Ighmbp2 mutations and disease pathology: Defining differences that differentiate SMARD1 and CMT2S.

Mutations in the Immunoglobulin mu DNA binding protein 2 (IGHMBP2) gene result in two distinct diseases, SMA with Respiratory Distress Type I (SMARD1) and Charcot Marie Tooth Type 2S (CMT2S). To understand the phenotypic and molecular differences between SMARD1 and CMT2S, and the role of IGHMBP2 in disease development, we generated mouse models based on six IGHMBP2 patient mutations. Previously, we reported the development and characterization of Ighmbp2 mice and in this manuscript, we examine two mutations: D565N (D564N in mice) and H924Y (H922Y in mice) in the Ighmbp2 and Ighmbp2 contexts.

Applications of Surface Plasmon Resonance (SPR) to the Study of Diverse Protein-Ligand Interactions.

Functional characterization of enzymes/proteins requires determination of the binding affinity of small molecules or other biomolecules with the target proteins. Several available techniques, such as proteomics and drug discovery strategies, require a precise and high-throughput assay for rapid and reliable screening of potential candidates for further testing. Surface plasmon resonance (SPR), a well-established label-free technique, directly measures biomolecular affinities.

Inhibitors against DNA Polymerase I Family of Enzymes: Novel Targets and Opportunities.

DNA polymerases replicate cellular genomes and/or participate in the maintenance of genome integrity. DNA polymerases sharing high sequence homology with DNA polymerase I (pol I) have been grouped in Family A. Pol I participates in Okazaki fragment maturation and in bacterial genome repair.

The contribution and therapeutic implications of IGHMBP2 mutations on IGHMBP2 biochemical activity and ABT1 association.

Mutations within immunoglobulin mu DNA binding protein (IGHMBP2), an RNA-DNA helicase, result in SMA with respiratory distress type I (SMARD1) and Charcot Marie Tooth type 2S (CMT2S). The underlying biochemical mechanism of IGHMBP2 is unknown as well as the functional significance of IGHMBP2 mutations in disease severity. Here we report the biochemical mechanisms of IGHMBP2 disease-causing mutations D565N and H924Y, and their potential impact on therapeutic strategies.