Mechanisms of flavoprotein-catalyzed reactions

Abstract

Flavoproteins are a class of enzymes catalyzing a very broad spectrum of redox processes by different chemical mechanisms. This review describes the best studied of these mechanisms and discusses factors possibly governing reactivity and specificity.A large number of flavin-containing enzymes, several hundreds, has been uncovered to date. An unusual feature of flavoproteins is the variety of the catalytic reactions performed, which range from typical redox catalysis such as the dehydrogenation of an amino acid, or the activation of dioxygen, to photochemistry; from 'DNA damage repair' to light emission. These few examples illustrate the fact that the same coenzyme is able to catalyze, or take part in catalytic events which must vary widely from a mechanistic point of view. The chemistry underlying the conversion itself will be quite different from case to case. This versatility sets flavoproteins apart from most other cofactor-dependent enzymes, which, in general, each catalyze a single type of chemical reaction. The activation or 'steering' of a particular activity of the flavin results from the interaction with the protein at the active center. On the other hand, for the vast majority of these enzymes a common feature exists, that at some stage during the catalytic event a transfer of electrons takes place between the substrate and the flavin itself.The purpose of the present review is not to enumerate the different functions of flavoproteins, this having been done elsewhere [l -41, but to focus on the mechanisms of catalysis, and on the possible ways of interaction of the flavin nucleus with the protein, i.e. on how this brings about chemistry appropriate to the particular enzyme reaction. In order toCorrespondence to S. Ghisla,

Functional Analysis of the Small Component of the 4-Hydroxyphenylacetate 3-Monooxygenase of Escherichia coli W: a Prototype of a New Flavin:NAD(P)H Reductase Subfamily

“…182, 2000 FLAVIN:NAD(P)H REDUCTASE OF E. COLI WFAD, and riboflavin with similar efficiencies but present a higher selectivity for NADH or NADPH (10,18,21,38). The low specificity could be ascribed to the fact that in these reductases, the flavin behaves as a real substrate and not as a tightly bound prosthetic group, as is the case in the majority of flavin enzymes (12). The HpaC oxidoreductase can also reduce cytochrome c and iron(III) at a high velocity (Table 1).…”

Covalent attachment of flavin adenine dinucleotide (FAD) and flavin mononucleotide (FMN) to enzymes: The current state of affairs

“…The data suggest that modulation by the protein environment of the histidyl group pKa in histidyl flavins could exert some control over the oxidationreduction potential of the flavin. Flavin is a versatile cofactor that has the potential to display many chemistries (Ghisla & Massey, 1989), and covalent incorporation may selectively enhance a reaction pathway and suppress unwanted side reactions. Within the context of this hypothesis, one needs to accommodate the finding that the same enzyme can be isolated as a covalent or noncovalent flavoprotein.…”

Crystal Structure and Site-directed Mutagenesis of 3-Ketosteroid Δ1-Dehydrogenase from Rhodococcus erythropolis SQ1 Explain Its Catalytic Mechanism

“…Catalytic Mechanism-The catalytic cycle of a typical flavoenzyme includes two half-reactions, i.e., a reductive half-reaction and an oxidative half-reaction (34). In the reductive halfreaction, the flavin coenzyme is reduced by a substrate, whereas in the oxidative half-reaction, the reduced coenzyme is reoxidized by an electron acceptor (34).…”