Staphylococcus aureus is a particularly virulent microorganism; the main impact is due to methicillin resistant strains of S. aureus (MRSA), commonly found in hospitals and community, creating an increased necessity to develop a new antibacterial therapy. In this context, shikimate kinase (SK) is an essential enzyme in the shikimic acid pathway, which is an essential route involved in the biosynthesis of aromatic compounds in this bacterium. Here an in silico approach was used to characterizes the S. aureus SK (SaSK) and find potential inhibitors. A 3D model of SaSK was constructed through homology modeling. Structural characterization was made using different programs such as Protparam, NPS Server, CYS_REC, and CASTp. A virtual screening protocol, into the active site of the enzyme, was applied to identify new potential inhibitors using Glide software. The “Drug like” subset of the ZINC small molecules database was used to this end, some physicochemical and drug likeness parameters were determined for these compounds. According to the structural analyses, alpha helices were the most predominant followed by random coils, extended strand and beta turns and potential disulfide bridges were no detected. Furthermore, a predicted isoelectric point of 5.09 were obtained. Virtual screening results showed that the three compounds with the highest binding energy were ZINC34616948 which made hydrogen bonds with Asp117, Glu57, Arg138 and Arg61; ZINC03162994 that formed hydrogen bonds with Asp37 and Asp117, a salt bridge with Asp37 and a π-π stacking with Phe60; and ZINC70632388 which made hydrogen bonds with Arg61 and Arg138, a salt bridge with Glu57, Arg61 and Arg138. The structural data as well as the potential inhibitors reported for SaSK will serve as a starting point to obtain a new drug against MRSA.

Structural characterization, homology modelling and virtual screening studies in shikimate kinase from methicillin resistant Staphylococcus aureus

253rd National Meeting (2017)

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