A Novel Methodology for Structural, Functional and Toxicological Analysis of Mutant Angiogenin Protein in Human

Abstract

Introduction: Angiogenin is a protein of 14.1 kDa encoded by ANG gene and belongs to a superfamily of pancreatic ribonuclease A. Angiogenin is an effective stimulator of new blood vessels formation. It plays a vital role in the pathological as well as physiological mechanisms by regulating cell proliferation, differentiation and invasion. Mutation in ANG leads to a disease called amyotrophic lateral sclerosis 9. Amyotrophic lateral sclerosis 9 is a motor neuron disease that causes the decease of neurons, which controls the voluntary muscles of body. Material and Methods: The mutations F12S, P20S, Q36L, Y38H, K41E, D46G, S52N, R55K, C63W, K64I, I70V, K84E, P136L, V137I and H138R were selected for this study to investigate the single amino acid substitution effects on structure, function, stability and pathological impression on the protein. Results: The study revealed that the mutations Q36L, C63W, K64I, P136L, V137R and H138R have strong functional, structural and conformational effects compared to F12S, P20S, Y38H, K41E, S52N, R55K and K84E suggesting a high rate of disorder tendency. Conclusion: The in silico analysis of angiogenin identified several point mutations which may cause ALS9. The results of this study may be useful in planning and conducting clinical work on the ANG gene to find out, which mutation is responsible for the major cause of amyotrophic lateral sclerosis 9.