Abstract
Covalent crosslinks within or between proteins play a key role in determining the structure and function of proteins. Some of these are formed intentionally by either enzymatic or molecular reactions and are critical to normal physiological function. Others are generated as a consequence of exposure to oxidants (radicals, excited states or two-electron species) and other endogenous or external stimuli, or as a result of the actions of a number of enzymes (e.g., oxidases and peroxidases). Increasing evidence indicates that the accumulation of unwanted crosslinks, as is seen in ageing and multiple pathologies, has adverse effects on biological function. In this article, we review the spectrum of crosslinks, both reducible and non-reducible, currently known to be formed on proteins; the mechanisms of their formation; and experimental approaches to the detection, identification and characterization of these species.
Highlights
Mechanisms of Formation, Detection, The formation of covalently linked peptides and proteins plays a key role in many biological processes, both physiologically and pathologically
In order to rationalize the resistance of GPx enzymes to deselenation, it has been proposed that internal selenenyl amide (Se–N) linkages with neighboring amides involving five- or eight-membered rings [122] are formed during the catalytic cycle [123]
Tyr–Trp crosslinks have been detected in peptides and isolated proteins exposed to multiple oxidants, including a cytochrome c peroxidase mutant exposed to a heme iron-peroxide reaction [81]; in glucose-6-phosphate dehydrogenase (G6PDH) exposed to ROO [53]; model peptides exposed to pulsed UV light [166]; in lysozyme treated with ROO and exposed to photooxidation reactions mediated by riboflavin and rose
Summary
Mechanisms of Formation, Detection, The formation of covalently linked peptides and proteins plays a key role in many biological processes, both physiologically and pathologically These can be formed intentionally, such as in the oxidative folding of nascent proteins within mammalian cells in the endoplasmic reticulum or Golgi involving the generation of disulfide bonds from two cysteine (Cys) residues and in the assembly of insect exoskeletons via the crosslinking of two tyrosine (Tyr) residues, or as a result of accidental exposure to oxidizing species (lowmolecular mass or enzymes) that chemically link two protein sites. These have been discussed elsewhere [8,9,10]
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