Homology Modelling and in Silico Substrate Binding Analysis of a Rhizobium sp. RC1 Haloalkanoic Acid Permease
DOI:
https://doi.org/10.18034/mjmbr.v7i1.485Keywords:
Docking, Haloacids, Homology modelling, Permease, Rhizobium sp. RC1Abstract
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 proposed its putative binding residues. The Protein Data Bank for protein of similar sequence. Ligand structures were retrieved from the ChemSpider database. The 3-dimensional (3-D) structure of DehrP was modelled based on the structure of Staphylococcus epidermidis glucose: H+ symporter (GlcPse) by Phyre2, refined by 3Drefine and evaluated by ProSA z-score, ERRAT and RAMPAGE. Docking of monobromoacetate, monochloroacetate, dibromoacetate, dichloroacetate, trichloroacetate, and 2,2-dichloropropionate ligands was done with AutoDock vina1.1.2. The 3-D structure of DehrP protein has twelve transmembrane helices. The overall quality factor of the model is ∼91%, with 93.6% of the residues in the favored region and the z-score is within the ≤ 10 limit. The putative H+ binding site residues are Gln133, Asp36, and Arg130. Docking analysis showed that Glu33, Trp34, Phe37, Phe38, Gln165, and Glu370 are potential haloacid interacting residues. DehrP-haloacid complexes had a binding affinity between -2.9 to -4.0 kcal/mol. DehrP has both putative H+ and haloacid binding sites that are most likely involved in the co-transport of H+ and haloacids. DehrP interacts with haloacids majorly through van der Waals and halogen bond interactions and has greater affinity for 2,2-dichloropropionate and could be a specialized chloropropionate uptake system. Site-directed mutagenasis of DehrP binding residues could improve its haloacid binding affinity.
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