Pterins structure

The natural cofactor of the AAHs, BH4 (Scheme 2), is a heterocyclic compound chemically classified as a pteridine that includes a fused pyrimidine and pyrazine rings. As many other naturally occurring pteridines BH4 has a pterin structure, which includes an amino substituent in position 2 and an oxo group in position 4 of the pyrimidine ring. The term biopterin is reserved for pterins with a dihydroxypropyl group in position 6. 

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. 

Pterin, 4-amino — see Folic acid, 4-amino-4-deoxy-Pterin, 6-amino-structure, 3, 276 Pterin, 7-amino-structure, 3, 276 Pterin, 6-arylthio-reactivity, 3, 299 Pterin, 6-(l-carboxyethoxy)-synthesis, 3, 309 Pterin, 6-carboxy-7-hydroxy-properties, 3, 277 Pterin, 7-carboxy-6-hydroxy-properties, 3, 277 Pterin, 6-chloro-nucleophilic substitution, 3, 292 synthesis, 3, 290... 

Pterin, 5-formyl-6,7-dimethyl-5,6,7,8-tetrahydro-structure, 3, 281 Pterin, 6-hydroxymethyl-reactions, 3, 304 structure, 3, 273 Pterin, 7-hydroxymethyl-synthesis, 3, 311... 

Pterin, 8-methyl-synthesis, 3, 305 Pterin, 6-methyl-7,8-dihydro-hydrochloride structure, 3, 279... 

FIGURE 18.35 Formation of THF from folic acid by the dihydrofolate reductase reaction. The R group on these folate molecules symbolizes the one to seven (or more) glutamate units that folates characteristically contain. All of these glutamates are bound in y-carboxyl amide linkages (as in the folic acid structure shown in the box A Deeper Look Folic Acid, Pterins, and Insect VFingis). The one-carbon units carried by THF are bound at N, or at or as a single carbon attached to both... 

The molyhdopterin cofactor, as found in different enzymes, may be present either as the nucleoside monophosphate or in the dinucleotide form. In some cases the molybdenum atom binds one single cofactor molecule, while in others, two pterin cofactors coordinate the metal. Molyhdopterin cytosine dinucleotide (MCD) is found in AORs from sulfate reducers, and molyhdopterin adenine dinucleotide and molyb-dopterin hypoxanthine dinucleotide were reported for other enzymes (205). The first structural evidence for binding of the dithiolene group of the pterin tricyclic system to molybdenum was shown for the AOR from Pyrococcus furiosus and D. gigas (199). In the latter, one molyb-dopterin cytosine dinucleotide (MCD) is used for molybdenum ligation. Two molecules of MGD are present in the formate dehydrogenase and nitrate reductase. 

D. gigas AOR was the first Mo-pterin-containing protein whose 3D structure was solved. From D. desulfuricans, a homologous AOR (MOD) was purified, characterized, and crystallized. Both proteins are homodimers with-100 kDa subunits and contain one Mo-pterin site (MCD-cofactor) and two [2Fe-2S] clusters. Flavin moieties are not found. The visible absorption spectrum of the proteins (absorption wavelengths, extinction coefficients, and optical ratios at characteristic wavelengths) are similar to those observed for the deflavo-forms of... 

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,... 

Purines absorb only ultraviolet light and they contribute to structural colors (white and silver) in animals. Pterines are generally yellow, orange, or red pigments. Because they are amphoteric molecules, the absorption spectra depend on the pH and present three or two absorption maxima, usually one in the visible region. Sepiapterin has an absorption maximum at 340 nm in O.IM NaOH and at 410 nm in O.IM HCl." Leucopterin has three maxima 240, 285, and 340 nm. Xanthopterin has two 255 and 391 nm. Because they are conjugated with proteins, pterins show bathochromic shifts in vivo. They also present fluorescence when excited with UV light. 

FIGURE 10.10 Structural formula of folic acid and related compounds. 1 — [3, 5, 7,9- H]folic acid (boldfaced letter H denotes radioactivity), 2 — pterine-6-carboxylic acid, 3 — /)-aminobenzoyl-L-glutamic acid. 

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