Nailing the LacY mechanism

Credit: © 2003 AAAS 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, nonaggregatin

By | February 1, 2006

<figcaption> Credit: © 2003 AAAS</figcaption>
Credit: © 2003 AAAS

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 of the sugar against its gradient by coupling it to the movement of the proton down its own gradient.

While evidence continues to mount in favor of the alternating access theory, Kaback says the structure of the outward-facing LacY conformation must be solved in order to ?really nail? the proof.

Reference

1. J. Abramson et al., ?Structure and mechanism of the lactose permease of Escherichia coli,? Science, 301:610?5, 2003. (Cited in 212 papers)

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