Crystal structures of the peanut lectin-lactose complex at acidic pH: Retention of unusual quaternary structure, empty and carbohydrate bound combining sites, molecular mimicry and crystal packing directed by interactions atthe combining site

The crystal structures of a monoclinic and a triclinic form of the peanut l ectin-lactose complex, grown at pH 4.6, have been determined. They contain two and one crystallographically independent tetramers, respectively. The u nusual "open" quaternary structure of the lectin, observed in the orthorhom bic complex grown in neutral pH, is retained at the acidic pH, The sugar mo lecule is bound to three of the eight subunits in the monoclinic crystals, whereas the combining sites in four are empty. The lectin-sugar interaction s are almost the same at neutral and acidic pH, A comparison of the sugar-b ound and free subunits indicates that the geometry of the combining site is relatively unaffected by ligand binding. The combining site of the eighth subunit in the monoclinic crystals is bound to a peptide stretch in a loop from a neighboring molecule. The same interaction exists in two subunits of the triclinic crystals, whereas density corresponding to sugar exists in t he combining sites of the other two subunits, Solution studies show that ol igopeptides with sequences corresponding to that in the loop bind to the Le ctin at acidic pH, but only with reduced affinity at neutral pH, The revers e is the case with the binding of lactose to the lectin, A comparison of th e neutral and acidic pH crystal structures indicates that the molecular pac king in the latter is directed to a substantial extent by the increased aff inity of the peptide loop to the combining site at acidic pH. (C) 2001 Wile y-Liss, Inc.