Advertisement

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.

ENJOY UNLIMITED ACCES TO C&EN

Biological Chemistry

Radical Start For Iron-Sulfur Enzyme

Novel protein’s 4Fe-4S cluster generates an unusual reactive species to make a modified amino acid

by Carmen Drahl
June 21, 2010 | A version of this story appeared in Volume 88, Issue 25

A modified amino acid that is the target of diphtheria toxin is assembled through some unusual enzyme reactivity, a multi-institution team has found (Nature 2010, 465, 891). Researchers have known for decades about the molecular target, called diphthamide. But its biosynthesis had remained unclear. Steven E. Ealick, Jack Freed, and Hening Lin of Cornell University in collaboration with Carsten Krebs of Pennsylvania State University and coworkers have revealed the structure and chemistry of a novel iron-sulfur enzyme that they say catalyzes the first step of diphthamide biosynthesis in a microorganism. Diphtha­mide, which is found on a protein factor used during translation, is a histidine residue modified with help from the cofactor (S)-adenosyl methionine (SAM). The team’s work suggests the new enzyme’s 4Fe-4S cluster transfers an electron to SAM to generate a 3-amino-3-carboxypropyl radical intermediate, which goes toward making diphthamide. Similar iron-sulfur enzymes all generate a 5´-deoxyadenosyl radical from SAM instead, so the new enzyme represents “a remarkable adaptation of hallmark reactivity,” Krebs says. Eventually, the team hopes to understand how many different enzymes generate different reactive species from SAM.

Article:

This article has been sent to the following recipient:

0 /1 FREE ARTICLES LEFT THIS MONTH Remaining
Chemistry matters. Join us to get the news you need.