Structural Insight into Anaphase Promoting Complex 3 Structure and Docking with a Natural Inhibitory Compound

Adv Biomed Res. 2017 Mar 7:6:26. doi: 10.4103/2277-9175.201683. eCollection 2017.

Abstract

Background: Anaphase promoting complex (APC) is the biggest Cullin-RING E3 ligase and is very important in cell cycle control; many anti-cancer agents target this. APC controls the onset of chromosome separation and mitotic exit through securin and cyclin B degradation, respectively. Its APC3 subunit identifies the APC activators-Cdh1 and Cdc20.

Materials and methods: The structural model of the APC3 subunit of APC was developed by means of computational techniques; the binding of a natural inhibitory compound to APC3 was also investigated.

Results: It was found that APC3 structure consists of numerous helices organized in anti-parallel and the overall model is superhelical of tetratrico-peptide repeat (TPR) domains. Furthermore, binding pocket of the natural inhibitory compound as APC3 inhibitor was shown.

Conclusion: The findings are beneficial to understand the mechanism of the APC activation and design inhibitory compounds.

Keywords: Anaphase promoting complex; bioinformatics; tetratrico-peptide repeat domain.