Coenzyme 5,10-methenyltetrahydrofolate

Flavins — Riboflavin is first of all essential as a vitamin for humans and animals. FAD and FMN are coenzymes for more than 150 enzymes. Most of them catalyze redox processes involving transfers of one or two electrons. In addition to these well known and documented functions, FAD is a co-factor of photolyases, enzymes that repair UV-induced lesions of DNA, acting as photoreactivating enzymes that use the blue light as an energy source to initiate the reaction. The active form of FAD in photolyases is their two-electron reduced form, and it is essential for binding to DNA and for catalysis. Photolyases contain a second co-factor, either 8-hydroxy-7,8-didemethyl-5-deazariboflavin or methenyltetrahydrofolate. ... 

The tetrahydrofolates do not function as tightly enzyme-bound coenzymes. Rather, they function as cosubstrates for a variety of enzymes associated with one-carbon metabolism. /Vl0-formyltetrahydrofolate is produced enzymatically from tetrahydrofolate and formate in an ATP-linked process in which formate is activated by phosphorylation to formyl phosphate the formyl group of formyl phosphate is then transferred to A10 of tetrahydrofolate. A10-Formyltetrahydrofolate is a formyl donor substrate for some enzymes and is interconvertible with A5,A10-methenyltetrahydrofolate by the action of cyclohydrolase. 

An example of direct repair is the photochemical cleavage of pyrimidine dimers. Nearly all cells contain a photoreactivating enzyme called DNA photolyase. The E. coli enzyme, a 35-kd protein that contains bound N lO-methenyltetrahydrofolate and flavin adenine dinucleotide cofactors, binds to the distorted region of DNA. The enzyme uses light energy—specifically, the absorption of a photon by the N, N lO-methenyltetrahydrofolate coenzyme—to form an excited state that cleaves the dimer into its original bases. 

Coenzyme 5,10-Methylene and Methenyltetrahydrofolate Models in Organic Synthesis... 

Coenzyme 5,10-methylene and methenyltetrahydrofolate models in organic s5mthesis 06AHC(91)159. 

The crystal structures of all photolyases revealed a globular shape and the presence of two coenzymes at a distance of 16.8 A and 17.5 A to each other, respectively. Every photolyase known today contains one FAD-cofactor bound in a cavity with the right dimension and polarity to also accommodate the DNA lesion. The architecture suggests that photolyases recognize the lesion substrate in a flipped out conformation. The second coenzyme, either a methenyltetrahydrofolate (MTHF) (Type-I photolyases) or a 5-deazaflavin (5-DF) (Type-II photolyase), depending on the type of photolyase, is bound in a shallow groove close to the surface of the protein (Figure 141.3). 

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