Allosteric enzymes, aspartate transcarbamylase, fructose-1 6-bisphosphatase, and chorismate mutase are under very active study of inhibition at both the active site and the regulatory site. The mechanisms of transmission of conformational information through large distances in the multi-subunit structures are being elucidated, using strongly-bound substrates and allosteric effectors or their analogues. Each is a key enzyme in a dominant metabolic pathway which is controlled by large conformational changes as the subunits shift their relative positions.
Selected Publications:
N. Sträter and W.N. Lipscomb (1995). Two-metal mechanism of bovine lens leucine aminopeptidase: Active site solvent structure and binding mode of L-leucinal, a gem-diolate transition state analogue, by X-ray crystallography. Biochemistry 34:14792-14800.
K.M. Reinisch, L. Chen, G.L. Verdine and W.N. Lipscomb (1995). The crystal structure of the Hae III methyltransferase covalently complexed to DNA: An extrahelical cytosine and rearranged base pairing. Cell 82:143-153.
Villeret, V., Huang, S., Zhang, Y., Xue, Y. and Lipscomb, W.N. (1995). Crystal structure of spinach chloroplast fructose-1,6-bisphosphatase at 2.8Å resolution. Biochemistry 34:4299-4306.