Pterins electron transfer between

While the evidence is undeniable for electron transfer via the pterin system for enzymes in the XO/XDH and AOR families, comparable structural features are not observed in SO. The additional electron-transfer group, the heme, is quite distant from the pterin ring system (Mo Fe 32 A) prohibiting an efficient electron transfer between these cofactors in the solid state. Because a flexible polypeptide chain connects the two domains housing the heme and the Moco, one postulation under investigation is that in solution the heme domain moves to position the heme closer to the pterin system to receive electrons during catalysis. 

Molybdopterin has another function besides participating in electron transfer between the site of catalysis and other electron-acceptor groups. It serves as an anchor for the active site where a multitude of hydrogen bonds between the pterin (and, if present, the dinucleotide) and the protein provide a secure tether for the reactive metal site (17). Evidence for the immobility conferred by the pterin(s) embedded in the protein is found in a comparsion of the DMSOR structures from both Rhodobacter sources. Regardless of the Mo coordination environment, the MGD ligands are nearly superimposable (75). This similarity of pterin structure is most clearly observed in the 1.3-A structure, where the Mo atom dissociated and shifted away from one pterin ligand, which otherwise was unaffected. The nucleotide tails on MGD, MCD, and other derivatives of molybdopterin also contribute to locking the molybdenum catalyst in position. 

Figure 2. The ligand common to all molybdenum and tungsten enzymes, MPT, is shown here in several formats (a) in common stick notation (b) as a ball and stick (c) an orientation rotated 90° from view (b) to emphasize the spacial relationship between the pterin plane and the dithiolene-pyran ring portion (d) MGD in common stick notation and for comparison, (e ) FAD, a common electron-transfer prosthetic group. Coordinates for the views in (b) and (c) are taken from the data deposited in the Protein Data Bank (PDB) for the 1.3-A resolution structure of DMSO reductase from Rhodobacter sphaeroides.

Figure 26. Electron-transfer pathway from the molybdenum-pterin center to EAD in xanthine oxidase. Besides the two mercapto groups. Mo is shown coordinated to inorganic sulfur and two oxygen atoms. The total distance between Mo and FAD is 2.9 nm. TTie redox eenters are coupled through a series of covalent bonds, three short van der Waals contacts, and a single hydrogen bond. Calculations were based on the Beratan and Onuchic model (6,7). Coordinates were taken from the PDB, code IFIQ. (See color insert.)...

On account of the requirement of NOS for tetrahy-drobiopterin, two general approaches toward a modulation of NOS activity seem feasible, manipulation of intracellular tetrahydrobiopterin levels and pterin-binding site antagonists. However, recombinant tetrahydrobiopterin-free NOS II catalysed the oxidation of four N-hydroxyguanidines tested by NADPH and O2, with formation of N02 and NOs" at rates between 20 and 80 nmol min" (mg of protein)" (Moali et al. 2001). In the case of N-(4-chlorophenyO-hT-hydroxyguanidine, formation of the corresponding urea and cyanamide was also detected besides that of N02" and NO3". These tetrahydrobiopterin-free NOS Il-dependent reactions were inhibited by modulators of electron transfer in NOS such as thiocitrulline or imidazole. 

The third recurring structural motif with non-amino-acid components found in metalloproteins is the metal-dithiolene unit found in molybdenum- and tungsten-containing oxidases or dehydrogenases (see Chapter 8.18). The dithiolene is typically a pterin derivative (often with phosphate and/or nucleotide appendages) and coordinated to Mo or W in a 1 1 or 2 1 stoichiometry (Figure 7)." These units usually function in two-electron redox reactions (cf 0x0 transfer ), shuttling between... 

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