Microsecond simulation analysis of carbonic anhydrase – II in complex with (+)-cathechin revealed molecular interactions responsible for its amelioration effect on fluoride toxicity

Abstract

Fluorosis is a chronic condition caused by overexposure to fluoride, marked by impaired dental, skeletal, and non-skeletal health. In presence of excess fluoride ions, in severe cases calcification of the ligaments observed. Earlier studies have suggested that the disruption of carbonic anhydrase activity via ionic homeostasis change was associated with F toxicity. In a recent study, it was demonstrated that Tamarind fruit extract was effective in increasing the urinary F excretion in male Wistar rats via studying the mRNA expression of carbonic anhydrase II (CA II) in kidney homogenates using western blotting, immunohistochemistry and quantitative Realtime PCR based studies. We have carried out this study to understand the detailed molecular level interactions responsible for this tamarind extract based (+)-cathechin compound towards lowering the F toxicity via targeting CA-II. From our study, it was revealed that due to the ability of (+)-cathechin compound to bind tightly filling complete available space at the catalytically important site forming metal coordinated ionic bonds with His94, His96 and His119 residues helps in restricting F ions to interact with Zn ion located at the core of catalytic site responsible for its functionality. On the other hand, interaction of (+)-cathechin compound with Gln92 was observed to be critically important towards inducing conformational changes in CA-II, thus allowing (+)-cathechin compound to burry even deeply inside the catalytic site.

Communicated by Ramaswamy H. Sarma

Keywords:

• Fluorosis
• carbonic anhydrase II
• (+)-cathechin
• tamarind fruit extract
• molecular modeling
• docking
• MD simulations

Disclosure statement

The authors declare that they have no conflict of interests.

Authors’ contribution

Pulala Raghuveer Yadav designed the study. Syed Hussain Basha and Pulala Raghuveer Yadav executed the work and generated the data. Pulala Raghuveer Yadav, Syed Hussain Basha, Sadam DV Satyanarayana and Pavan Kumar Pindi analyzed the data and wrote the manuscript. All authors have read and approved the final manuscript.