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Targeted genomic studies are required to understand complex polygenic disorders such as Diabetes. In this context our approach was to detect the polymorphism in ATP-sensitive potassium (KATP) channel protein subunit Kir6.2. Blood samples of normal and type2 diabetic patients in and around the Chittoor district were obtained. Amplification of Kir6.2 gene was done by custom designed primers from genomic DNA of normal and type2 diabetic patients and amplification products were sent for sequencing. Three mutations i.e., R177G, C344R, V138L corresponding to the region of Kir6.2 has been identified in comparative analysis. The crystal structure of Kir6.2 protein model is not available so far in any database and hence we modeled the structure using Modeller software tool and validated the stereo chemical quality of modeled structure by using PROCHECK and ProsaWeb model. Mutated conformations were generated after the introduction of the R177G, C344R and V138L mutations and subsequent energy minimization and molecular dynamics were done. RMSDs were observed to be 5.406 Å, 5.123 Å and 5.449 Å for R177G, V138L and C344R mutated structures respectively and these conformational and RMSD variations were observed to affect the functionality of the K ATP sensitive channels there by leads to increased glucose levels.
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Author(s): Chakravarthi VP Kumar YN Mahamanjunath K Rukmini A Bhavani D Kiran JAP Chiranjeevi T Ismail M Prasad JD Bhaskar M
KCNJ11, mutations, variants, K ATP sensitive channels