Disease relevance of Pterin

• In order to further assess the role of xanthine oxidase in ischemia-reperfusion injury, we examined the influence of another inhibitor of the enzyme (pterin aldehyde) on the increased vascular permeability produced by intestinal ischemia [1].
• Similar results were obtained with pterin-free NOS-I expressed in Escherichia coli [2].
• Crystal structure of Mycobacterium tuberculosis 7,8-dihydropteroate synthase in complex with pterin monophosphate: new insight into the enzymatic mechanism and sulfa-drug action [3].
• Steady-state kinetic analysis of pterin-dependent phenylalanine hydroxylase from Chromobacterium violaceum indicated that the enzyme follows a partially ordered reaction mechanism [4].
• Stability of the heme environment of the nitric oxide synthase from Staphylococcus aureus in the absence of pterin cofactor [5].

Psychiatry related information on Pterin

• Abnormalities in urinary pterin levels in Rett syndrome [6].

High impact information on Pterin

• They absorb light and transmit the electromagnetic signal to the molecular clock using a pterin and flavin adenine dinucleotide (FAD) as chromophore/cofactors, and are evolutionarily conserved and structurally related to the DNA repair enzyme photolyase [7].
• Crystal structure of constitutive endothelial nitric oxide synthase: a paradigm for pterin function involving a novel metal center [8].
• Pterin binding refolds the central interface region, recruits new structural elements, creates a 30 angstrom deep active-center channel, and causes a 35 degrees helical tilt to expose a heme edge and the adjacent residue tryptophan-366 for likely reductase domain interactions and caveolin inhibition [9].
• In ischemic ileal segments pretreated with purified pterin aldehyde, vascular permeability increased to only 0.15 +/- 0.02 [1].
• Letter: Pterin administration as a therapy for P.K.U. due to dihydropteridine-reductase deficiency [10]?

Chemical compound and disease context of Pterin

• The pterin component of the molybdenum cofactor, termed molybdopterin, is synthesized in Escherichia coli by enzymes encoded at the chl loci [11].
• DNA photolyase from Escherichia coli contains both flavin and pterin [12].
• Resonance Raman spectra are compared for Rhodobacter sphaeroides dimethyl sulfoxide reductase, an enzyme containing a molybdopterin cofactor, and two model compounds, I and II, which have pterin and quinoxaline, respectively, attached to a Cp2Mo[IV]-dithiolene chelate [Cp = cyclopentadienyl] [13].
• Cyanide oxygenase (CNO) from Pseudomonas fluorescens NCIMB 11764 catalyzes the pterin-dependent oxygenolytic cleavage of cyanide (CN) to formic acid and ammonia [14].
• According to recent crystallographic studies, residue Tyr179 in Chromobacterium violaceum phenylalanine hydroxylase is located in the active site and its hydroxyl oxygen is 5.1 A from the iron, where it has been suggested to play a role in positioning the pterin cofactor [15].

Biological context of Pterin

• The latter consists of an N-terminal autoregulatory sequence (containing Ser 16, which is the site of phosphorylation) that extends over the active site pocket, and an alpha-beta sandwich core that is, unexpectedly, structurally related to both pterin dehydratase and the regulatory domains of metabolic enzymes [16].
• Because hydroxylation of tyrosine to dopa and of tryptophan to 5-hydroxytryptophan may require the same cofactor and pterin reductase as phenylalanine hydroxylase, these mutants may also prove useful for the study of the role of catecholamines and serotonin, substances known to be present in Tetrahymena [17].
• Pteridine reductase mechanism correlates pterin metabolism with drug resistance in trypanosomatid parasites [18].
• Among 13 major intermediates of pterin metabolism and two lumazines, xanthopterin (but not dihydroxanthopterin) was found to inhibit cell proliferation (half-maximum inhibition at 1.8 X 10(-5) M) during concanavalin A-induced lymphocyte activation in pre-stimulated lymphocytes and in a lymphoid cell line grown in continuous culture (LS-2) [19].
• Phosphorylation causes only a small additional reduction in the apparent Km for reduced pterin in striatal extracts from which catecholamines have been removed [20].

Anatomical context of Pterin

• The molybdenum cofactor biosynthetic protein Cnx1 complements molybdate-repairable mutants, transfers molybdenum to the metal binding pterin, and is associated with the cytoskeleton [21].
• The absence of hyperphenylalaninemia and the presence of normal urinary pterin metabolites and of normal SR-like activity in red blood cells may be explained by alternative pathways for the final two-step reaction of BH(4) biosynthesis in peripheral and neuronal tissues [22].
• In this article, we report two patients with progressive psychomotor retardation, dystonia, severe dopamine and serotonin deficiencies (low levels of 5-hydroxyindoleacetic and homovanillic acids), and abnormal pterin pattern (high levels of biopterin and dihydrobiopterin) in cerebrospinal fluid [22].
• Hybridoma cell lines isolated from the immunized mice secreted monoclonal antibodies reacting specifically with the pterin molecule and monoclonal antibodies which were found to bind phenylalanine hydroxylase [23].
• We have recently shown that interferon-gamma is capable of activating the key enzyme of pterin biosynthesis in macrophages [24].

Associations of Pterin with other chemical compounds

• Pretreatment with commercially prepared folic acid, which is contaminated with pterin aldehyde, also attenuated the ischemia-induced increase in vascular permeability (0.16 +/- 0.04) [1].
• Depletion of intracellular tetrahydrobiopterin with an inhibitor of de novo pterin synthesis resulted in a predominance of monomeric iNOS without a greater relative distribution of iNOS to the peroxisomal pool [25].
• The inhibition of DNA synthesis is reversed by repletion of cellular BH4 levels with sepiapterin, a pterin that is readily taken up by the cells and converted to BH4 by the sequential reductions of sepiapterin reductase and dihydrofolate reductase [26].
• When supplemented in vitro with pterin cofactors required for TH activity, these cells produced L-dopa and released it into the cell culture medium [27].
• Dihydropteridine reductase (DHPR; EC 1.6.99.7) catalyzes the NADH-mediated reduction of quinonoid dihydrobiopterin and is an essential component of the pterin-dependent aromatic amino acid hydroxylating systems [28].

Gene context of Pterin

• Collectively, these findings suggest (i) that, unlike the antifolate principle, the 4-amino substituent is not essential for developing pterin-based NOS inhibitors and (ii), provide a steric and electrostatic basis for their rational design [29].
• Characterization of a novel pterin intermediate formed in the catalytic cycle of tyrosine hydroxylase [30].
• The bound conformers of the substrate and the pterin were then docked into the modeled three-dimensional structure of TPH [31].
• The substitution of ornithine apparently does not perturb the pterin specificity of FPGS [32].
• Kinetic analysis of TH activity versus low concentrations of the pterin co-factor (0.05-0.4 mM) indicated that the stimulations elicited by CRF, SVG and UT were associated with an increase in the Vmax of the enzyme form with high affinity for the co-factor [33].

Analytical, diagnostic and therapeutic context of Pterin

• Equilibrium titration of HPPK into HMDP and AMPCPP showed an enhancement of fluorescence from the pterin ring of the substrate, and a dissociation constant of 36 nm was deduced for HMDP binding to the HPPK.AMPCPP binary complex [34].
• In this work we studied the spectroscopic and electrochemical properties of 4-HBCR by EPR and Mössbauer spectroscopy and identified the pterin cofactor as molybdopterin mononucleotide [35].
• HPLC product analysis showed that 7,8-BH(2) and pterin are the stable products generated from the reaction [36].
• Reference values of all enzyme activities and pterin production were measured in fibroblasts and also in amniocytes for prenatal diagnosis [37].
• Possible catalytic roles for these histidines in the hydroxylation mechanism of pterin-dependent monooxygenases are discussed along with potential future applications of the combination of ESEEM with site-directed mutagenesis [38].

References