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

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 Phyre², 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 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.

KEYWORDS:

• Rhizobium sp. RC1
• haloacid permease
• binding analysis
• homology modelling
• docking simulation

Acknowledgments

M.A. Musa thanks the Nigerian Goverment for the Studenship award 2014/2015.

Disclosure statement

No potential conflict of interest was reported by the authors.

Additional information

Funding

This work was supported by the Research University Grant Scheme [grant numbers Q.J130000.2545.12H91 & Q.J130000.2526.13H09] from the Universiti Teknologi Malaysia. The funding body had no role in the design of the study and collection, analysis, and interpretation of data and in writing of the manuscript. M.A. Musa thanks the Kaduna State Government of Nigeria for Overseas Scholarship Scheme Award.