Keratin 28 Inhibitors

Chemical inhibitors of Keratin 28 can disrupt its structure and function through various mechanisms. Dithiothreitol (DTT) targets the disulfide bonds which are pivotal for the three-dimensional integrity of Keratin 28. By reducing these bonds, DTT can cause the protein's structure to unfold, thereby inhibiting its function. Urea, in high concentrations, can lead to the denaturation of Keratin 28 by disrupting non-covalent interactions, such as hydrogen bonds, which help maintain the protein's secondary and tertiary structure. The denaturing effect of urea is compounded when used in combination with reducing agents like DTT, enhancing the disruption of Keratin 28's structure. On the other hand, sodium dodecyl sulfate (SDS) is an anionic detergent that can solubilize and unfold Keratin 28 by disrupting hydrophobic interactions within the protein, leading to a loss of functional conformation. Iodoacetamide acts by alkylating the cysteine residues of Keratin 28, preventing the formation of disulfide bridges that stabilize the protein's structure. This alkylation results in a functional inhibition due to the lack of proper folding. N-Ethylmaleimide (NEM) also targets sulfhydryl groups on cysteine residues, similarly blocking the formation of disulfide bonds that are essential for the correct assembly and stability of Keratin 28 filaments. Phenylmethylsulfonyl fluoride (PMSF) preserves Keratin 28's structure by inhibiting serine proteases that could otherwise cleave and degrade the protein, thus preventing its functional decline. Cadmium chloride can disrupt metal-dependent conformational stability in proteins, and since keratins such as Keratin 28 may rely on zinc or other metals for structural integrity, cadmium can replace these essential metals and lead to functional inhibition. Ethanol affects Keratin 28 by perturbing hydrophobic interactions, high concentrations can denature the protein, affecting its structural and functional integrity. Benzalkonium chloride, being a surfactant, can compromise Keratin 28's structure by denaturing the protein, while acetone, a solvent, can precipitate and denature Keratin 28, disrupting its structural framework. Lastly, formaldehyde is capable of crosslinking the amino groups of proteins, forming methylene bridges between the lysine residues of Keratin 28, which can significantly alter the protein's natural configuration and lead to inhibition of its function.