Abzyme

An abzyme[1] (from antibody and enzyme), also called catmab (from catalytic monoclonal antibody),[2] and most often called catalytic antibody or sometimes catab,[3] is a monoclonal antibody with catalytic activity. Abzymes are usually raised in lab animals immunized against synthetic haptens, but some natural abzymes can be found in normal humans (anti-vasoactive intestinal peptide autoantibodies) and in patients with autoimmune diseases such as systemic lupus erythematosus, where they can bind to and hydrolyze DNA.[1] To date abzymes display only weak, modest catalytic activity and have not proved to be of any practical use.[4] They are, however, subjects of considerable academic interest. Studying them has yielded important insights into reaction mechanisms, enzyme structure and function, catalysis, and the immune system itself.[4]

Enzymes function by lowering the activation energy of the transition state of a chemical reaction, thereby enabling the formation of an otherwise less-favorable molecular intermediate between the reactant(s) and the product(s). If an antibody is developed to bind to a molecule that is structurally and electronically similar to the transition state of a given chemical reaction, the developed antibody will bind to, and stabilize, the transition state, just like a natural enzyme, lowering the activation energy of the reaction, and thus catalyzing the reaction. By raising an antibody to bind to a stable transition-state analog, a new and unique type of enzyme is produced.

So far, all catalytic antibodies produced have displayed only modest, weak catalytic activity. The reasons for low catalytic activity for these molecules have been widely discussed. Possibilities indicate that factors beyond the binding site may play an important role, in particular through protein dynamics.[5] Some abzymes have been engineered to use metal ions and other cofactors to improve their catalytic activity.[6][7]

  1. ^ a b "Abzymes: Absource". crdd.osdd.net. Retrieved 2022-06-02.
  2. ^ "Study Notes on Abzymes (With Diagram)". Biology Discussion. 2016-02-24. Retrieved 2022-06-02.
  3. ^ Baron, D. (January 1992). "[Catalytic antibodies]". Die Naturwissenschaften. 79 (1): 15–22. doi:10.1007/BF01132273. ISSN 0028-1042. PMID 1552949. S2CID 39930319.
  4. ^ a b Barrera, G. J., Portillo, R., Mijares, A., Rocafull, M. A., del Castillo, J. R., & Thomas, L. E. (2009). Immunoglobulin A with protease activity secreted in human milk activates PAR-2 receptors, of intestinal epithelial cells HT-29, and promotes beta-defensin-2 expression. Immunology letters, 123(1), 52-59.
  5. ^ Agarwal PK (2005). "Role of protein dynamics in reaction rate enhancement by enzymes". J. Am. Chem. Soc. 127 (43): 15248–56. doi:10.1021/ja055251s. PMID 16248667.
  6. ^ Nicholas, Ken (January 30, 2004). "Catalytic Metalloantibodies: Biology in Service of Chemistry" (PDF). southeastern.edu. Archived (PDF) from the original on 2022-10-09. Retrieved 2019-11-11.
  7. ^ "Metalloantibodies. - Science - HighBeam Research". 23 March 2015. Archived from the original on 23 March 2015.