Pterin group

The carboxypeptidase family of enz5Tnes also includes carboxypeptidase G2 (CPG2) which catalyses the cleavage of C-terminal glutamate from folate (28.24) and related compounds such as methotrexate (in which NH2 replaces the OH group in the pterin group, and NMe replaces NH in the 4-amino benzoic acid unit). 

AT-Oxidation is very sensitive to steric effects, since 1-substituted lumazines and pterins give only 5-oxides and the presence of bulky substituents at position 7 also directs oxidation to N-5. The pteridine 5-oxide (52) and 8-oxide (53) and the 5,8-dioxide (55) contain the AT-oxide groups as such, even when the possibility of AT-hydroxy tautomers exists, as in (53) i(54). 

Various 6- and 7-methyl- and 6,7-dimethyl-pteridines bearing either oxo or amino groups in the 2- and 4-positions can be oxidized to the corresponding carboxylic acids by alkaline potassium permanganate on heating. Various lumazine and pterin mono- and di-carboxylic acids have been prepared in this way (48JA3026, 78CB3790). 

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. 

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. 

Another factor that characterizes molybdenum and tungsten enzymes is that instead of using the metal itself, directly coordinated to amino acid side-chains of the protein, an unusual pterin cofactor, Moco, is involved in both molybdenum- and tungsten-containing enzymes. The cofactor (pyranopterin-dithiolate) coordinates the metal ion via a dithiolate side-chain (Figure 17.2). In eukaryotes, the pterin side-chain has a terminal phosphate group, whereas in prokaryotes, the cofactor (R in Figure 17.2) is often a dinucleotide. 

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