Genomic Studies in a Large Cohort of Hearing Impaired Italian Patients Revealed Several New Alleles, a Rare Case of Uniparental Disomy (UPD) and the Importance to Search for Copy Number Variations.

Hereditary hearing loss (HHL) is a common disorder characterized by a huge genetic heterogeneity. The definition of a correct molecular diagnosis is essential for proper genetic counseling, recurrence risk estimation, and therapeutic options. From 20 to 40% of patients carry mutations in gene, thus, in more than half of cases it is necessary to look for causative variants in the other genes so far identified (~100).

A Strategy to Enhance Secretion of Extracellular Matrix Components by Stem Cells: Relevance to Tissue Engineering.

The ability of cells to secrete extracellular matrix proteins is an important property in the repair, replacement, and regeneration of living tissue. Cells that populate tissue-engineered constructs need to be able to emulate these functions. The motifs, KTTKS or palmitoyl-KTTKS (peptide amphiphile), have been shown to stimulate production of collagen and fibronectin in differentiated cells.

Impact of disease-causing mutations on inter-domain interactions in cMyBP-C: a steered molecular dynamics study.

The molecular interactions of the sarcomeric proteins are essential in the regulation of various cardiac functions. Mutations in the gene MYBPC3 coding for cardiac myosin-binding protein-C (cMyBP-C), a multi-domain protein, are the most common cause of hypertrophic cardiomyopathy (HCM). The N-terminal complex, C1-motif-C2 is a central region in cMyBP-C for the regulation of cardiac muscle contraction.

An Investigation of the Molecular Mechanism of Double cMyBP-C Mutation in a Patient with End-Stage Hypertrophic Cardiomyopathy.

Mutations in the gene coding for cardiac myosin binding protein-C (cMyBP-C), a multi-domain (C0-C10) protein, are a major causative factor for inherited hypertrophic cardiomyopathy. Patients carrying mutations in this gene have an extremely heterogeneous clinical course, with some progressing to end-stage heart failure. The cause of this variability is unknown.

Molecular modeling of disease causing mutations in domain C1 of cMyBP-C.

Cardiac myosin binding protein-C (cMyBP-C) is a multi-domain (C0-C10) protein that regulates heart muscle contraction through interaction with myosin, actin and other sarcomeric proteins. Several mutations of this protein cause familial hypertrophic cardiomyopathy (HCM). Domain C1 of cMyBP-C plays a central role in protein interactions with actin and myosin.

Molecular modeling study on orphan human protein CYP4A22 for identification of potential ligand binding site.

A molecular structure is an essential source to identify ligand binding sites in orphan human cytochrome P450 4A22 (CYP4A22) that belongs to family 4, which is known to be involved in the regulation of blood pressure. Thus, a homology model has been constructed for CYP4A22 and refined by molecular dynamics simulation (MDS). Subsequently, molecular docking was performed with possible substrates, arachidonic acid (essential fatty acid, AA) and erythromycin (therapeutic drug, ERY).

Probing possible egress channels for multiple ligands in human CYP3A4: a molecular modeling study.

Human cytochrome P450 (CYP) 3A4 extensively contributes to metabolize 50% of the marketed drugs. Recently, a CYP3A4 structure with two molecules of ketoconazole (2KT) was identified. However, channels for egresses of these inhibitors are unexplored.

Molecular modeling study of CodX reveals importance of N-terminal and C-terminal domain in the CodWX complex structure of Bacillus subtilis.

In Bacillus subtilis, CodW peptidase and CodX ATPase function together as a distinctive ATP-dependent protease called CodWX, which participates in protein degradation and regulates cell division. The molecular structure of CodX and the assembly structure of CodW-CodX have not yet been resolved. Here we present the first three-dimensional structure of CodX N-terminal (N) and C-terminal (C) domain including possible structure of intermediate (I) domain based on the crystal structure of homologous Escherichia coli HslU ATPase.