STRUCTURAL CHARACTERIZATION OF 2 SYNTHETIC CATALYSTS BASED ON ADIPOCYTE LIPID-BINDING PROTEIN

Adipocyte lipid-binding protein (ALBP) is a small (14.5 kDa) 10-strand ed beta-barrel protein found in mammalian fat cells, The crystal struc tures of various hole-farms of ALBP have been solved and show the fatt y acid ligand bound in a large (similar to 400 Angstrom(3)) cavity iso lated from bulk solvent. Examination of the cavity suggests that it wo uld be a good site for the creation of an artificial catalyst, as nume rous well defined crystal structures of ALBP are available and past st udies have shown the conformation to be reasonably tolerant to modific ation and mutagenesis. Previous work has shown ALBP to be a good prote in scaffold for exploring enantio- and stereoselective reactions; two constructs, ALBP attached to either a pyridoxamine or a phenanthroline group at C117, have been chemically characterized. Both modified prot eins have been crystallized and their structures solved and refined. T he X-ray models have been used to examine the origin of the chiral sel ectivity seen in the products. It is apparent that these covalent addu cts reduce the internal cavity volume, sterically limiting substrate i nteractions with the reactive groups, as well as solvent access to pot ential intermediates in the reaction pathway.