cover illustration The binding of a non-natural ligand to a monomeric variant of TIM.The picture shows the mode of binding of citrate (CA) in its omit-density of an (Fo-Fc)αc map. In this new variant (A-TIM) the phosphate binding loop region has been changed and shortened, providing space for the binding of the carboxylate moiety of citrate, which points into the new binding pocket between loop-7 and loop-8.The side chains of the catalytic residues (Asn11, Lys13, His95, Glu167) are also shown. In wild type TIM the loops 6, 7 and 8 sequester the phosphate moiety of the substrate. Because of the shortened and modified loop-8, the new variant has completely new binding properties. Further details, including binding studies with a substrate analogue and a suicide inhibitor, are described in the manuscript by Alahuhta et al., pp. 257-266.
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