Researchers including H. Ronald Kaback of the University of California, Los Angeles, had been attempting for more than a decade to crystallize LacY, the lactose permease of Escherichia coli. ?After hitting my head against the wall with the wild type, it occurred to me that it might be a good idea to try the mutant,? Kaback writes in an E-mail.
In the early 1980s Kaback had stumbled upon a thermostable, nonaggregating mutant form of the protein trapped in its cytoplasm-facing conformation during an attempt to make a functional cysteine-free protein. He sent the sample to So Iwata at Imperial College London, who succeeded in growing the crystals. In 2003, the teams? 3.5 angstrom structure substantiated previous hints of its ?alternating access? cotransport mechanism.1 In this model, a single binding site in LacY opens outward to bind lactose and H+ and then opens inward to release them, thereby powering the movement ...
