
authors.forename: Jean-Alexis
authors.initials: JA
authors.lastname: Spitz
authors.forename: Valérie
authors.initials: V
authors.lastname: Derrien
authors.forename: Laura
authors.initials: L
authors.lastname: Baciou
authors.forename: Pierre
authors.initials: P
authors.lastname: Sebban
mesh_terms: D001280:Atrazine / Q000037:antagonists & inhibitors / Q000737:chemistry; D016227:Benzoquinones / Q000737:chemistry; D001667:Binding, Competitive / Q000235:genetics; D024881:Drug Resistance, Bacterial / Q000235:genetics*; D006639:Histidine / Q000235:genetics; D007930:Leucine / Q000235:genetics; D008715:Methionine / Q000235:genetics; D008956:Models, Chemical; D016297:Mutagenesis, Site-Directed; D045332:Photosystem II Protein Complex / Q000737:chemistry* / Q000235:genetics* / Q000378:metabolism; D011090:Polyenes / Q000037:antagonists & inhibitors / Q000737:chemistry; D011485:Protein Binding / Q000235:genetics; D012242:Rhodobacter sphaeroides / Q000737:chemistry* / Q000235:genetics* / Q000254:growth & development; D014227:Triazines / Q000037:antagonists & inhibitors / Q000737:chemistry*
chemical_list: D016227:Benzoquinones; D045332:Photosystem II Protein Complex; D011090:Polyenes; D014227:Triazines; C100057:ametryne; C004532:quinone; D006639:Histidine; C041573:stigmatellin; D008715:Methionine; D007930:Leucine; D001280:Atrazine; C010347:terbutryne