1k8n

From Proteopedia

proteopedia linkproteopedia link

Template:STRUCTURE 1k8n

NMR STRUCTURE OF THE XBY2 DNA DUPLEX, AN ANALOG OF CK14 CONTAINING PHOSPHORODITHIOATE GROUPS AT C22 AND C24

Overview

A variety of monothio- and dithiosubstituted duplex aptamers targeting NF-kappaB have been synthesized and designed. The specificity and affinity of the dithioate aptamers of p50 and RelA(p65) NF-kappaB homodimers was determined by gel shift experiments. The NMR solution structures for several unmodified and dithioate backbone modified 14-base paired duplex aptamers have been determined by a hybrid, complete matrix (MORASS)/restrained molecular dynamics method. Structural perturbations of the dithioate substitutions support our hypothesis that the dithioate binds cations less tightly than phosphoryl groups. This increases the electrostatic repulsion across the B-form narrow minor groove and enlarges the minor groove, similar to that found in A-form duplexes. Structural analysis of modeled aptamer complexes with NF-kappaB homo- and heterodimers suggests that the dithioate backbone substitution can increase the aptamer's relative affinity to basic groups in proteins such as NF-kappaB by helping to "strip" the cations from the aptamer backbone.

About this Structure

Full crystallographic information is available from OCA.

Reference

Solution structure and design of dithiophosphate backbone aptamers targeting transcription factor NF-kappaB., Volk DE, Yang X, Fennewald SM, King DJ, Bassett SE, Venkitachalam S, Herzog N, Luxon BA, Gorenstein DG, Bioorg Chem. 2002 Dec;30(6):396-419. PMID:12642125 Page seeded by OCA on Fri May 2 22:26:18 2008