Structural and mechanistic mapping of a unique fumarate reductase

The 1.8 Angstrom resolution crystal structure of the tetraheme flavo-cytoch rome c(3), Fcc(3), provides the first mechanistic insight into respiratory fumarate reductases or succinate dehydrogenases. The multi-redox center, th ree-domain protein shows a 40 Angstrom long 'molecular wire' allowing rapid conduction of electrons through a new type of cytochrome domain onto the a ctive site flavin, driving the reduction of fumarate to succinate. In this structure a malate-like molecule is trapped in the enzyme active site. The interactions between this molecule and the enzyme suggest a clear mechanism for fumarate reduction in which the substrate is polarized and twisted, fa cilitating hydride transfer from the reduced flavin and subsequent: proton transfer, The enzyme active site in the oxidized form is completely buried at the interface between the flavin-binding and the clamp domains. Movement of the cytochrome and clamp domains is postulated to allow release of the product.