Background Cysteine and methionine will be the two sulfur containing proteins in protein. proteins. It could not be problematic for the majority of us to list the features of cysteine residues in protein. Well-known roles include antioxidant defense catalysis protein redox and structure sensing and regulation . In contrast we would have difficulty list the features of methionine (Met) residues apart from its well-known function in proteins initiation. Biochemistry text messages typically deal with Met being a universal hydrophobic amino acidity easily interchangeable with various other residues such as for example leucine or valine. This concept is outdated. During the last 15 years research from a number of laboratories NVP-AUY922 supports the concept that Met in proteins shares much of the same job description as cysteine playing important functions in oxidant defense redox sensing and regulation as well as protein structure. The most important common characteristic of cysteine and Met residues in proteins is usually that both are subject to reversible oxidation and reduction mediated either enzymatically or non-enzymatically. While cysteine forms cystine through a disulfide linkage Met forms methionine sulfoxide (MetO) by addition of oxygen to its sulfur atom. Disulfides may be reduced back to the thiol form by various reductases often utilizing NVP-AUY922 thioredoxin . MetO is NVP-AUY922 usually reduced EN-7 back to Met by the methionine sulfoxide reductases thioredoxin-dependent enzymes that are virtually universal among aerobic organisms [3 4 Oxidation of Met to MetO introduces a chiral center at the sulfur atom so there are two epimers of MetO; R-MetO and S-MetO. While an epimerase could theoretically exist that interconverts the forms none has been found so far. Instead organisms have two types of methionine sulfoxide reductases (Msr). MsrA specifically reduces S-MetO but not R-MetO. Conversely MsrB reduces R-MetO but not S-MetO. The presence of MsrA has been appreciated for decades while the NVP-AUY922 presence of MsrB was only reported recently . To date there is substantial experimental evidence to support the importance of MsrA both and    PC-12 cells  and human T cells . Interestingly overexpression in doubled the lifespan of the flies . Critical functions for MsrB remain to be defined given its more recent discovery. While cysteine is usually well-recognized for the ease of its oxidation it is often not valued that Met could be easily oxidized to MetO [15 16 Certainly the typical redox prospect of both electron reduced amount of dimethyl sulfoxide is certainly +160 mV  while that for cystine is certainly +220 mV . Cysteine is certainly conveniently oxidized when ionized to its thiolate but is certainly tough to oxidize when in the thiol type . Cysteine residues on the energetic sites of enzymes such as for example phosphatases dehydrogenases reductases and peroxidases generally possess a minimal pKa making them easily oxidizable . Nevertheless the most cysteine residues including those in glutathione possess a pKa around 8.3-8.7 and so are not easily oxidized in physiological pH unless the oxidation is catalyzed by an enzyme. On the other hand oxidation of Met residues is certainly indie of pH  essentially. . The comparative need for cysteine and Met as antioxidants is not established & most most likely varies with regards to the oxidizing agent. 2 Methionine residues in proteins as antioxidants 2.1 α2macroglobulin α2macroglobulin (A2M) is a higher molecular fat (~725 kDa) physiologically essential plasma proteinase inhibitor that goals a multitude NVP-AUY922 of proteinases [23 24 Performing within a “venus-flytrap”-like mode that acts to entrap proteinases within a molecular cage  A2M normally circulates being a homotetrameric molecule that’s disulfide linked right into a couple of dimers that are held in association by solid non-covalent forces. In its open up conformation focus on proteinases cleave an open “bait” region inside the A2M tetramer that creates the structural adjustments that bring about the irreversible entrapment from the protease. Frequently performing at sites of irritation where reactive air and NVP-AUY922 nitrogen types are at fairly high concentration it had been initially believed that A2M was resistant to oxidative adjustment . Tests by Weiss and co-workers However.