Fragment-based identification of determinants of conformational and spectroscopic change at the ricin active site.

ABSTRACT:

Background

Ricin is a potent toxin and known bioterrorism threat with no available antidote. The ricin A-chain (RTA) acts enzymatically to cleave a specific adenine base from ribosomal RNA, thereby blocking translation. To understand better the relationship between ligand binding and RTA active site conformational change, we used a fragment-based approach to find a minimal set of bonding interactions able to induce rearrangements in critical side-chain positions.

Results

We found that the smallest ligand stabilizing an open conformer of the RTA active site pocket was an amide group, bound weakly by only a few hydrogen bonds to the protein. Complexes with small amide-containing molecules also revealed a switch in geometry from a parallel towards a splayed arrangement of an ar

SUBMITTER: Carra JH 

PROVIDER: S-EPMC2194779 | biostudies-literature | 2007 Nov

REPOSITORIES: biostudies-literature