Mulyani R, Destiarani W, Rahmawati UM, Yusuf M, Subroto T, Iman P. Maksum*
Diabetic mellitus and cataracts are common mitochondrial diseases in Indonesia, occurring as a result of a lack of ATP, which is produced in mitochondria via oxidative phosphorylation (OXPHOS). The OXPHOS chain is composed of five complex proteins encoded by genes from nuclear DNA and mitochondrial DNA. One such gene is the CYB gene, with its locus in mitochondrial DNA. The CYB gene encodes part of the complex III subunit, cytochrome b, an electron transfer agent. A novel mutation has been identified at T15458C in type 2 diabetes mellitus patients and T15663C in cataract patients, both of which are in the CYB gene, leading to amino acid alterations S238P and I306T. This study investigated the relationship between T15458C and T15663C mutations in the CYB gene of mitochondrial DNA to the OXPHOS process via an in silico method. Wild type and mutant CYB were modelled via homology modelling using Modeller 9.19 with a 5XTE template, then evaluated using the Ramachandran plot, packaging quality score, and the DOPE profile. The results of the S238P mutant structure analysis showed that proline acts as a helix-breaker due to the loss of a hydrogen bond, while I306T causes a hydrophobic interaction as the helix stabiliser is lost in the mutant. It is assumed the threonine was phosphorylation mutations also destabilises the complex, as proven by the ΔΔG < 0. In conclusion, S238P and I306T mutations affect the function of complex III as an electron transfer agent in the respiratory process.
Published Date: 2021-01-15;