This web page was produced as an assignment for Genetics 677, an undergraduate course at UW-Madison.
Small Molecule Interactions
As discussed on the Home Page Crohn's Disease in humans is primarily associated with inactive NOD2. In a search of bioassays using
PubChem, no compounds were found which increased NOD2 activity but 3 compounds were identified which inhibit normal NOD2. These three chemicals, CID3238219, CID653676, and SID87225496 are shown below
Analysis
Because NOD2 has lowered activity in most cases of human Crohn's Disease, one option for treatment would be a compound which increases NOD2 activity. Unfortunately no such compounds were identified. Because the above compounds all inhibit NOD2 activity, they could be used to generate chemically induced Crohn's Disease-like symptoms for study. In mice it has been implicated that NOD2 gain of function mutations are responsible for some Crohn's disease cases. In these instances such compounds may prove useful in treatment provide that they are administered early on in disease progression [2]. It is also worth noting here that, as discussed on the protein domain page, the LRR domain of NOD2 naturally recognizes the small molecule muramyl dipeptide(MDP) and undergoes a conformational change which allows it to oligomerize and become active. This is the key first step in bacterial recognition, as MDP is a bi-product of bacterial cell wall production. A depiction of this interaction is shown below. A thorough structural study of MDP-NOD2 interaction may provide insights into Crohn's Disease.
References
[1]
PubChem
[2] Vignal, Cecile, Elisabeth Singer, Laurent Peyrin-Biroulet, Pierre Desreumaux, and Mathias Chamaillard. "How NOD2 Mutations Predispose to Crohn's Disease?" Microbes and Infection 9.5 (2007): 658-63. Print.
[3] Carneiro LA, Travassos LH, Philpott DJ. Innate immune recognition of microbes through Nod1 and Nod2: implications for disease. Microbes Infect. 2004;6(6):609-16.
[2] Vignal, Cecile, Elisabeth Singer, Laurent Peyrin-Biroulet, Pierre Desreumaux, and Mathias Chamaillard. "How NOD2 Mutations Predispose to Crohn's Disease?" Microbes and Infection 9.5 (2007): 658-63. Print.
[3] Carneiro LA, Travassos LH, Philpott DJ. Innate immune recognition of microbes through Nod1 and Nod2: implications for disease. Microbes Infect. 2004;6(6):609-16.