Proteinkovalenter

Proteinkovalenter is a term used to describe covalent linkages that join proteins or protein residues, creating stable, covalently bonded assemblies. The concept covers both cross-links within a single protein (intra-molecular) and between different proteins (inter-molecular), as well as covalent attachments of modifiers such as ubiquitin, SUMO, or NEDD8 to lysine or other residues. In this sense, proteinkovalenter emphasizes the covalent nature of these connections, in contrast to non-covalent interactions that often dominate protein complexes.

Common mechanisms included under proteinkovalenter are disulfide bonds between cysteine residues, which stabilize many secreted and extracellular proteins; transglutaminase-catalyzed cross-links that create isopeptide bonds between glutamine and lysine residues in structural proteins; and covalent attachments of ubiquitin or related modifiers that regulate protein stability, localization, and activity. Covalent adducts formed by small-molecule inhibitors or natural products that irreversibly modify enzyme active sites are also included, as they create a lasting link between the protein and the modifying entity.

Proteinkovalenter are studied with methods such as cross-linking mass spectrometry, high-resolution mass spectrometry, X-ray crystallography, and cryo-electron microscopy, often complemented by mutagenesis and biochemical assays. These covalent connections influence protein stability, signaling, and the assembly of macromolecular complexes. Abnormal patterns of covalent linkage can be involved in aging or disease processes, including altered tissue mechanics from collagen cross-linking and dysregulated proteostasis from ubiquitin-related pathways.

In research and pharmacology, proteinkovalenter also describe covalent drugs that form lasting bonds with targets, offering prolonged effects while raising considerations of selectivity and safety.