Editing Convergent evolution (section)

====Protease active sites====

The [[enzymology]] of [[proteases]] provides some of the clearest examples of convergent evolution. These examples reflect the intrinsic chemical constraints on enzymes, leading evolution to converge on equivalent solutions independently and repeatedly.<ref name="Buller&Townsend_2013"/><ref>{{cite journal |last=Dodson |first=G. |author2=Wlodawer, A. |title=Catalytic triads and their relatives |journal=Trends in Biochemical Sciences |date=September 1998 |volume=23 |issue=9 |pages=347–52 |pmid=9787641 |doi=10.1016/S0968-0004(98)01254-7}}</ref>

Serine and cysteine proteases use different amino acid functional groups (alcohol or thiol) as a [[nucleophile]]. To activate that nucleophile, they orient an acidic and a basic residue in a [[catalytic triad]]. The chemical and physical constraints on [[enzyme catalysis]] have caused identical triad arrangements to evolve independently more than 20 times in different [[enzyme superfamilies]].<ref name="Buller&Townsend_2013"/>

[[Threonine protease]]s use the amino acid threonine as their catalytic [[nucleophile]]. Unlike cysteine and serine, threonine is a [[secondary alcohol]] (i.e. has a methyl group). The methyl group of threonine greatly restricts the possible orientations of triad and substrate, as the methyl clashes with either the enzyme backbone or the histidine base. Consequently, most threonine proteases use an N-terminal threonine in order to avoid such [[steric clash]]es.
Several evolutionarily independent [[enzyme superfamilies]] with different [[protein fold]]s use the N-terminal residue as a nucleophile. This commonality of [[active site]] but difference of protein fold indicates that the active site evolved convergently in those families.<ref name="Buller&Townsend_2013"/><ref>{{cite journal |last1=Ekici |first1=O. D. |author2=Paetzel, M. |author3=Dalbey, R. E. |title=Unconventional serine proteases: variations on the catalytic Ser/His/Asp triad configuration |journal=Protein Science |date=December 2008 |volume=17 |issue=12 |pages=2023–37 |pmid=18824507 |doi=10.1110/ps.035436.108 |pmc=2590910}}</ref>