Disease relevance of AMP-PCP

• We have determined the crystal structure of PRK from Rhodobacter sphaeroides bound to the ATP analogue AMP-PCP to a resolution of 2.6 A [1].
• The mechanism underlying beta,gamma-methylene ATP (beta,gamma-MeATP)-induced cAMP elevation was investigated in rat glioma C6Bu-1 cells [2].
• Selective biopanning assays were done and phages were eluted using ATP, a non-hydrolysable ATP analogue and the protein FtsZ known to interact with FtsA in the divisome during the process of bacterial cell division [3].
• The glycerol-inactivated holoenzyme in permeabilized cells (in situ) of E. coli harboring a plasmid containing the diol dehydratase genes and their flanking regions was rapidly reactivated in the presence of free AdoCbl, ATP, and Mg2+. beta,gamma-Methylene ATP was not able to replace ATP [4].
• 5. alpha,beta-methylene-ATP inhibited ileal muscle ACh induced contractures while it potentiated both phasic and tonic K-induced contractures. beta,gamma-methylene ATP inhibited ACh-induced contractures but it enhanced K-induced phasic contractures while inhibiting K-induced tonic force [5].

High impact information on AMP-PCP

• ATP analogs substituted in the gamma-phosphorus (ATPgammaS, beta, gamma-imido-ATP, and beta,gamma-methylene-ATP) were used to probe the involvement of P2 receptors in the modulation of synaptic transmission in the hippocampus, because their extracellular catabolism was virtually not detected in CA1 slices [6].
• We studied by mutational analysis the protective effect of AMP-PCP, an ATP analog that is not utilized for enzyme phosphorylation [7].
• On the other hand, alpha,beta-methylene-ATP, beta,gamma-methylene-ATP, and UTP were unable to induce any rise in [Ca2+]i. This pharmacological profile is consistent with expression of P2X2 and/or P2X5 purinergic receptor channels [8].
• The nonhydrolyzable ATP analog, beta,gamma-methylene-ATP, did not support peptide hydrolysis [9].
• Since the nonhydrolyzable ATP analog AMP-PCP is also active and since addition of kinases A and C as well as alkaline phosphatase does not modify the ATP effect, it is concluded that ATP hydrolysis is not required [10].

Biological context of AMP-PCP

• Equilibrium binding was activated by Ca2+ (KD/Ca2+ = 14 nM), inhibited by Mg2+ (IC50 = 5.0 mM), and unaffected by AMP-PCP or caffeine [11].
• 5. (i) Omission of ATP from the pipette solution, (ii) ATP replacement by the non-hydrolysable ATP analogue 5'-adenylylimidodiphosphate, and (iii) inhibition of protein kinase C by staurosporine or calphostin C accelerated the activation kinetics of the current and increased its amplitude, but did not alter its pharmacological properties [12].
• The rank-order potency for vasoconstriction caused by several ATP analogs was alpha,beta-methylene ATP (alpha,beta-MeATP) > beta,gamma-methylene ATP = 2-methylthioATP > ATP > ADP [13].
• Competitive binding experiments, based on the ability of nucleotides and ATP analogs to block [35S]ATP gamma S binding to PMN, revealed a rank order of ATP gamma S greater than ATP greater than 2-MeS-ATP = 8-Bromo ATP greater than ADP = ITP greater than AMP-PCP = GTP much greater than CTP [14].
• They respond to the agonist beta,gamma-methylene ATP with a transient depolarizing receptor potential, Ca(2+)-based action potentials and repetitive bouts of forward and backward swimming called 'avoiding reactions' (AR) [15].

Anatomical context of AMP-PCP

• We propose that the Cl- channel or a regulator of the channel, that is activated by the non-hydrolyzable ATP analog AMP-PCP in ZG membranes, is a member of the ATP binding cassette superfamily of transporters and may have homology to MDR1 P-glycoprotein [16].
• The regulation of Cl- and cation conductances by the nonhydrolyzable ATP analog adenosine 5'-(beta,gamma-methylene)triphosphate (AMP-PCP) was characterized in isolated zymogen granules (ZG) from pancreatic acinar cells [16].
• Isolated sarcotubular membranes (SR) from skeletal muscle bound 3.7 nmol of beta, gamma-methylene [8-3H]ATP (AMP-PCP) per mg of membrane protein [17].
• In the presence of AMP-PCP (beta, gamma-methyleneadenosine 5'-triphosphate), a non-hydrolyzable analog of ATP, negative stain images of increased morphological detail indicate that the dynein arm, attached to ciliary doublet microtubules, is composed of subunits including a cape, an elongated body and a head [18].
• [3H]Ryanodine binding to skeletal and cardiac muscle membranes was enhanced by addition of oxidized AP4A Ap5A, and AMP-PCP [19].

Associations of AMP-PCP with other chemical compounds

• The possibility that the extracellular ATP activation of Cl- currents in CFTR-expressing C127i cells was mediated by a P2-type purinergic receptor was supported by studies in which the effect of external ATP on the Cl- currents was mimicked by the ATP analogs, ATP gamma S and beta,gamma-methylene ATP, but not the uridine nucleotide, UTP [20].
• Hydrolysis of a nucleoside triphosphate is required rather than mere NTP binding as deduced from a comparison of unwinding in the presence of ATP and AMP-PCP [21].
• Limited supercoiling can be achieved in the presence of the non-hydrolysable ATP analogue, 5'-adenylyl beta,gamma-imidodiphosphate (ADPNP) [22].
• The effect of P-ATP on the stability of open states was more evident when ATP hydrolysis was abolished, either by mutating the nucleotide-binding domain 2 (NBD2) Walker B glutamate (i.e. E1371) or by using the non-hydrolysable ATP analogue AMP-PNP [23].
• Binding of AMP-PCP produced larger fluorescence changes, comparable to those observed on phosphorylation with ATP or acetyl phosphate [24].

Gene context of AMP-PCP

• A brief application of ATP and beta,gamma-methylene ATP (beta,gamma-MeATP) also induced the CFTR current in a manner similar to that seen with Ade [25].
• The ATP analog, adenylyl methylenediphosphonate (AMP-PCP), and two triarylimidazoles were competitive inhibitors versus ATP and uncompetitive inhibitors versus GST-ATF2 [26].
• [(3)H]ryanodine binding data also showed that Mg(2+)-dependent inhibition of RyR1-slow was reduced in the presence of AMP-PCP [27].
• Membranes prepared from these cells displayed a single affinity state for CCK but two affinity states could be restored in the presence of GTP[gamma S], ATP and ATP[gamma S] but not AMP-PCP [28].
• Adenosine, alpha,beta-methylene- ATP and beta,gamma-methylene-ATP were ineffective in stimulating mucin release [29].

Analytical, diagnostic and therapeutic context of AMP-PCP

• Electron microscopy revealed that FliI assembles to a ring structure, the yield of which was increased by the presence of a non-hydrolysable ATP analogue [30].
• The sigma receptor ligands pentazocine and SKF10047 modulated K+ channels, despite intra-terminal perfusion with GTP-free solutions, a G-protein inhibitor (GDPbetaS), a G-protein activator (GTPgammaS) or a non-hydrolysable ATP analogue (AMPPcP) [31].
• The ectoATPase activity, measured by HPLC technique was not significantly different at 37 degrees C and 12 degrees C. Nifedipine (1 microM), the voltage sensitive Ca2+ channel blocker eliminated beta,gamma-methylene-ATP evoked twitch contraction but not ATP release [32].
• ADP and beta,gamma-methylene-ATP had little or no effect on [Ca2+]i. Finally, RT-PCR produced a 330-bp fragment from LLC-PK1 cell RNA, whose sequence was 80% identical to the rat P2X1 receptor [33].

References