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Dihydroneopterin

In E. coli GTP cyclohydrolase catalyzes the conversion of GTP (33) into 7,8-dihydroneoptetin triphosphate (34) via a three-step sequence. Hydrolysis of the triphosphate group of (34) is achieved by a nonspecific pyrophosphatase to afford dihydroneopterin (35) (65). The free alcohol (36) is obtained by the removal of residual phosphate by an unknown phosphomonoesterase. The dihydroneoptetin undergoes a retro-aldol reaction with the elimination of a hydroxy acetaldehyde moiety. Addition of a pyrophosphate group affords hydroxymethyl-7,8-dihydroptetin pyrophosphate (37). Dihydropteroate synthase catalyzes the condensation of hydroxymethyl-7,8-dihydropteroate pyrophosphate with PABA to furnish 7,8-dihydropteroate (38). Finally, L-glutamic acid is condensed with 7,8-dihydropteroate in the presence of dihydrofolate synthetase. [Pg.41]

Goyer, A. et al.. Folate biosynthesis in higher plants. cDNA cloning heterologous expression and characterization of dihydroneopterin aldolases, Plant. Physiol, 135, 103, 2004. [Pg.120]

Gieseg, S.P., Maghzal, G., and Glubb, D., Protection of erythrocytes by the macrophage synthesized antioxidant 7,8 dihydroneopterin. Free Radic. Res., 34, 123, 2001. Gieseg, S.P. and Cato, S., Inhibition of THP-1 cell-mediated low-density lipoprotein oxidation by the macrophage-synthesised pterin, 7,8-dihydroneopterin, Redox Rep., 8, 113, 2003. [Pg.121]

Baird, S.K. et al., OxLDL induced cell death is inhibited by the macrophage synthesised pterin, 7,8-dihydroneopterin, in U937 cells but not THP-1 cells, Biochim. Biophys. Acta 1745, 361, 2005. [Pg.121]

Determination of GTP cyclohydrolase and D-erythro-7,8-dihydroneopterin triphosphate synthetase... [Pg.229]

FIGURE 40-2 The phenylalanine hydroxylase (PAH) pathway. Phenylketonuria usually is caused by a congenital deficiency of PAH (reaction 1), but it also can result from defects in the metabolism of biopterin, which is a cofactor for the hydroxylase. Enzymes (1) Phenylalanine hydroxylase (2) Dihydropteridine reductase (3) GTP cyclohydrolase (4) 6-pyruvoyltetrahydrobiopterin synthase. BH4, tetrahydrobiopterin DEDT, o-erythro-dihydroneopterin triphosphate QH2, dihydrobiopterin. [Pg.672]

Dihydroneopterin aldolase (Table 1, entry 8) Inhibitors (such as 33) of dihydro-neopterin aldolase were identified using high throughput X-ray-based fragment screening of a 10,000 member random library [43]. Structure-guided optimisation gave potent leads such as 35. [Pg.442]

Figure 10.1 shows a two-dimensional [15N, H]-TROSY correlation spectrum of the 15N,2H- labeled 110 kDa homo-octameric protein 7,8-dihydroneopterin aldolase from Staphylococcus aureus (DHNA) measured with the pulse sequence of Fig. 10.4 [13]. The gain in spectral resolution and sensitivity is readily apparent from comparison with the corresponding conventional experiment. The optimal sensitivity is achieved by adjusting the polarization transfer r in Fig. 10.4 (3 ms <2r<5.4 ms [3]). For an optimal suppression of the non-TROSY components, the so-called Clean TROSY might be used [19]. Similar signal and spectral resolution enhancements are achieved for 15N,2H-labeled or 13C,15N,2H-... Figure 10.1 shows a two-dimensional [15N, H]-TROSY correlation spectrum of the 15N,2H- labeled 110 kDa homo-octameric protein 7,8-dihydroneopterin aldolase from Staphylococcus aureus (DHNA) measured with the pulse sequence of Fig. 10.4 [13]. The gain in spectral resolution and sensitivity is readily apparent from comparison with the corresponding conventional experiment. The optimal sensitivity is achieved by adjusting the polarization transfer r in Fig. 10.4 (3 ms <2r<5.4 ms [3]). For an optimal suppression of the non-TROSY components, the so-called Clean TROSY might be used [19]. Similar signal and spectral resolution enhancements are achieved for 15N,2H-labeled or 13C,15N,2H-...
DIHYDROLIPOAMIDE DEHYDROGENASE DIHYDRONEOPTERIN ALDOLA.SE DIHYDRONEOPTERIN TRIPHOSPHATE... [Pg.737]

Folate biosynthesis has also been studied in plants and the dihydroneopterin aldolase from Arabidopsis thaliana has been crystallized and its structure determined the construction of the active site has similarities with those of other... [Pg.958]

The stereochemical course of the reaction catalyzed by dihydroneopterin aldolase has been established <2002JBC28841>. By carrying out the reaction in deuterium oxide and using multinuclear NMR spectroscopy of folate derived from the reaction product, 6-hydroxymethylpterin, it was shown that the late-stage enol intermediate undergoes protonation to form 6-hydroxymethylpterin with deuterium predominantly in the A-configuration. [Pg.961]

The putative E. coli gene of the 6-pyruvoyltetrahydropterin synthase (PTPS) was cloned and overexpressed in order to identify the enzymatic activity to synthesize 6-pyruvoyltetrahydropterin from dihydroneopterin triphosphate <2002MI234>. The protein was shown to have another new catalytic function to convert sepiapterin to 7,8-dihydroneopterin. [Pg.966]

The structure of dihydroneopterin aldolase has been analyzed further with respect to the functional roles of conserved active site glutamate and lysine residues <2006B15232>. NMR studies have also suggested that the isomerization of dihydroneopterin to dihydromonapterin catalyzed by the same enzyme involves the action of the same functional groups <2007MI2240>. [Pg.968]

GTPCH (EC 3.5.4.16) converts the substrate GTP to 7,8-dihydroneopterin triphosphate (H2NTP) and formate. GTPCH activity is determined by measuring neopterin, the completely oxidized and dephosphorylated H TP-product of the enzyme reaction. Conversion of H2NTP to neopterin is carried out after the enzymatic reaction in presence of iodine at pH 1.0, followed by dephosphorylation with alkaline phosphatase at pH 8.5-9.0. Neopterin is detected fluorimetrically at 350/440 nm upon HPLC separation. The assay is based with some modifications on the methods published by Viveros et al. and Hatakeyama and Yoneyama [15,16]. [Pg.686]

PTPS (EC 4.6.1.10) converts the substrate 7,8-dihydroneopterin triphosphate (H2NTP) in a manganese-dependent reaction to the highly unstable intermediate... [Pg.689]

Severin, J. M., Walter, K., Magdalinos, P., Jakob, C. G., Wagner, R., and Beutel, B. A. (2004). Discovery of potent inhibitors of dihydroneopterin aldolase using CrystaLEAD high-throughput X-ray crystallographic screening and structure-directed lead optimization. Journal of Medicinal Chemistry 47, 1709-1718. [Pg.33]

GCH catalyses the hydrolytic release of formate from GTP (135) followed by cyclization to dihydroneopterin triphosphate (136) [139]. GCH is the rate-limiting enzyme for the biosynthesis of BH4 (43), and the cellular BH4 content is regulated mainly by the activity of this enzyme. [Pg.162]

Studies of reaction mechanisms and enzymic reactions rely to a great extent on labeled adducts. The anticipated synthesis of the labeled precursors often are achieved only by multistep procedures performed chemically or enzymatically. Isotope-labeled dihydroneopterin 3 -triphosphate (51), with 3H at positions C-T and C-2, respectively, has been prepared from isotope-labeled glucose as starting material. [Pg.691]

The enzymatic interconversion of 7,8-dihydroneopterin-5 -triphosphate into tetrahydrobiopterin consists of a series of reactions of which each step has now been unraveled and characterized. In the de novo biosynthesis of tetrahydrobiopterin it was noticed that the C(6)-H is derived from H20 whereas NADPH is used in the conversion from sepiapterin <85JBC(260)522l>. [Pg.724]

The first chemical synthesis of 7,8-dihydroneopterin-3 -triphosphate (477), the biosynthetic precursor of all naturally occurring pterin derivatives, has been achieved from neopterin-3 -monophos-phate (474) by formylation of the two hydroxy groups (475) followed by coupling with pyrophosphate to (476). Chemical or catalytic reduction resulted in the 7,8-dihydro derivative (477), which was fully active as a substrate in enzymic reactions <88BBR(152)1193>. [Pg.733]


See other pages where Dihydroneopterin is mentioned: [Pg.323]    [Pg.108]    [Pg.113]    [Pg.439]    [Pg.246]    [Pg.201]    [Pg.201]    [Pg.923]    [Pg.924]    [Pg.924]    [Pg.924]    [Pg.959]    [Pg.959]    [Pg.959]    [Pg.670]    [Pg.691]    [Pg.884]    [Pg.1460]    [Pg.1460]    [Pg.1461]    [Pg.323]    [Pg.282]    [Pg.248]    [Pg.262]    [Pg.722]    [Pg.724]    [Pg.210]   
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See also in sourсe #XX -- [ Pg.1460 ]

See also in sourсe #XX -- [ Pg.315 ]

See also in sourсe #XX -- [ Pg.7 , Pg.1248 ]




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Aldolases dihydroneopterin aldolase

Dihydroneopterin aldolase

Dihydroneopterin triphosphate

Erythro- 7,8- Dihydroneopterin triphosphate

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