Molecular modelling and Function Prediction of hABH7, human homologue of _E. coli_ ALKB7

Human homologues of ALKB protein have shown the prime role in DNA damaging drugs, used for cancer therapy. Little is known about structure and function of hABH7, one of the members of this superfamily. Therefore, in the present study we intend to predict its structure and function using various bioinformatics tools. Modeling was done with modeller 9v7 to predict the 3D structure of the hABH7 protein. The tertiary structure model of hABH7, ALKBH7.B99990002.pdb was predicted and evaluated. Validation results showed 97.8% residues in favored and additional allowed regions of Ramachandran plots. Ligand binding residues prediction showed four ligand clusters, having 25 ligands in cluster 1. Importantly, presence of a Phe120-Gly121-Gly122 conserved pattern in the functional domain was detected. In the predicted structural model of hABH7, amino acid residues, Arginine at 57, 58, 59 and 60 along with tyrosine at 61 were predicted in RNA binding sites of the model. The predicted and validated model of human homologue hABH7 resulting from this study may unveil the mechanism of DNA damage repair in humans and accelerate the research on designing appropriate inhibitors aiding in chemotherapy and cancer related diseases

Structure and function prediction of human homologue hABH5 of _E. coli_ ALKB5 using in silico approach

Newly discovered human homologues of ALKB protein have shown the activity of DNA damaging drugs, used for cancer therapy. Little is known about the structure and function of hABH5, one of the members of this superfamily. Therefore, in the present study we intend to predict its structure and function using various bioinformatics tools. Modeling was done with modeler 9v7 to predict the 3D structure of the hABH5 protein. 3-D model of hABH5, ALKBH5.B99990005.pdb was predicted and evaluated. Validation results showed 96.8% residues in favor and an additional allowed region of the Ramachandran plot. Ligand binding residues prediction showed four ligand clusters, having 25 ligands in cluster 1. Importantly, conserved pattern of Pro158-X-Asp160-Xn-His266 in the functional domain was detected. DNA and RNA binding sites were also predicted in the model. The predicted and validated model of human homologue hABH5 resulting from this study may unveil the mechanism of DNA damage repair in humans and accelerate research on designing appropriate inhibitors, aiding in chemotherapy and cancer related diseases

Pathogenic Huntingtin Repeat Expansions in Patients with Frontotemporal Dementia and Amyotrophic Lateral Sclerosis.

We examined the role of repeat expansions in the pathogenesis of frontotemporal dementia (FTD) and amyotrophic lateral sclerosis (ALS) by analyzing whole-genome sequence data from 2,442 FTD/ALS patients, 2,599 Lewy body dementia (LBD) patients, and 3,158 neurologically healthy subjects. Pathogenic expansions (range, 40-64 CAG repeats) in the huntingtin (HTT) gene were found in three (0.12%) patients diagnosed with pure FTD/ALS syndromes but were not present in the LBD or healthy cohorts. We replicated our findings in an independent collection of 3,674 FTD/ALS patients. Postmortem evaluations of two patients revealed the classical TDP-43 pathology of FTD/ALS, as well as huntingtin-positive, ubiquitin-positive aggregates in the frontal cortex. The neostriatal atrophy that pathologically defines Huntington's disease was absent in both cases. Our findings reveal an etiological relationship between HTT repeat expansions and FTD/ALS syndromes and indicate that genetic screening of FTD/ALS patients for HTT repeat expansions should be considered