Homology modelling and in silico substrate-binding analysis of a Rhizobium sp. RC1 haloalkanoic acid permease

摘要

ABSTRACT Rhizobium sp. RC1 grows on haloalkanoic acid (haloacid) pollutants and expresses a haloacid permease (DehrP), which mediates the uptake of haloacids into the cells. For the first time, we report the homology model and docking analysis of DehrP and propose its putative binding residues. Ligand structures were retrieved from the ChemSpider database. The three-dimensional (3D) structure of DehrP was modelled based on the structure of Staphylococcus epidermidis glucose:H + symporter (GlcPse) by Phyre 2 , refined by 3D refine and evaluated by ProSA z -score, ERRAT and RAMPAGE. The 3D structure of the DehrP protein has 12 transmembrane helices. The overall quality factor of the model is ?￠????91%, with 93.6% of the residues in the favoured region and the z -score (?￠????2.86) falls within the range (?￠???¤10) for a good model. Subsequent docking of monobromoacetate, monochloroacetate, dibromoacetate, dichloroacetate, trichloroacetate and 2,2-dichloropropionate ligands via AutoDock Vina1.1.2 showed that residues Gln 133 , Asp 36 and Arg 130 are the putative H + -binding site, while the probable haloacid interacting residues are Glu 33 , Trp 34 , Phe 37 , Phe 38 , Gln 165 and Glu 370 . The DehrP-haloacid complexes exhibited binding affinities between ?￠????2.9 and ?￠????4.0????kcal/mol. Both the putative H + and haloacid-binding sites of DehrP possibly aided in co-transportation of substrates H + and haloacids into the bacterial cells through the alternating access mechanism, which occurs by formation of halogen bonds and van der Waals interactions with the substrates. Hence, site-directed mutagenesis on the DehrP binding residues could improve the haloacid-binding affinity for efficient haloacid degradation.