Biosynthesis and processing of the molybdenum cofactors.

to each other, and define an electron-transfer pathway (Figure 1). Whereas the first Fe/S centre b is quite exposed to the solvent via its Cys-60, Fe/S centre a is buried approx. 15A below the molecular surface. The closest distance between the iron atoms of the two Fe/S centres is about lZA, and the molybdenum atom lies 1 S A away from the nearest iron atom of centre a. The molybdenum site is also buried but accessible to the protein surface through a deep tunnel as described. The bound inhibitory propan-2-01 in the inner compartment of the substrate-binding tunnel is a model for the Michaelis complex of the reaction of Mop with aldehydes (RCH=O) (Figure 2). The reaction is proposed to proceed by transfer of the molybdenum-bound water molecule as OH-, after proton transfer to Glu869, to the carbonyl group of the substrate, concertedly with hydride transfer to the sulphido group to generate: Mo'", =0, -SH, ---RCOO-. The dissociation of the carboxylic product may be facilitated by transient binding of Glu-869 to the molybdenum atom. The metalbound water is then replenished from a chain of structural internal water molecules. A second alcohol-binding site, located in a wider part of the tunnel (Figure l ) , may explain the strong substrate inhibition observed in Mop [S] as well as in xanthine oxidase [6]. This is also the putative binding site of large inhibitors of xanthine oxidase [7].