C&EN logo The Newsmagazine of the Chemical World
Home Current Issue ChemJobs Join ACS
Support
Latest News
Business
Government & Policy
Science/Technology
Careers and Employment
ACS News
topics
   
Support
 
Support
How to log in
Contact Us
Site Map
   
About C&EN
About the Magazine
How to Subscribe
How to Advertise
Chemcyclopedia

Latest News RSS Feed

latest news RSS feedWhat is this?

   
Join ACS
Join ACS
  Latest News  
  June 21, 2005  

BIOCHEMISTRY

  Lead Binding Reexamined
Trigonal pyramidal coordination to sulfur may be key to mechanism of lead poisoning
 

DAVID BARRY
   
 
 

Lead poisoning may be due to an unanticipated coordination geometry for lead in sulfur-rich sites, a new study suggests.

In the past decade, biologists have found evidence that low levels of lead can cause developmental disorders in children by disrupting the function of regulatory proteins called transcription factors. The prevailing hypothesis is that lead displaces zinc from sulfur-rich structural binding pockets in the proteins, causing them to fold improperly. Yet a detailed chemical understanding of how lead acts differently from zinc to reshape and disable the proteins has been lacking.

A new study shows that lead preferentially binds to only three sulfurs in a trigonal pyramidal configuration, even when additional sulfurs are available (J. Am. Chem. Soc. 2005, 127, 9495). Zinc, on the other hand, binds sulfur in a four-coordinate, tetrahedral fashion. A team of scientists led by chemistry professor Hilary A. Godwin and graduate student John S. Magyar at Northwestern University, along with chemistry professor James E. Penner-Hahn and his group at the University of Michigan, carried out the work.

LEAD BINDS THREE Godwin (left) and Magyar helped discover that lead coordinates three sulfurs in structural binding sites of proteins even when four sulfurs are available, unlike zinc, which uses tetrahedral coordination. When the zinc in proteins is substituted with lead, the resulting proteins cannot function.
Photo by Matthew Gilson

Godwin says the observed difference in binding explains how lead could cause improper protein folding. That lead would coordinate with sulfur-rich binding sites in a trigonal fashion even when four thiol groups are available “never occurred to us,” Godwin says. “The chemical literature has widely suggested that lead binds sulfur in a four-coordinate fashion.”

The new findings are based in part on studies of the coordination geometry of lead in lead-substituted proteins as examined by X-ray absorption spectroscopy. The spectra of the proteins closely match that of a model compound, in which lead is known to have three-coordinate chemistry, obtained by coauthor and Columbia University chemistry professor Gerard Parkin. The “nearly identical” spectra indicate that the coordination geometries of lead in the proteins and in the model compound are similar, the authors say.
 
     
  Chemical & Engineering News
ISSN 0009-2347
Copyright © 2005
 


 
E-mail the editor