Pterin-molybdenum redox

Pterin-Molybdenum Redox Chemistry. The early studies focused on Mo(vi) and tetrahydropterin reagents to closely mimic the Mo and pterin portions of Moco. These studies showed that a variety of dioxo-Mo(vi) complexes reacted with tetrahydropterins to produce intensely colored mono-0x0 Mo complexes, but the reports offered different interpretations of what reaction had occurred and what resulting oxidation states of molybdenum and pterin had been produced, even when X-ray structures of the product Mo-pterin complexes were available. A clear picture of the electronic structure was eventually developed from redox titrations, reactivity studies, theoretical calculations and X-ray photoelectron spectroscopy (XPS) studies. 

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. 

In summary, we may add that bacterial utilization of quinoline and its derivatives as a rule depends on the availability of traces of molybdate in the culture medium [363], In contrast, growth of the bacterial strains on the first intermediate of each catabolic pathway, namely, the lH-2-oxo or 1 II-4-oxo derivatives of the quinoline compound was not affected by the availability of molybdate. This observation indicated a possible role of the trace element molybdenum in the initial hydroxylation at C2. In enzymes, Mo occurs as part of the redox-active co-factor, and all the Mo-enzymes involved in N-heteroatomic compound metabolism, contain a pterin Mo co-factor. The catalyzed reaction involves the transfer of an oxygen atom to or from a substrate molecule in a two-electron redox reaction. The oxygen is supplied by the aqueous solvent. Certainly, the Mo-enzymes play an important role in the initial steps of N-containing heterocycles degradation. 

DNA cleavage by, 43 158-159 reactions, copper proteins, 39 25 Oxo-trichloroselenates(IV), 35 270-271 Oxo-type molybdenum enzyme, see Molybdenum enzymes, pterin-containing Oxovandium (IV), solvent exchange and ligand substitution, 42 47-49 Oxyanions, Groups VIB and VIIB, redox reactions, kinetics and mechanism, 40 269-274... 

Three human redox enzymes, and a variety of bacterial enzymes, contain molybdenum chelated by two sulfur atoms in a modified pterin molybdopterin (see Figure 10.1). In sulfite oxidase, the other two chelation sites of the molybdenum are occupied by oxygen in xanthine oxidase / dehydrogenase (Section 7.3.7) and aldehyde oxidase, one site is occupied by oxygen and one by sulfur. In some bacterial enzymes, molybdopterin occurs as a guanine dinucleotide rather than free. In others, tungsten rather than molybdopterin is the chelated metal there is no evidence that any mammalian enzymes contain tungsten. 

Molybdenum hydroxylases (i.e., AO and XO) are flavoproteins that contain in addition to a FAD, a pterine cofactor coordinated to a molybdenum atom, and an iron sulfur center for their catalytic activity. They catalyze the two-electron oxidation of substrates with transfer to molecular oxygen to produce H2O2, and insert an atom of oxygen from water into a wide range of N-hctcrocycies and aldehydes via two-electron redox reaction as shown in equation 1.4 ... 

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 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... 

The molybdenum cofactor (Moco) is an extraordinary molecule in biology. As a small metal-containing compound, it has the unprecedented combination of a dithiolene chelate for metal binding and a pterin appended to a pyran ring. The resultant cofactor is electronically nimble due to the presence of three redox active moieties, ie. the molybdenum atom, the dithiolene and the pterin, which in concert can support a range of redox events. 

Subsequent Mo-pterin model investigations addressed a seeond provocative aspeet of Rajagopalan s proposed Moeo strueture. The 1982 proposal for Moco paired an oxidized Mo center with a redueed tetrahydropterin - a juxtaposition of the highest molybdenum oxidation state with the most reduced form of pterin - that seemed incompatible and implied possible redox reactions between the metal and the organie eofactor. This seetion deseribes studies direeted at exploring whether molybdenum and pterin redox reactions might occur. These studies were conducted from 1989 to 1999 and inelude reactivity studies of oxidized molybdenum(vi) with redueed pterins, and studies of redueed molybdenum(iv) with oxidized pterins and pteridines. 

The second method of establishing oxidation states employed redox titration using the redox dye dichlorophenolindophenol (DCIP) based on the knowledge that tetrahydropterins reduce DCIP instantaneously while qui-nonoid dihydropterins react slowly and 7,8-dihydropterins do not reduce DCIP at all. As previously mentioned in this chapter, DCIP oxidation of Moeo within several molybdoenzymes was determined to be a two-electron process, suggesting a dihydropterin reduction state that was speculated to be the quinonoid tautomer. The results of stoichiometric additions of DCIP to the molybdenum complexes of reduced pterins showed that no oxidation of... 

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