Editing Protease (section)

==Classification==

===Based on catalytic residue===
{{See also|Catalytic residue}}
Proteases can be classified into seven broad groups:<ref>{{cite journal | vauthors = Oda K | title = New families of carboxyl peptidases: serine-carboxyl peptidases and glutamic peptidases | journal = Journal of Biochemistry | volume = 151 | issue = 1 | pages = 13–25 | date = January 2012 | pmid = 22016395 | doi = 10.1093/jb/mvr129 | name-list-style = vanc | doi-access = free }}</ref>
* [[Serine protease]]s - using a [[serine]] [[Alcohol (chemistry)|alcohol]]
* [[Cysteine protease]]s - using a [[cysteine]] [[thiol]]
* [[Threonine protease]]s - using a [[threonine]] [[secondary alcohol]]
* [[Aspartic protease]]s - using an [[Aspartic acid|aspartate]] [[carboxylic acid]]
* [[Glutamic protease]]s - using a [[Glutamic acid|glutamate]] [[carboxylic acid]]
* [[Metalloprotease]]s - using a [[metal]], usually [[zinc]]<ref name="King 996–1007"/><ref name="Shen 870–874"/>
* [[Asparagine peptide lyases]] - using an [[asparagine]] to perform an [[elimination reaction]] (not requiring water)

Proteases were first grouped into 84 families according to their evolutionary relationship in 1993, and classified under four catalytic types: [[Serine protease|serine]], [[Cysteine protease|cysteine]], [[Aspartic protease|aspartic]], and [[Metalloprotease|metallo]] proteases.<ref>{{cite journal | vauthors = Rawlings ND, Barrett AJ | title = Evolutionary families of peptidases | journal = The Biochemical Journal | volume = 290 | issue = Pt 1 | pages = 205–218 | date = February 1993 | pmid = 8439290 | pmc = 1132403 | doi = 10.1042/bj2900205 }}</ref>  The [[Threonine protease|threonine]] and [[Glutamic protease|glutamic]] proteases were not described until 1995 and 2004 respectively. The mechanism used to cleave a [[peptide bond]] involves making an [[amino acid]] residue that has the cysteine and threonine (proteases) or a water molecule (aspartic, glutamic and metalloproteases) nucleophilic so that it can attack the peptide [[carbonyl]] group. One way to make a [[nucleophile]] is by a [[catalytic triad]], where a [[histidine]] residue is used to activate [[serine]], [[cysteine]], or [[threonine]] as a nucleophile. This is not an evolutionary grouping, however, as the nucleophile types have [[catalytic triad|evolved convergently]] in different [[protein superfamily|superfamilies]], and some superfamilies show divergent evolution to multiple different nucleophiles. Metalloproteases, aspartic, and glutamic proteases utilize their active site residues to activate a water molecule, which then attacks the scissile bond.<ref>{{cite journal |first1=Laura E. |last1=Sanman |title=Activity-Based Profiling of Proteases |journal=Annual Review of Biochemistry |date=June 2014 |volume=83 |pages=249–273 |doi=10.1146/annurev-biochem-060713-035352 |pmid=24905783 |url=https://doi.org/10.1146/annurev-biochem-060713-035352}}</ref>

==== Peptide lyases ====
A seventh catalytic type of proteolytic enzymes, [[asparagine peptide lyase]], was described in 2011. Its proteolytic mechanism is unusual since, rather than [[hydrolysis]], it performs an [[elimination reaction]].<ref name=":0">{{cite journal | vauthors = Rawlings ND, Barrett AJ, Bateman A | title = Asparagine peptide lyases: a seventh catalytic type of proteolytic enzymes | journal = The Journal of Biological Chemistry | volume = 286 | issue = 44 | pages = 38321–38328 | date = November 2011 | pmid = 21832066 | pmc = 3207474 | doi = 10.1074/jbc.M111.260026 | doi-access = free }}</ref> During this reaction, the catalytic [[asparagine]] forms a cyclic chemical structure that cleaves itself at asparagine residues in proteins under the right conditions. Given its fundamentally different mechanism, its inclusion as a peptidase may be debatable.<ref name=":0"/>

===Based on evolutionary phylogeny===
An up-to-date classification of protease evolutionary [[protein superfamily|superfamilies]] is found in the MEROPS database.<ref name="pmid19892822">{{cite journal | vauthors = Rawlings ND, Barrett AJ, Bateman A | title = MEROPS: the peptidase database | journal = Nucleic Acids Research | volume = 38 | issue = Database issue | pages = D227–D233 | date = January 2010 | pmid = 19892822 | pmc = 2808883 | doi = 10.1093/nar/gkp971 }}</ref> In this database, proteases are classified firstly by 'clan' ([[protein superfamily|superfamily]]) based on structure, mechanism and catalytic residue order (e.g. the [[PA clan]] where P indicates a mixture of nucleophile families). Within each 'clan', proteases are classified into [[protein family|families]] based on sequence similarity (e.g. the S1 and C3 families within the PA clan). Each family may contain many hundreds of related proteases (e.g. [[trypsin]], [[elastase]], [[thrombin]] and [[Streptogrisin A|streptogrisin]] within the S1 family).

Currently more than 50 clans are known, each indicating an independent evolutionary origin of proteolysis.<ref name="pmid19892822" />

===Based on optimal pH===
Alternatively, proteases may be classified by the optimal [[pH]] in which they are active:

*''Acid proteases''
*''Neutral proteases'' involved in [[type 1 hypersensitivity]]. Here, it is released by [[mast cell]]s and causes activation of [[complement system|complement]] and [[kinins]].<ref name=Kumar122>{{cite book | last1 = Mitchell | first1 = Richard Sheppard | last2 = Kumar | first2 = Vinay | last3 = Abbas | first3 = Abul K. | last4 = Fausto | first4 = Nelson | name-list-style = vanc |title=Robbins Basic Pathology |publisher=Saunders |location=Philadelphia |year= 2007|pages=122 |isbn=978-1-4160-2973-1 | edition = 8th }}</ref> This group includes the [[calpains]].
*''[[Basic proteases]]'' (or ''alkaline proteases'')