Editing Abzyme

{{Short description|Type of antibody}}
An '''abzyme'''<ref name=":0">{{Cite web |title=Abzymes: Absource |url=http://crdd.osdd.net/raghava/absource/abzyme.html |access-date=2022-06-02 |website=crdd.osdd.net}}</ref> (from [[antibody]] and [[enzyme]]), also called '''catmab''' (from '''catalytic monoclonal antibody'''),<ref>{{Cite web |date=2016-02-24 |title=Study Notes on Abzymes (With Diagram) |url=https://www.biologydiscussion.com/enzymes/study-notes-on-abzymes-with-diagram/22960 |access-date=2022-06-02 |website=Biology Discussion |language=en-US}}</ref> and most often called '''catalytic antibody''' or sometimes '''catab''',<ref>{{Cite journal |last=Baron |first=D. |date=January 1992 |title=[Catalytic antibodies] |url=https://pubmed.ncbi.nlm.nih.gov/1552949/ |journal=Die Naturwissenschaften |volume=79 |issue=1 |pages=15–22 |doi=10.1007/BF01132273 |issn=0028-1042 |pmid=1552949|s2cid=39930319 }}</ref> is a [[monoclonal antibody]] with [[catalytic activity]]. Abzymes are usually raised in [[lab animal]]s 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]].<ref name=":0" /> To date abzymes display only weak, modest catalytic activity and have not proved to be of any practical use.<ref name="Barrera 2009">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.</ref> 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.<ref name="Barrera 2009" />

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.<ref>{{cite journal |author=Agarwal PK |title=Role of protein dynamics in reaction rate enhancement by enzymes |journal=J. Am. Chem. Soc. |volume=127 |issue=43 |pages=15248–56 |year=2005 |pmid=16248667 |doi=10.1021/ja055251s}}</ref> Some abzymes have been engineered to use metal ions and other [[cofactor (biochemistry)|cofactor]]s to improve their catalytic activity.<ref>{{cite web|url=http://www2.southeastern.edu/Academics/Faculty/dnorwood/oldseminars/spring04/SeminarNicholas.pdf |archive-url=https://ghostarchive.org/archive/20221009/http://www2.southeastern.edu/Academics/Faculty/dnorwood/oldseminars/spring04/SeminarNicholas.pdf |archive-date=2022-10-09 |url-status=live |title=Catalytic Metalloantibodies: Biology in Service of Chemistry |last=Nicholas |first=Ken |publisher=southeastern.edu |date=January 30, 2004 |access-date=2019-11-11}}</ref><ref>{{cite web|url=http://www.highbeam.com/doc/1G1-9343909.html|archive-url=https://web.archive.org/web/20150323011733/http://www.highbeam.com/doc/1G1-9343909.html|url-status=dead|archive-date=23 March 2015|title=Metalloantibodies. - Science - HighBeam Research|date=23 March 2015}}</ref>

==History==

The possibility of catalyzing a reaction by means of an antibody which binds the transition state was first suggested by [[William Jencks|William P. Jencks]] in 1969.<ref>{{cite web|url=http://www.dsch.univ.trieste.it/~benedetti/antibody_catalysis.htm|title=Antibody Catalysis, Linus Pauling, W.P. Jencks, Kohler and Milstein|website=www.dsch.univ.trieste.it}}</ref> In 1994 [[Peter G. Schultz]] and [[Richard A. Lerner]] received the prestigious [[Wolf Prize in Chemistry]] for developing catalytic antibodies for many reactions and popularizing their study into a significant sub-field of enzymology.<ref>{{cite web|url=https://www2.lbl.gov/Science-Articles/Archive/Peter-Schultz-Wolf-Prize.html|title=Organic Chemist Peter Schultz wins Wolf Prize in Chemistry|website=www2.lbl.gov}}</ref>

==Abzymes in healthy human breast milk==
There are a broad range of abzymes in healthy human breast milk with DNAse, RNAse, and protease activity.<ref name="Barrera 2009" />

==Potential HIV treatment==

In a June 2008 issue of the journal Autoimmunity Review,<ref>{{Cite journal | pmid = 18558365| year = 2008| last1 = Planque| first1 = S| title = Catalytic antibodies to HIV: Physiological role and potential clinical utility| journal = Autoimmunity Reviews| volume = 7| issue = 6| pages = 473–9| last2 = Nishiyama| first2 = Y| last3 = Taguchi| first3 = H| last4 = Salas| first4 = M| last5 = Hanson| first5 = C| last6 = Paul| first6 = S| doi = 10.1016/j.autrev.2008.04.002| pmc = 2527403}}</ref><ref name="physorg">{{cite web |url=http://www.physorg.com/news135360794.html |title=UT pathologists believe they have pinpointed Achilles heel of HIV |work=physorg.com |access-date=2008-07-16}}</ref> researchers S. Planque, Sudhir Paul, Ph.D., and Yasuhiro Nishiyama, Ph.D. of the University Of Texas Medical School at Houston announced that they have engineered an abzyme that degrades the superantigenic region of the [[gp120]] [[CD4]] binding site. This is the one part of the [[HIV]] [[virus]] outer coating that does not change, because it is the attachment point to [[T lymphocytes]], the key cell in [[cell-mediated immunity]]. Once infected by HIV, patients produce antibodies to the more changeable parts of the viral coat. The antibodies are ineffective because of the virus' ability to change their coats rapidly. Because this protein gp120 is necessary for HIV to attach, it does not change across different strains and is a point of vulnerability across the entire range of the HIV variant population.

The abzyme does more than bind to the site: it catalytically destroys the site, rendering the virus inert, and then can attack other HIV viruses. A single abzyme molecule can destroy thousands of HIV viruses.

==References==
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{{HIVpharm}}

[[Category:Monoclonal antibodies]]
[[Category:Immune system]]
[[Category:Enzymes]]