4578-31-8Relevant articles and documents
Structural insights into the novel diadenosine 5′,5?-P 1,P4-tetraphosphate phosphorylase from Mycobacterium tuberculosis H37Rv
Mori, Shigetarou,Shibayama, Keigo,Wachino, Jun-Ichi,Arakawa, Yoshichika
, p. 93 - 104 (2011)
Rv2613c is a diadenosine 5′,5?-P1,P 4-tetraphosphate (Ap4A) phosphorylase from Mycobacterium tuberculosis H37Rv. Sequence analysis suggests that Rv2613c belongs to the histidine triad (HIT) motif superfamily, which includes HIT family diadenosine polyphosphate (ApnA) hydrolases and Ap4A phosphorylases. However, the amino acid sequence of Rv2613c is more similar to that of HIT family ApnA hydrolases than to that of typical Ap4A phosphorylases. Here, we report the crystal structure of Rv2613c, which is the first structure of a protein with ApnA phosphorylase activity, and characterized the structural basis of its catalytic activity. Our results showed that the structure of Rv2613c is similar to those of other HIT superfamily proteins. However, Asn139, Gly146, and Ser147 in the active site of Rv2613c replace the corresponding Gln, Gln, and Thr residues that are normally found in HIT family ApnA hydrolases. Furthermore, analyses of Rv2613c mutants revealed that Asn139, Gly146, and Ser147 are important active-site residues and that Asn139 has a critical role in catalysis. The position of Gly146 might influence the phosphorylase activity. In addition, the tetrameric structure of Rv2613c and the presence of Trp160 might be essential for the formation of the Ap4A binding site. These structural insights into Rv2613c may facilitate the development of novel structure-based inhibitors for treating tuberculosis.
Supported Synthesis of Adenosine Nucleotides and Derivatives on a Benzene-Centered Tripodal Soluble Support
Appy, Lucie,Peyrottes, Suzanne,Roy, Béatrice
, (2021/06/23)
The first soluble-phase synthesis of adenosine nucleotides including α,β and β,γ-methylene bisphosphonate analogues on a multi-pod support is reported. Anchoring of a 2’,3’-protected purine nucleoside to the tripodal support via the nucleobase was successfully achieved using a microwave assisted Cu(I)-catalyzed azide-alkyne cycloaddition. Then, phosphorylation was performed, followed by cleavage with aqueous ammonia to provide adenine derivatives, and finally deprotection. When using benzylamine instead of ammonia, a derivative with N6-benzylamine adenine as nucleobase was obtained. This methodology allows to access adenosine 5’-mono, di and triphosphates, as well as various analogues of pharmacological interest in modest to good yields.
Multiple molecular recognition and catalysis. A multifunctional anion receptor bearing an anion binding site, an intercalating group, and a catalytic site for nucleotide binding and hydrolysis
Hosseini, Mir Wais,Blacker, A. John,Lehn, Jean-Marie
, p. 3896 - 3904 (2007/10/02)
The multifunctional receptor molecule 2 has been designed and synthesized in order to achieve higher molecular recognition and reaction selectivity via multiple interactions with bound substrates. It combines three functional subunits: two recognition sites - a macrocyclic polyammonium moiety as anion binding site and an acridine side-chain for stacking interactions - as well as a catalytic amino group in the macrocycle for facilitating hydrolytic reactions. Compound 2 binds mono- and dinucleotide polyphosphates by simultaneous interactions between its macrocyclic polycationic moiety and the polyphosphate chain as demonstrated by 31P NMR spectroscopy and by stacking between its acridine derivative and the nucleic base of nucleotides as observed by both 1H NMR spectroscopy and by fluorescence spectrophotometry. Binding of nucleotides by protonated 2 induces significant upfield shifts of the polyphosphate signals and of protons of the acridine moiety of 2 as well as of the adenine and the anomeric proton of the nucleotides; at the same time the proton signals corresponding to CH2 groups of the macrocyclic part of 2 are downfield shifted. Upon complexation of ATP and CTP, the fluorescence emission of 2 is enhanced, whereas guanosine triphosphate causes a slight quenching; thus, 2 acts as a sensitive and selective fluorescent probe for ATP. At neutral pH the hydrolytic reaction proceeds, at least in part, through a covalent intermediate, the phosphorylated macrocycle 2 indicating nucleophilic catalysis. Compound 2 shows greater selectivity between ATP and ADP than the parent compound 1 which does not contain the acridine binding site. 2 also binds strongly to DNA plasmid pBR 322 at 10-6 M probably via a double type of interaction, involving both intercalation and electrostatic interactions with the phosphate groups.
