refers acid function centre active site acid base common motif generating form charge relay network activate attacks substrate forming intermediate free commonly acid occasionally fold complex dimensional structures far acid sequence primary structure brought close final fold evolution function best examples evolution chemical constraints led solution independently evolving separate mechanism action consequently best studied history 1930s identified modification 1950s structure solved ray 1960s showing orientation active site aligned reveal family related called family simultaneously structures unrelated found contain analogous charge relay mechanism activation members proposed late 1960s structures solved ray 1970s 80s analogous found classification system 1990s 2000s began structurally related acts database evolution understanding chemical constraints evolution led convergence families developed 2010s particular contention 1990s early 2000s contribution low barrier hydrogen bonding current thinking ordinary hydrogen bonding sufficient explain mechanism massive body work charge relay led mechanism best characterised function contain use reaction types split substrate transfer portion substrate second substrate inter dependent set active site act concert binding site hole achieve act member highly generating intermediate substrate resolved complete mechanism perform increased functional groups members oriented base bound acid performed stages activated attacks carbon forces oxygen accept electron leading intermediate build negative charge intermediate typically stabilized hole active site intermediate collapses half substrate leaving second half bound intermediate leaving group aided donation base second stage resolution intermediate attack second substrate substrate water result organic result transfer substrate attack second substrate forms new intermediate resolves releasing second product free identity members chain performs substrate lone pair present oxygen attacks carbon naturally occurring biological contain sufficiently functional groups difficult reactions increases efficient commonly alternatively use secondary chain extra group use terminal base separate acid use oxygen causes minor differences compared oxygen extra makes larger softer allows form longer bonds fold gives lower units dependent optimal orientation acid base members reduce order achieve low works disadvantage resolution intermediate reversal original attack favourable breakdown product base oriented leaving group ensure ejected leave bound substrate terminus finally resolution release substrate terminus requires leave forms longer bonds van der radius trapped active site base natural strongly base increase additionally product aid leaving group departure base commonly allows effective base hydrogen bonding acid use base high act acid state cycle use terminal base prevents close acid acidic member forms hydrogen bond basic basic restricting chain rotation positive charge acidic chains commonly member uses pair base usual acid second effective acid common leading lower efficiency acid member necessary act example uses member base act acid similarly virus contains ordered water position acid examples motif thoroughly characterised motifs exemplified model uses protein hydrogen increasing nitrogen allows act powerful general base activate hole consisting backbone charge build base aids leaving group water substrate remaining attacks intermediate evolved orientation members reversed additionally brain fold small protein found equivalent second studied motif families use set example acts similarly notable differences low importance varies effectively virus whilst begins non bonds uses acid base members removing acid results fold activity loss compared fold removed interpreted possible way generating active control rate unusual found low group means acts base low adaptation specific environments like acidic hot springs cell use secondary manner analogous use primary interference extra group base member terminal ordered water turn increase similarly exist equivalent configurations related use terminal base unusual occurs case acts middle middle forms strong hydrogen bonds activate chain backbone middle held unusual orientation facilitate precise contacts unusual act base performs role acid member making key structural contacts evolution active site network causes involved contact highly examples evolution reaction remains core active site adapted serve different functions reaction changes perform intermediate intermediate resolved water result substrate intermediate resolved attack second substrate acts example attack group results reaction families evolved adaptation exclude water favour attack second substrate additionally alternative mechanism evolved active sites active site substrate release free internal tunnel second active site transferred second substrate changes evolution active site slow strong chemical constraints evolved fold contains families use different switches occurred times evolutionary history mechanisms happen unclear contain mixture clan families designated evolution provides known examples evolution geometric arrangement occurs separate result evolution arrangement different structural fold limited productive ways arrange backbone substrate examples reflect chemical physical constraints leading evolution repeatedly independently converge equivalent solutions similar evolution occurred viral arrangement similarities mechanisms families families use acid unlike secondary group group greatly possible substrate clashes backbone base consequently located terminus independent different protein known use terminal fold fold active site structure completely different protein indicates active site evolved families
Catalytic triad