Disease relevance of Aminopyridine

• Selected pairs of protonated ribosomal proteins were reconstituted into deuterated 50S subunits from Escherichia coli ribosomes [1].
• Evidence that the cell wall of Bacillus subtilis is protonated during respiration [2].
• Based on these results we propose that this binding of protonated cytosines to the coat protein of turnip yellow mosaic virus may represent a new motif in RNA-protein interactions [3].
• Measurements were performed with photosystem I (PS-I) preparations, whole cells from cyanobacteria grown in 2H2O, and photosystem II (PS-II) preparations, as well as with protonated PS-I preparations [4].
• Since it is known that such mismatches can be protonated and protonated cytosines play an important role in RNA-protein interactions in tymoviral virions, the influence of pH on the conformation of the internal loop was studied [5].

High impact information on Aminopyridine

• A structure in which dA:dT Watson-Crick base pairs alternate with Hoogsteen syndG:dCH+ pairs appears to be the most stereochemically acceptable structure consistent with the chemical properties of this protonated DNA [6].
• A protonated form of a cloned simple repeating DNA sequence d(TC)n X d(GA) is detectable in equilibrium with the usual Watson-Crick base-paired form at pHs up to 7 [6].
• Its seven transmembrane helices encompass a proton translocation pathway containing the chromophore, a retinal molecule covalently bound to lysine 216 through a protonated Schiff base, and a series of proton donors and acceptors [7].
• The lifetime of the protonated state correlates with the occupancy of an intra-channel binding site by the permeant cation [8].
• Hydrogen ions gain access to this region of the sodium channel (and hence determine the relative local concentration of protonated drug) more readily from the extracellular fluid than from the axoplasm (Schwarz et al 1977) [9].

Chemical compound and disease context of Aminopyridine

• The reduction rate of Escherichia coli thioredoxin by dithiothreitol is directly proportional to the fraction of Asp-26 in the protonated form over the pH range of 6-9 [10].
• A mechanism proposed for lactose/H(+) symport by the lactose permease of Escherichia coli indicates that lactose permease is protonated prior to ligand binding [11].
• There are large changes in the phosphate backbone torsion angles (particularly gamma) of the purine strand, probably due to the electrostatic interactions between the phosphate groups and the protonated cytosine [12].
• On the basis of our calculations, we propose that in the HIV-1 PR-inhibitor complex only one catalytic aspartic acid residue is protonated and that the binding free energy of the S isomer is ca. 2.8 kcal/mol higher than that of the R isomer [13].
• Both cytosine and adenine residues of TYMV RNA are protonated in substantial numbers near pH 4.5, suggesting elevation of their respective pKa values within the virion [14].

Biological context of Aminopyridine

• Both the solution and the antibody-catalyzed hydrolysis of the ketal substrates are shown to be specific acid catalyzed, involving the unimolecular cleavage of the protonated substrate or antibody-substrate complex in the rate-determining step [15].
• Two-photon spectroscopy of locked-11-cis-rhodopsin: evidence for a protonated Schiff base in a neutral protein binding site [16].
• Thus, we find that the protein conformations of the M and N intermediates of the photocycle are essentially the same, in spite of the fact that in M the Schiff base is unprotonated and in N it is protonated [17].
• Although Dronpa exists in an acid-base equilibrium, only the photoinduced protonated form shows the switching behavior [18].
• Base pairing and mutagenesis: observation of a protonated base pair between 2-aminopurine and cytosine in an oligonucleotide by proton NMR [19].

Anatomical context of Aminopyridine

• This S163R mutation provides insight into a mechanism by which PfCRT could gate the transport of protonated chloroquine through the digestive vacuole membrane [20].
• Previous in vitro experiments suggest that protonated 2,4,6-triaminopyrimidine (TAP+) inhibits passive Na+ movement across tight junctions of various epithelial tissues [21].
• CONCLUSIONS: Uptake of glycine- or taurine-conjugated bile acids by the guinea pig jejunum occurs by at least two mechanisms: carrier-mediated transport (dihydroxy conjugates greater than trihydroxy conjugates) and passive absorption in protonated (uncharged) form of glycine conjugates [22].
• With few exceptions, weakly basic compounds that are sufficiently lipophilic in their neutral forms and sufficiently hydrophilic in their protonated forms accumulate in lysosomes [23].
• Fourier difference maps were calculated from the differences in inplane diffraction from the deuterated membranes and from protonated samples that were prepared in exactly the same way [24].

Associations of Aminopyridine with other chemical compounds

• Here we report that binding of permeant cations to an intra-channel binding site of the dihydropyridine (DHP)-sensitive (L-type) Ca2+ channel leads to a conformational change which destabilizes the protonated state of a group on the external channel surface, and can shift its apparent pK value by more than 2 pH units [8].
• Rhodopsin is composed of two parts: a polypeptide chain called opsin and an 11-cis-retinal chromophore covalently bound to the protein by means of a protonated Schiff base linkage to Lys296 located in the seventh transmembrane segment of the protein [25].
• When intraluminal pH was decreased to pH 5.0, the absorption rate of glycine (but not taurine) conjugates increased, indicating passive absorption of the protonated species of glycine-conjugated bile acids [22].
• In native apomyoglobin, His-24 cannot be protonated, although at pH 4 the native protein forms a molten globule folding intermediate in which the histidine residues are readily protonated [26].
• In contrast, the pairing of protonated cytosine is consistent with the greater stability of oligonucleotide duplexes containing cytosine.O6-MeGua as compared with thymine.O6-MeGua base pairs [Gaffney, B. L., Markey, L. A. & Jones, R. A. (1984) Biochemistry 23, 5686-5691] [27].

Gene context of Aminopyridine

• Rhodopsin bears 11-cis-retinal covalently bound by a protonated Schiff base linkage [28].
• We have hypothesized that the anionic fatty acid head group is translocated by UCP, and the proton is transported electroneutrally in the bilayer by flip-flop of the protonated fatty acid [29].
• We conclude that the binding site of Drosophila rhodopsin is similar to that of bovine rhodopsin and is characterized by a protonated Schiff base chromophore stabilized via a single negatively charged counterion [30].
• Together, these results suggest that histidine 295 is not protonated in EAAC1 at physiological pH and, thus, does not contribute to H(+) cotransport [31].
• We found that the compounds with a nitro group on the benzyl ring were poor substrates for P-gp despite the presence of a secondary amine that can be protonated [32].

Analytical, diagnostic and therapeutic context of Aminopyridine

• Analysis of the theoretical microscopic titration curves for all of the ionizable residues of these proteins shows that a small fraction (3-7%) of the curves possess a flat region where the residue is partially protonated over a wide pH range [33].
• FTIR difference spectral changes in the bR570-to-K transition clearly indicate that bR570 contains a protonated Schiff base [34].
• Resonance Raman spectroscopy provides evidence that bR570 is protonated, but these results have been questioned on the basis of theoretical and experimental grounds [34].
• It is fully confirmed that the colorless light-activated intermediate recorded by millisecond time-resolved crystallography [Genick, U. K., Borgstahl, G. E. O., Ng, K., Ren, Z., Pradervand, C., et al. (1997) Science 275, 1471-1475] is protonated, nicely matching the spectroscopic features of the photoproduct PYP(M) [35].
• FAB-MS analysis of the HPLC fractions gave numerous protonated molecular ions ranging from m/z 491 to 2662 [36].

References