August 21, 1998—Starting with the structure of a common bacterial enzyme, a team of investigators from the Howard Hughes Medical Institute at The Rockefeller University has unlocked the structural secrets at the heart of some of life's most important biological processes.

Using x-ray crystallography, HHMI investigator Stephen K. Burley and his colleagues, working with Alex Vassilev, Yasutaka Makino and Yoshihiro Nakatani of the National Institute of Child Health and Human Development, have generated the three-dimensional molecular structure of a common enzyme, known as aminoglycoside 3-N-acetyltransferase, from the bacterium Serratia marcescens. The research is reported in the August 21, 1998, issue of the journal Cell.

According to Burley, this work has far-reaching repercussions because the bacterial enzyme's structure is shared by a superfamily of at least 150 enzymes present in every kingdom of life. Across the members of this family, says Burley, minor differences on the surfaces of the molecules generate small changes in structure, allowing them to perform a variety of biological functions.

The HHMI team determined that the bacterial enzyme's structure resembles "a cupped right hand wrapped around a cylinder." Named in part for its function, the enzyme promotes the transfer of an acetyl group from a donor molecule to a recipient molecule. "The three-dimensional structure shows us how the enzyme positions both the donor and the recipient so that the transfer can occur," Burley says.

Using a technique called "threading," Burley's team, which included Rockefeller scientists Eva Wolf and Andrej Sali, used the structure of the single enzyme they discerned to examine other members of the family of enzymes without actually having to complete x-ray crystallography on each complex. "Essentially, we thread the amino acid sequence of the unknown structures through the structure of th
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Contact: Jim Keeley
keeleyj@hhmi.org
(301) 215-8858
Howard Hughes Medical Institute
21-Aug-1998