Pterins proteins

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... 

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. 

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. 

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. 

Fig. 6. The active site architecture of eNOS in the A subunit. L-Arg is held in place by several H-bonds with conserved groups. The H4B is sandwiched between aromatic groups contributed from each subunit Trp449 in subunit A and Phe462 in subunit B. Note that the amino group of L-Arg and the pterin donate an H-bond to the same heme propionate, which helps to understand the observed interdependence of pterin and substrate binding. The schematic diagram illustrates the extensive contacts between pterin and protein groups in each subunit.

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... 

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). 

The hereditary absence of phenylalanine hydroxylase, which is found principally in the liver, is the cause of the biochemical defect phenylketonuria (Chapter 25, Section B).430 4308 Especially important in the metabolism of the brain are tyrosine hydroxylase, which converts tyrosine to 3,4-dihydroxyphenylalanine, the rate-limiting step in biosynthesis of the catecholamines (Chapter 25), and tryptophan hydroxylase, which catalyzes formation of 5-hydroxytryptophan, the first step in synthesis of the neurotransmitter 5-hydroxytryptamine (Chapter 25). All three of the pterin-dependent hydroxylases are under complex regulatory control.431 432 For example, tyrosine hydroxylase is acted on by at least four kinases with phosphorylation occurring at several sites.431 433 4338 The kinases are responsive to nerve growth factor and epidermal growth factor,434 cAMP,435 Ca2+ + calmodulin, and Ca2+ + phospholipid (protein kinase C).436 The hydroxylase is inhibited by its endproducts, the catecholamines,435 and its activity is also affected by the availability of tetrahydrobiopterin.436... 

Aromatic compounds arise in several ways. The major mute utilized by autotrophic organisms for synthesis of the aromatic amino acids, quinones, and tocopherols is the shikimate pathway. As outlined here, it starts with the glycolysis intermediate phosphoenolpyruvate (PEP) and erythrose 4-phosphate, a metabolite from the pentose phosphate pathway. Phenylalanine, tyrosine, and tryptophan are not only used for protein synthesis but are converted into a broad range of hormones, chromophores, alkaloids, and structural materials. In plants phenylalanine is deaminated to cinnamate which yields hundreds of secondary products. In another pathway ribose 5-phosphate is converted to pyrimidine and purine nucleotides and also to flavins, folates, molybdopterin, and many other pterin derivatives. 

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.

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