Editing Protease (section)

==Enzymatic function and mechanism==
[[File:Protease mechanism summary.svg|thumb|upright=2.4|A comparison of the two [[hydrolysis|hydrolytic]] mechanisms used for [[proteolysis]]. [[Enzyme]] is shown in black, [[Substrate (biochemistry)|substrate]] protein in red and [[water]] in blue. The top panel shows 1-step [[hydrolysis]] where the enzyme uses an [[acid]] to [[Chemical polarity|polarise]] water, which then hydrolyses the substrate. The bottom panel shows 2-step hydrolysis where a residue within the enzyme is activated to act as a [[nucleophile]] (Nu) and attack the substrate. This forms an intermediate where the enzyme is covalently linked to the N-terminal half of the substrate. In a second step, water is activated to hydrolyse this intermediate and complete catalysis. Other enzyme residues (not shown) donate and accept hydrogens and electrostatically stabilise charge build-up along the reaction mechanism.]]
{{see also|Catalytic triad}}
Proteases are involved in [[digestion|digesting]] long protein chains into shorter fragments by splitting the [[peptide bonds]] that link [[amino acid]] residues. Some detach the terminal amino acids from the protein chain ([[exopeptidases]], such as [[aminopeptidase]]s, [[carboxypeptidase A]]); others attack internal peptide bonds of a protein ([[endopeptidases]], such as [[trypsin]], [[chymotrypsin]], [[pepsin]], [[papain]], [[elastase]]).

===Catalysis===
[[Catalysis]] is achieved by one of two mechanisms:
*Aspartic, glutamic, and metallo-proteases activate a water molecule, which performs a nucleophilic attack on the peptide bond to hydrolyze it. 
*Serine, threonine, and cysteine proteases use a nucleophilic residue (usually in a [[catalytic triad]]). That residue performs a nucleophilic attack to [[covalent]]ly link the protease to the substrate protein, releasing the first half of the product. This covalent acyl-enzyme intermediate is then hydrolyzed by activated water to complete catalysis by releasing the second half of the product and regenerating the free enzyme

===Specificity===
Proteolysis can be highly [[enzyme promiscuity|promiscuous]] such that a wide range of protein substrates are hydrolyzed. This is the case for digestive enzymes such as [[trypsin]], which have to be able to cleave the array of proteins ingested into smaller peptide fragments. Promiscuous proteases typically bind to a single [[amino acid]] on the substrate and so only have specificity for that residue. For example, [[trypsin]] is specific for the sequences ...K\... or ...R\... ('\'=cleavage site).<ref>{{cite journal | vauthors = Rodriguez J, Gupta N, Smith RD, Pevzner PA | title = Does trypsin cut before proline? | journal = Journal of Proteome Research | volume = 7 | issue = 1 | pages = 300–305 | date = January 2008 | pmid = 18067249 | doi = 10.1021/pr0705035 }}</ref>

Conversely some proteases are highly specific and only cleave substrates with a certain sequence. Blood clotting (such as [[thrombin]]) and viral polyprotein processing (such as [[TEV protease]]) requires this level of specificity in order to achieve precise cleavage events. This is achieved by proteases having a long binding cleft or tunnel with several pockets that bind to specified residues. For example, [[TEV protease]] is specific for the sequence ...ENLYFQ\S... ('\'=cleavage site).<ref>{{cite journal | vauthors = Renicke C, Spadaccini R, Taxis C | title = A tobacco etch virus protease with increased substrate tolerance at the P1' position | journal = PLOS ONE | volume = 8 | issue = 6 | pages = e67915 | date = 2013-06-24 | pmid = 23826349 | pmc = 3691164 | doi = 10.1371/journal.pone.0067915 | doi-access = free | bibcode = 2013PLoSO...867915R }}</ref>

===Degradation and autolysis===
Proteases, being themselves proteins, are cleaved by other protease molecules, sometimes of the same variety. This acts as a method of regulation of protease activity. Some proteases are less active after autolysis (e.g. [[TEV protease]]) whilst others are more active (e.g. [[trypsinogen]]).