Disease relevance of Formycin

• Adenosine-5'-monophosphate nucleosidase from Escherichia coli has been crystallized in the presence of its strong competitive inhibitor formycin 5'-monophosphate and its allosteric activator adenosine 5'-triphosphate [1].
• Formycin B is cytotoxic toward Leishmania and is a potential chemotherapeutic agent for leishmaniasis [2].
• The in vivo use of formycin B may be limited by its toxicity to humans due to the slight similar metabolism of the drug in human cells [3].
• Difluoromethylornithine and formycin B in toxoplasmosis [4].
• Inhibition of Rous sarcoma virus production by formycin [5].

High impact information on Formycin

• Uninfected macrophages also convert formycin B into the same products, but the levels are markedly lower than those seen in infected macrophages [6].
• Na(+)-dependent formycin B transport activity in intestinal epithelium decreases from jejunum to ileum and is absent in descending colon [7].
• From the metabolic profile, we conclude that formycin B is first converted to the 5'-monophosphate by the nucleoside phosphotransferase found in Leishmania and is subsequently converted to cytotoxic adenosine nucleotide analogs of formycin A that become incorporated into RNA [8].
• The nucleoside triphosphates (NTPs) with an amino group at the 6 position and hydrogen at the 8 position, and formycin 5'-triphosphate (FTP) were hydrolyzed by myosin very slowly in the presence of Mg2+ and rapidly in the presence of EDTA and K+ [9].
• In cell hybrids formed between FomR X FomS cells and FomR X Toyr cells, the formycin-resistant phenotype of both of the FomR mutants behaved codominantly [10].

Chemical compound and disease context of Formycin

• Crystal structure of the ternary complex of E. coli purine nucleoside phosphorylase with formycin B, a structural analogue of the substrate inosine, and phosphate (Sulphate) at 2.1 A resolution [11].
• We have examined the fluorescence decay, in neutral aqueous medium, of tyrosine (L-tyrosine and N-acetyl-L-tyrosinamide), and of the tyrosine residues in a tryptophan-free protein, the enzyme purine nucleoside phosphorylase from Escherichia coli in a complex with formycin A (an inhibitor), and orthophosphate (a co-substrate) [12].
• The effect of formycin, an adenosine analog, on the growth of chick embryo fibroblasts and on Rous sarcoma virus (RSV) production was studied [5].
• The proposed decay function was used to study effect of the interaction of E. coli purine nucleoside phosphorylase (PNP-I, the product of the deoD gene) with its specific inhibitor, viz. formycin A (FA), on fluorescence decays of ligand and enzyme tyrosine residues, in the presence of orthophosphate (P(i), a natural co-substrate) [13].
• Isocoformycin potentiated antitumor activity of formycin A and ara-A against L1210 leukemia [14].

Biological context of Formycin

• Formycin B inhibited growth of L5178Y mouse leukemia cells in concentrations of less than twice the concentration that inhibits cell proliferation at 50% by cytostasis; at higher concentrations (more than twice the 50% concentration mentioned), the cells were killed [15].
• In contrast, [3H]adenosine phosphorylation was insensitive to formycin A except at very high concentrations [16].
• Deletion of amino acids 128-135, corresponding to DGSELTLD, produced an enzyme with a 20-fold decrease in Vmax but with smaller changes in substrate saturation kinetics, activation by MgATP, inhibition by inorganic phosphate, and inhibition by the tight-binding inhibitor, formycin 5-phosphate [17].
• Study of the nucleotide binding site of the yeast Schizosaccharomyces pombe plasma membrane H+-ATPase using formycin triphosphate-terbium complex [18].
• Biochemical genetic analysis of formycin B action in Leishmania donovani [2].

Anatomical context of Formycin

• These data indicate that there are two sodium-dependent mechanisms for nucleoside transport in mouse intestinal epithelial cells, and that formycin B and thymidine may serve as model substrates to distinguish between these transporters [19].
• Purine nucleoside phosphorylase (EC 2.4.2.1) has been purified 715-fold from human granulocytes by formycin B affinity chromatography [20].
• Antileishmanial activity of human red blood cells containing formycin A [3].
• A number of the new enzymatically synthesized 2',5'-oligonucleotide trimers, namely, those containing the nucleosides 8-azaadenosine, toyocamycin, sangivamycin, formycin, 8-bromoadenosine, tubercidin, and guanosine, were found to inhibit protein synthesis and cellular proliferation after uptake into intact L and HeLa cells [21].
• Dual effect of formycin A upon the hydrolysis of phosphoinositides in perifused pancreatic islets [22].

Associations of Formycin with other chemical compounds

• The formycin B inhibitory effect on cell proliferation was reduced by coincubation with nicotinamide adenine diphosphate or adenosine [15].
• Influence of formycin B on polyadenosine diphosphoribose synthesis in vitro and in vivo [15].
• It was concluded that a hydrogen bond between the hydroxyl of serine-123 and the C4 amino group of cytidine or the C-7 amino group of formycin is not important for substrate binding and catalytic activity [23].
• The catalytic site of AMP nucleosidase. Substrate specificity and pH effects with AMP and formycin 5'-PO4 [24].
• Carbon-13 magnetic resonance spectra of C-nucleosides. 3. la-c Tautomerism in formycin and formycin B and certain pyrazolo[4,3-d]pyrimidines [25].

Gene context of Formycin

• The ternary complex of purine nucleoside phosphorylase from E. coli with formycin B and a sulphate or phosphate ion crystallized in the hexagonal space group P6122 with unit cell dimensions a=123.11, c=241.22 A and three monomers per asymmetric unit [11].
• The TUBA2 clone was also 1000-fold less sensitive than the parental line to growth inhibition by formycin A, another cytotoxic adenosine analog [26].
• Formycin B, purine nucleoside phosphorylase and lymphocyte function [27].
• The possibility that formycin B was inhibiting adenosine deaminase, for which it is a product analogue, was studied by the analysis of reaction progress curves using the integrated rate equation [27].
• Formycin anhydronucleosides. Conformation of formycin and conformational specificity of adenosine deaminase [28].

Analytical, diagnostic and therapeutic context of Formycin

• The purification involves DEAE-Sephadex chromatography followed by affinity chromatography on a column of Sepharose/formycin B [29].
• Several 3-beta-D-ribofuranosyl-1,2,4-triazolo[3,4-f]-1,2,4-triazines related to formycin were prepared and tested for their antitumor activity in cell culture [30].
• The advantages of using HPLC to examine the interconnecting activities of a multienzyme complex in subcellular fractions are discussed, including the increased sensitivity obtained by using formycin analogs in the assay procedures.(ABSTRACT TRUNCATED AT 400 WORDS)[31]
• The levels of formycin B in serum after the final oral administration of 26 mg/kg/day were 1.4 micrograms/ml at 1 hr and 0.3 microgram/ml at 2 hr [32].
• This early inhibitory effect of formycin A upon insulin release coincided, in perforated patch whole-cell recordings, with an initial transient increase of ATP-sensitive K+ channel activity [33].

References