Fast prediction of deleterious angiogenin mutations causing amyotrophic lateral sclerosis. Issue 12 (9th May 2013)

• Record Type: Journal Article
• Authors: Padhi, Aditya K.; Vasaikar, Suhas V.; Jayaram, Bhyravabhotla; Gomes, James
• Is Part Of: FEBS letters. Volume 587:Issue 12(2013)
• Page Start: 1762
• Page End: 1766
• Publication Date: 2013-05-09
• Subjects: Angiogenin -- Amyotrophic lateral sclerosis -- Single nucleotide polymorphism -- Molecular dynamics -- Deleterious mutation; Biochemistry -- Periodicals; Biophysics -- Periodicals; Molecular biology -- Periodicals; Biochimie -- Périodiques; Biochemistry; Biophysics; Molecular biology; Periodicals; 572.05
• DOI: 10.1016/j.febslet.2013.04.022
• Languages: English
• ISSNs: 0014-5793

Abstract

Abstract : Certain single nucleotide polymorphisms causing missense mutations in angiogenin result in its loss‐of‐function and onset of amyotrophic lateral sclerosis (ALS). Although several such associations are reported across diverse ethnic groups, no method is available for predicting if a new mutation is deleterious. We present here a fast molecular dynamics based method for determining the mechanisms of functional loss caused by mutations, and attributes to ascertain whether a mutation causes ALS. Abstract : Functional loss mechanisms of angiogenin mutants causing ALS are poorly understood. Conformational switching of His114 causes loss of ribonucleolytic activity. Local folding of 31 RRR 33 residues results in loss of nuclear translocation activity. Hydrogen bond interactions correlate with loss of ribonucleolytic activity. Deleterious angiogenin mutations causing ALS can be predicted quickly.