Catalytic triad

The enzyme TEV protease[a] contains an example of a catalytic triad of residues (red) in its active site. The triad consists of an aspartate (acid), histidine (base) and cysteine (nucleophile). The substrate (black) is bound by the binding site to orient it next to the triad. (PDB: 1LVM​)

A catalytic triad is a set of three coordinated amino acids that can be found in the active site of some enzymes.[1][2] Catalytic triads are most commonly found in hydrolase and transferase enzymes (e.g. proteases, amidases, esterases, acylases, lipases and β-lactamases). An acid-base-nucleophile triad is a common motif for generating a nucleophilic residue for covalent catalysis. The residues form a charge-relay network to polarise and activate the nucleophile, which attacks the substrate, forming a covalent intermediate which is then hydrolysed to release the product and regenerate free enzyme. The nucleophile is most commonly a serine or cysteine amino acid, but occasionally threonine or even selenocysteine. The 3D structure of the enzyme brings together the triad residues in a precise orientation, even though they may be far apart in the sequence (primary structure).[3]

As well as divergent evolution of function (and even the triad's nucleophile), catalytic triads show some of the best examples of convergent evolution. Chemical constraints on catalysis have led to the same catalytic solution independently evolving in at least 23 separate superfamilies.[2] Their mechanism of action is consequently one of the best studied in biochemistry.[4][5]


Cite error: There are <ref group=lower-alpha> tags or {{efn}} templates on this page, but the references will not show without a {{reflist|group=lower-alpha}} template or {{notelist}} template (see the help page).

  1. ^ Cite error: The named reference :2 was invoked but never defined (see the help page).
  2. ^ a b Buller AR, Townsend CA (2013). "Intrinsic evolutionary constraints on protease structure, enzyme acylation, and the identity of the catalytic triad". Proc. Natl. Acad. Sci. U.S.A. 110 (8): E653–61. Bibcode:2013PNAS..110E.653B. doi:10.1073/pnas.1221050110. PMC 3581919. PMID 23382230.
  3. ^ Stryer L, Berg JM, Tymoczko JL (2002). "9 Catalytic Strategies". Biochemistry (5th ed.). San Francisco: W.H. Freeman. ISBN 9780716749554.
  4. ^ Perutz M (1992). Protein structure. New approaches to disease and therapy. New York: W.H. Freeman and Co. ISBN 9780716770213.
  5. ^ Neurath H (1994). "Proteolytic enzymes past and present: the second golden era. Recollections, special section in honor of Max Perutz". Protein Sci. 3 (10): 1734–9. doi:10.1002/pro.5560031013. PMC 2142620. PMID 7849591.