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

Abstract

<p><i>Rhizobium</i> 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 <i>Staphylococcus epidermidis</i> glucose:H⁺ symporter (GlcPse) by Phyre², refined by 3D^refine and evaluated by ProSA <i>z</i>-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 <i>z</i>-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 <i>via</i> AutoDock Vina1.1.2 showed that residues Gln¹³³, Asp³⁶ and Arg¹³⁰ are the putative H⁺-binding site, while the probable haloacid interacting residues are Glu³³, Trp³⁴, Phe³⁷, Phe³⁸, Gln¹⁶⁵ and Glu³⁷⁰. 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.</p