Pterins centers

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.)...

The aldehyde oxidoreductase from Desulfovibrio gigas shows 52% sequence identity with xanthine oxidase (199, 212) and is, so far, the single representative of the xanthine oxidase family. The 3D structure of MOP was analyzed at 1.8 A resolution in several states oxidized, reduced, desulfo and sulfo forms, and alcohol-bound (200), which has allowed more precise definition of the metal coordination site and contributed to the understanding of its role in catalysis. The overall structure, composed of a single polypeptide of 907 amino acid residues, is organized into four domains two N-terminus smaller domains, which bind the two types of [2Fe-2S] centers and two much larger domains, which harbor the molybdopterin cofactor, deeply buried in the molecule (Fig. 10). The pterin cofactor is present as a cytosine dinucleotide (MCD) and is 15 A away from the molecular surface,... 

D. desulfuricans is able to grow on nitrate, inducing two enzymes that responsible for the steps of conversion of nitrate to nitrite (nitrate reductase-NAP), which is an iron-sulfur Mo-containing enzyme, and that for conversion of nitrite to ammonia (nitrite reduc-tase-NIR), which is a heme-containing enzyme. Nitrate reductase from D. desulfuricans is the only characterized enzyme isolated from a sulfate reducer that has this function. The enzyme is a monomer of 74 kDa and contains two MGD bound to a molybdenum and one [4Fe-4S] center (228, 229) in a single polypeptide chain of 753 amino acids. FXAFS data on the native nitrate reductase show that besides the two pterins coordinated to the molybdenum, there is a cysteine and a nonsulfur ligand, probably a Mo-OH (G. N. George, personal communication). 

In the first family, the metal is coordinated by one molecule of the pterin cofactor, while in the second, it is coordinated to two pterin molecules (both in the guanine dinucleotide form, with the two dinucleotides extending from the active site in opposite directions). Some enzymes also contain FejSj clusters (one or more), which do not seem to be directly linked to the Mo centers. The molybdenum hydroxylases invariably possess redox-active sites in addition to the molybdenum center and are found with two basic types of polypeptide architecture. The enzymes metabolizing quinoline-related compounds, and derivatives of nicotinic acid form a separate groups, in which each of the redox active centers are found in separate subunits. Those enzymes possessing flavin subunits are organized as a2jS2A2, with a pair of 2Fe-2S centers in the (3 subunit, the flavin in the (3 subunit, and the molybdenum in the y subunit. 

Fe 2S], a [4Fe-4S] and a [3Fe-4S] center. The enzyme catalyzes the reversible redox conversion of succinate to fumarate. Voltammetry of the enzyme on PGE electrodes in the presence of fumarate shows a catalytic wave for the reduction of fumarate to succinate (much more current than could be accounted for by the stoichiometric reduction of the protein active sites). Typical catalytic waves have a sigmoidal shape at a rotating disk electrode, but in the case of succinate dehydrogenase the catalytic wave shows a definite peak. This window of optimal potential for electrocatalysis seems to be a consequence of having multiple redox sites within the enzyme. Similar results were obtained with DMSO reductase, which contains a Mo-bis(pterin) active site and four [4Fe 4S] centers. 

Raman, C. S., Li, H., Martasek, P., Kral, V., Masters, B. S., Poulos, T. L., Crystal structure of constitutive endothelial nitric oxide synthase a paradigm for pterin function involving a novel metal center, Cell 95 (1998),... 

It was originally hypothesized that one role of the Zn center is to help form and stabilize the pterin binding site (81). As shown in Fig. 4, the conserved Serl04, which is only three residues from one Zn ligand, directly H-bonds to the pterin. A disruption of the Zn site should, therefore, perturb interactions at the pterin site. A direct comparison between the Zn-bound and disulfide forms supports this hypothesis. In order to form the S—S bond, the entire section of polypeptide involving Serl04 must slide down and away from the pterin site, which... 

Some compounds of this type may have a high affinity for proteins that is not due to their binding to two thiol groups (35). In particular, arsenite also reacts with the molybdenum-pterin cofactor of many enzymes (35a-d). This usually inhibits the enzyme, but in particular cases (35e) the arsenite may be oxidized indeed the enzyme arsenite oxidase contains such a center (35f). 

Both biopterin (30) and neopterin (31) belong to the family of naturally occurring 6-hydroxypropylpterin and are isolated as major pterins from almost all higher animals. Due to the existence of 2 chiral centers on the propyl side chain, 4 diastereomers are possible in biopterin and neopterin, and isomers 32-37 are found and considered to be minor or exceptional pterins. The absolute configurations of biopterin and neopterin are R,2 S and l S,2 R, respectively, and expedient notations of L-erytho, for biopterin, and d-erythro, for neopterin, have frequently been used. Following these notations, the di-... 

Figure 20 Proposed roles of the iron center and the pterin cofactor in the oxygen activation mechanism for pterin-dependent hydroxylases.

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