Molecular Modelling Studies on the Binding of Phenylurea Inhibitors to the D 1 Protein of Photosystem II

Abstract

A hypothetical molecular model of part of the D 1 protein of photosystem II, based on the analogous portion of the L subunit of the Rhodopseudomonas viridis reaction centre, has been used to study the binding of an extended hydrophobic phenylurea inhibitor (N,N-dimethyl-carbamoyl)4 -amino-4 ′-chloro-trans-stilbene) (I) to the QB site. The inhibitor was fitted by eye into a cleft in the site, and a limited part of the inhibitor/D 1 complex was energy minimized. The gross orientation of the inhibitor placed the dimethylurea moiety towards the predicted binding domain of the plastoquinone head group, and the stilbene moiety directed along the quinone isoprenoid side chain binding domain, suggesting a similar pathway of approach of the two molecules from the membrane into the binding site. Binding interactions of the inhibitor included hydrogen bonds to the side chain hydroxyl of ser 264 and the peptide carbonyl group of ala 251, with the side chain hydroxyl of ser 268 as an alternative ligand. Numerous hydrophobic contacts were also possible. Although phenylureas do not bind to reaction centres of Rp. viridis, many of the binding interactions to D1 could also be detected in Rp. viridis. However, the β-CH2 and δ-CO2-groups of glu 212 in Rp. viridis are located in the corresponding region of D1 occupied by the dimethylurea moiety of the inhibitor in our model of its binding to D 1. This may explain why diuron (DCMU) does not bind to Rp. viridis reaction centres.

Modeling of the D1/D2 proteins and cofactors of the photosystem II reaction center: Implications for herbicide and bicarbonate binding

“…Based on the model, he also proposed important residues involved in Q B and the non-heme iron binding. Bowyer et al (1990) constructed a model (using the sequence from Synechococcus 7942) for the QB and herbicide-binding niche in the Dl protein, by digitizing the stereoimage of part of the Rps. viridis structure.…”

Sequence analysis of photoaffinity‐labelled peptides derived by proteolysis of photosystem‐2 reaction centres from thylakoid membranes treated with [14C]azidoatrazine

“…The QB site of D1 has been modelled [26,271 and the interaction of phenylurea herbicides at their binding site studied [28]. The herbicide-binding site is surrounded by three regions of a-helix, the D (residues 196-222), DE (residues 249-259) and E (residues 268-293) helices, as well as the segment connecting the DE and E helices and possibly the loop connecting the D and DE helices.…”

“…The QB site of the bacterial reaction centre is located on the L subunit and the availability of the crystal structures of bacterial reaction centres from Rhodopseudomonas viridis [22, 231 and Rhodobacter sphaeroides [24,25] has enabled construction of a model of the QB site on the D1 polypeptide of PS2 [26] (see also [27]). This model has been used to examine phenylurea binding to PS2 and the failure of phenylurea herbicides to bind effectively to bacterial reaction centres [28].…”

A tribute to Achim Trebst, a friend

“…This gave impetus to several laboratories, including that of Tony Crofts and my own, for the homology modeling of Photosystem II (Crofts et al 1987;Bowyer et al 1990;Xiong et al 1996Xiong et al , 1998, using results from the exciting data of the Nobel laureates Hartmut Michel, Johann Deisenhofer, Robert Huber and their coworkers on the reaction center of the purple bacteria (see e.g., Deisenhofer et al 1984Deisenhofer et al , 1985.…”