If you have an ACS member number, please enter it here so we can link this account to your membership. (optional)

ACS values your privacy. By submitting your information, you are gaining access to C&EN and subscribing to our weekly newsletter. We use the information you provide to make your reading experience better, and we will never sell your data to third party members.


Biological Chemistry

Acrobatic HIV Enzyme Caught In Action

New mechanistic finding on reverse transcriptase???s sliding and flipping catalytic motions could help advance AIDS drug design

by Stuart A. Borman
November 17, 2008 | A version of this story appeared in Volume 86, Issue 46

New mechanistic findings on a key HIV enzyme could help advance AIDS drug design, according to a report in Science (2008, 322, 1092). Reverse transcriptase (RT) is an essential enzyme in the life cycle of HIV and a target of AIDS drugs such as azidothymidine (AZT). But aspects of RT's mechanism have remained a mystery. Although the mechanism has been studied by crystallography and other techniques, the acrobatic moves RT undergoes while converting HIV's RNA genome into DNA for incorporation into host cells have been hard to follow. Harvard University's Xiaowei Zhuang and coworkers have now carried out a painstaking study using fluorescence resonance energy transfer—a technique with a powerful ability to probe intermolecular interactions—was used to analyze RT's catalytic pathway. The study shows how RT slides along its nucleic acid substrates and flips into binding orientations that support different catalytic functions. An independent commentary in the same issue of Science notes that the work "vividly illustrates that RT has a remarkable dynamic flexibility that contributes to more efficient replication."


This article has been sent to the following recipient:

Chemistry matters. Join us to get the news you need.