In silico study of IMPDH۲ interactions with proteins involved inWnt/ -catenin pathway

The Wnt/ -catenin pathway is a well-known signaling pathway that is involved with many physiological and developmental processes. The aberrant functions of this pathway have been reported in many cancers. -catenin, the prominent mediator of this pathway is regulated by a destruction complex. IMPDH۲ which is the rate-limiting enzyme in guanine nucleotides synthesis and the dominant isozyme in cancer, is related to the Wnt/ -catenin pathway, reciprocally. In this study, we sought to elucidate the interactions of IMPDH۲ with different proteins of the Wnt/ -catenin pathway at the molecular level. Hence, after retrieving and preparing the proteins structures from PDB database, the protein-protein docking was conducted using HDOCK server. Thereafter, the attained docking models were visualized and analyzed by PyMOL software. The results show that IMPDH۲ interacts with -catenin with a docking score of -۲۶۶.۶۲. The docking scores for IMPDH۲ interactions with the proteins of destruction complex such as APC, AXIN, CK۱↵, and GSK۳ were -۲۳۵.۰۲, -۲۳۰.۴۱, -۲۸۲.۴۰, and -۲۷۲.۸۲, respectively. Next, we found that the interface of IMPDH۲- -catenin complex is composed mainly of hydrophobic R-chain residues (۳۸.۳%). However, in the case of CK۱↵ as the most likely protein of destruction complex which interacts with IMPDH۲, the uncharged polar R-chain residues are remarkable (۴۴.۶%). These results show that IMPDH۲ could directly interact with catenin and also may affect this protein through interaction with proteins of destruction complex such as CK۱↵. So, our findings support previous reports on the correlation of IMPDH۲ with the Wnt/ -catenin pathway and provide a better understanding of these interactions at the protein-protein level. Considering the residues involved in each interaction could be useful in future research on drug design for targeting the Wnt/ -catenin pathway in cancer

کلیدواژه ها:

IMPDH۲ ، Wnt/ -catenin pathway ، CK۱↵ ، Protein-Protein Interaction