Molecular Impairment Mechanisms of Novel OPA1 Mutations Predicted by Molecular Modeling in Patients With Autosomal Dominant Optic Atrophy and Auditory Neuropathy Spectrum Disorder.

Hypothesis: Different missense mutations of the optic atrophy 1 gene (OPA1) identified in optic atrophy patients with auditory neuropathy spectrum disorder (ANSD) induce functional impairment through different molecular mechanisms.

Background: OPA1 is the gene responsible for autosomal dominant optic atrophy (ADOA), but some of its mutations are also associated with ANSD. OPA1 is a member of the GTPase family of proteins and plays a key role in the maintenance of mitochondrial activities that are dependent on dimer formation of the protein.

Folding pathways of human telomeric type-1 and type-2 G-quadruplex structures.

We have investigated new folding pathways of human telomeric type-1 and type-2 G-quadruplex conformations via intermediate hairpin and triplex structures. The stabilization energies calculated by ab initio methods evidenced the formation of a hairpin structure with Hoogsteen GG base pairs. Further calculations revealed that the G-triplet is more stable than the hairpin conformation and equally stable when compared to the G-tetrad.

Vestibular dysfunction in a Japanese patient with a mutation in the gene OPA1.

OPA1 mutations are known to cause autosomal dominant optic atrophy (ADOA), and some types of OPA1 mutations also cause auditory neuropathy. In the present study, we evaluated the vestibular dysfunction that accompanied auditory neuropathy in a patient with an OPA1 mutation. A caloric test failed to elicit nystagmus or dizziness in either ear.

RNA aptamers specifically interact with the Fc region of mouse immunoglobulin G.

We have designed the in vitro selection method to obtain some aptamers such as a general antibody-probing agent, which might bind to the constant regions of mouse immunoglobulin G (IgG) subclasses. As a consequence, one of the selected aptamers found to recognize mouse IgG1, 2a, and 3 subclasses. According to the binding assay, it is suggested that this aptamer recognizes the constant regions of mouse IgG subclass.

Folding pathways of hybrid-1 and hybrid-2 G-quadruplex structures.

The G-rich sequence in the human telomeric DNA can form the G-quadruplex structure. The G-quadruplex structure has become an attractive target for the anticancer drugs, because it effectively inhibits telomerase activity. Recently, the human telomere G-quadruplex in K(+) solution has been determined as a hybrid structure.

Structural stability analysis of the intermediates in the folding pathway of human telomeric hybrid-1 G-quadruplex based on fragment molecular orbital method.

The human telomeric DNA sequence d[AGGG(TTAGGG)(3)] has been found to form different type of G-quadruplex structure based on NMR(1), X-ray crystallography(2) and circular dichroism (CD). Recently human telomeric hybrid-1 G-quadruplex structure in K(+) solution has been revealed by CD and NMR(3,4,5). However, folding pathway of G-quadruplex structures is not clear to date.

X-ray structures of Aerococcus viridans lactate oxidase and its complex with D-lactate at pH 4.5 show an alpha-hydroxyacid oxidation mechanism.

L-Lactate oxidase (LOX) belongs to a family of flavin mononucleotide (FMN)-dependent alpha-hydroxy acid-oxidizing enzymes. Previously, the crystal structure of LOX (pH 8.0) from Aerococcus viridans was solved, revealing that the active site residues are located around the FMN.