Liao DI, Wawrzak Z, Calabrese JC, Viitanen PV, Jordan DB (May 2001). "Crystal structure of riboflavin synthase". Structure 9 (5): 399–408
The first article I chose dealt with the overall structure of riboflavin synthase. The protein itself exists in a homotrimer form, and requires no additional cofactors to carry out its reaction. The enzyme is not typically found in humans, but it is very common in many bacteria. Each monomer contains two beta barrels and a C-terminal alpha helix. During the reaction, only one active site is available at a time. If you’re curious to see how awesome this structure really looks just check out my previous blog post.
Fischer M, Schott AK, Kemter K, Feicht R, Richter G, Illarionov B, Eisenreich W, Gerhardt S, Cushman M, Steinbacher S, Huber R, Bacher A (December 2003). "Riboflavin synthase of Schizosaccharomyces pombe. Protein dynamics revealed by 19F NMR protein perturbation experiments". BMC Biochem. 4: 18.
The second article I chose explained the mechanism of the reaction in good detail. The overall reaction done by riboflavin synthase is: (2) 6,7-dimethyl-8-ribityllumazine → riboflavin + 5-amino-6-ribitylamino-2,4(1H,3H)-pyrimidinedione. In this mechanism, a nucleophile is added to one molecule of 6,7-dimethyl-8-ribityllumazine, which then goes under nucleophilic attack. Two elimination reactions then occur and finally the intermediate aromatizes through another elimination reaction to yield the products. Overall, it is a quite complicated mechanism to understand. It is interesting to note here that this reaction can occur without the enzyme in boiling solution. However, bacteria need this enzyme to survive as they are unable to uptake riboflavin externally.
Cushman M, Yang D, Kis K, Bacher A (December 2001). "Design, synthesis, and evaluation of 9-D-ribityl-1,3,7-trihydro-2,6,8-purinetrione, a potent inhibitor of riboflavin synthase and lumazine synthase". J. Org. Chem. 66 (25): 8320–7.
The third article I chose discusses an inhibitor of riboflavin synthase. As mentioned before, bacteria are unable to take up riboflavin from their environment. With this in mind, scientist have realized that the ability to inhibit riboflavin synthase in bacteria would result in their destruction. You can imagine how useful this would be to kill off harmful gram-negative bacteria. The researchers in this article were able to design and synthesize a number of inhibitors with the most effective being: 9-D-Ribityl-1,3,7-trihydro-2,6,8-purinetrione. It is also important to note here that riboflavin synthase and lumazine synthase are often found in complex with one another as lumazine synthase recycles the pyrimidinedione product from riboflavin synthase. Many of these inhibitors found act on one or both of these enzymes.
