First-ever designer protein fits like a glove

日期:2019-02-26 12:03:01 作者:萧谫瘾 阅读:

By Bob Holmes A MOLECULAR tailor’s shop has turned out the world’s first made-to-order protein. The feat opens the door to a future in which scientists might design bespoke proteins for drugs or industrial catalysts. A protein is a long chain of amino acid building blocks, tightly folded on itself like a scrunched-up piece of string. Electrically charged parts remain exposed to surrounding water molecules, while neutral parts are tucked away inside. With interactions between many thousands of atoms, proteins are so complex that scientists have not been able to predict their folded shapes from their amino acid sequences. Now, after five years of studying the complex atomic interactions in proteins, Stephen Mayo of the California Institute of Technology in Pasadena has developed a computer program that selects the sequence of amino acids required to yield a folded protein of a specific shape. With his colleague Bassil Dahiyat, he has used the program to create the first fully tailored protein. The protein, containing 28 amino acids, could be put together in 1027 different ways. But the researchers used the program to predict the sequence that would give a shape that mimics an existing protein type called the “zinc finger”. In last week’s Science (vol 278, p 82), the researchers say that when they synthesised the protein, it fitted the zinc-finger shape almost perfectly—proof that protein design is really possible. “This will stand as a landmark piece of work,” says Jim Wells, a protein engineer at Genentech in San Francisco. Mayo hopes eventually to design proteins up to 150 amino acids long, the size of most natural proteins. This would enable biotechnologists to design heat-stable enzymes for industry and make more effective drugs. “It would be an awesome achievement to design a protein that would do what you want it to,