Cysteine protease 3710395 195627425 2008-03-03T20:18:02Z 192.117.113.122 +he {{Unreferenced|date=June 2007}} [[Image:L-cysteine-skeletal.png |thumb|100px|[[Cysteine]]]] [[Image:Cysteinprotease Reaktionsmechanismus.svg|thumb|300px|Reaction mechanism of the cysteine protease mediated cleavage of a peptide bond.]] [[Protease]]s are [[enzyme]]s that degrade [[protein|polypeptides]]. '''Cysteine proteases''' have a common catalytic mechanism that involves a [[nucleophile|nucleophilic]] [[cysteine]] [[thiol]] in a [[catalytic triad]]. The first step is deprotonation of a thiol in the enzyme's active site by an adjacent [[amino acid]] with a basic [[side chain]], usually a [[histidine]] residue. The next step is nucleophilic attack by the deprotonated cysteine's [[anion|anionic]] [[sulfur]] on the substrate [[carbonyl]] [[carbon]]. In this step, a fragment of the substrate is released with an [[amine]] terminus, the histidine residue in the protease is restored to its deprotonated form, and a [[thioester]] intermediate linking the new carboxy-terminus of the substrate to the cysteine thiol is formed. The thioester bond is subsequently hydrolyzed to generate a [[carboxylic acid]] moiety on the remaining substrate fragment, while regenerating the free enzyme. ==Examples of Cysteine Proteases== * [[Papain]] * [[Cathepsins]] * [[Caspases]] * [[Calpains]] ==Protease Regulation== Proteases are usually synthesized as large precursor proteins called [[zymogens]], such as the [[serine protease]] precursors [[trypsinogen]] and [[chymotrypsinogen]], and the [[aspartic protease]] precursor [[pepsinogen]]. The protease is activated by removal of an inhibitory segment or protein. Activation occurs once the protease is delivered to a specific intracellular compartment (e.g. [[lysosome]]) or extracellular environment (e.g. [[stomach]]). This system prevents the [[cell (biology)|cell]] that produces the protease from being damaged by it. Protease [[Enzyme inhibitor|inhibitor]]s are usually proteins with [[structural domain|domain]]s that enter or block a protease [[active site]] to prevent [[Substrate (biochemistry)|substrate]] access. In [[competitive inhibitor|competitive inhibition]], the inhibitor binds to the active site, thus preventing enzyme-substrate interaction. In [[competitive inhibitor|non-competitive inhibition]], the inhibitor binds to an [[allosteric regulation|allosteric site]], which alters the active site and makes it inaccessible to the substrate. ==Examples of Protease Inhibitors== * [[Serpin]]s * [[Stefin]]s * [[Inhibitor of apoptosis|IAP]]s * [[TIMP]]s ==External links== * {{MeshName|Cysteine+endopeptidases}} {{Proteases}} {{Cysteine proteases}} [[Category:EC 3.4.22|*]] [[de:Cysteinprotease]] [[fr:cystéine protéase]] [[he:ציסטאין פרוטאז]]