Home  About us  Contact
 

Diphosphate Derivatives (diphosphate + derivative)

Distribution by Scientific Domains
Chemistry100%

Selected Abstracts

Structure-Based Design, Synthesis, and Evaluation of 2,-(2-Hydroxyethyl)-2,-deoxyadenosine and the 5,-Diphosphate Derivative as Ribonucleotide Reductase Inhibitors

CHEMMEDCHEM, Issue 10 2009
Dianqing Sun Dr.
Abstract Analysis of the recently solved X-ray crystal structures of Saccharomyces cerevisiae ribonucleotide reductase,I (ScRnr1) in complex with effectors and substrates led to the discovery of a conserved water molecule located at the active site that interacted with the 2,-hydroxy group of the nucleoside ribose. In this study 2,-(2-hydroxyethyl)-2,-deoxyadenosine 1 and the 5,-diphosphate derivative 2 were designed and synthesized to see if the conserved water molecule could be displaced by a hydroxymethylene group, to generate novel RNR inhibitors as potential antitumor agents. Herein we report the synthesis of analogues 1 and 2, and the co-crystal structure of adenosine diphosphate analogue 2 bound to ScRnr1, which shows the conserved water molecule is displaced as hypothesized. [source]

Structure of an N-terminally truncated Nudix hydrolase DR2204 from Deinococcus radiodurans

ACTA CRYSTALLOGRAPHICA SECTION F (ELECTRONIC), Issue 11 2009
A. M. D. Gonçalves
Nudix pyrophosphatases are a well represented protein family in the Deinococcus radiodurans genome. These hydrolases, which are known to be enzymatically active towards nucleoside diphosphate derivatives, play a role in cleansing the cell pool of potentially deleterious damage products. Here, the structure of DR2204, the only ADP-ribose pyrophosphatase in the D. radiodurans genome that is known to be active towards flavin adenosine dinucleotide (FAD), is presented at 2.0,Å resolution. [source]

Overexpression, crystallization and preliminary X-ray crystallographic analysis of Nudix hydrolase Orf141 from Escherichia coli K-1

ACTA CRYSTALLOGRAPHICA SECTION F (ELECTRONIC), Issue 9 2007
Junho Jung
Nudix hydrolases are a family of proteins that contain the characteristic amino-acid sequence GX5EX7REUXEEXGU (where U is usually I, L or V), the Nudix signature sequence. They catalyze the hydrolysis of a variety of nucleoside diphosphate derivatives such as nucleoside triphosphates, nucleotide sugars, ADP-ribose, dinucleotide coenzymes, diadenosine oligophosphates and capped RNAs. Recently, three new Nudix hydrolases have been found from Escherichia coli; one of them is Orf141, which cleaves pyrimidine deoxynucleoside triphosphates. Orf141 was cloned directly from E.,coli K1 strain and was overexpressed in E.,coli without any extra residues. Orf141 crystals were successfully obtained using polyethylene glycol 1500 as a precipitant at 285,K. X-ray diffraction data were collected to 3.1,Å resolution using synchrotron radiation. The crystal is a member of the rhombohedral space group H32, with unit-cell parameters a = b = 182.2, c = 62.3,Å, , = 90, , = 90, , = 120° (hexagonal setting). Two or three monomers are likely to be present in the asymmetric unit, with corresponding VM values of 2.92 and 1.95,Å3,Da,1 and solvent contents of 57.9 and 36.9%, respectively. [source]