NEWS OF THE WEEK BIOINORGANIC
CHEMISTRY
LEAD BINDING REEXAMINED Trigonal pyramidal coordination to sulfur may be key to lead poisoning
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EAD POISONING MAY BE DUE
to an unanticipated coordina tion geometry for lead in sul fur-rich sites, a new study suggests. In the past decade, biologists have found evidence that low lev els of lead can cause develop mental disorders in children by disrupting the function of regu latory proteins called transcrip tion factors. The prevailing hy pothesis is that lead displaces zinc from sulfur-rich structural bind ing pockets in the proteins, caus ing them to fold improperly Ifet a detailed chemical understand ing 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 addi tional sulfurs are available (J.Am. Chem. Soc. 2 0 0 5 , 127, 9495). Zinc, on the other hand, binds sulfur in a four-coordinate, tetrahedral fashion. A team of scien tists led by chemistry professor Hilary A. Godwin and graduate studentJohn S. Magyar at North western University, along with chemistry professor James E. Penner-Hahn and his group at the University of Michigan, carried out the work. Godwin says the observed dif ference in binding explains how lead could cause improper pro tein folding. That lead would co ordinate with sulfur-rich binding sites in a trigonal fashion even when four thiol groups are avail able "never occurred to us," God win says. "The chemical literature has widely suggested that lead binds sulfur in a four-coordinate fashion." WWW.CEN-0NLINE.ORG
The new findings are based in part on studies of the coordina tion geometry of lead in lead-sub stituted proteins as examined by X-ray absorption spectroscopy The spectra of the proteins close ly match that of a model com pound in which lead is known to have three-coordinate chemistry obtained by coauthor and Co lumbia University chemistry pro fessor Gerard Parkin. The "nearINTERNATIONAL
LEAD BINDS THREE 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.
ly identical" spectra indicate that the coordination geometries of lead in the proteins and in the model compound are similar, the authors say— DAVID BARRY C O M P E T I T I O N
U.S. Chemistry Olympiad Team Finalized •our high school students have been se lected to represent the U.S. at the 36th International Chemistry Olympiad in Taipei from July 16 to 25. Allen Cheng of Arcadia High School, Arca dia, Calif.; Scott Rabin of Miami Palmetto Se-
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I Ν T R A I N I N G Before Cheng was selected for the U.S. chemistry olympiad teamp he attended an intense study camp with 19 other high school students.
nior High School, Miami; Jacob Sanders of the Academy for the Advancement of Science & Technology, River Edge, N.J.; and Nicholas Sofroniew of Harvard-Westlake High School, Los Angeles, will compete with representa tives from more than 60 nations. Michael Blaisse of Bishop McDevitt High School, Harrisburg, Pa., and Andrew Freddo of Manalapan High School, Colts Neck, N.J., will serve as alternates. The team was chosen after an intense twoweek study camp at the U.S. Air Force Acade my in Colorado for 20 students who scored especially well in regional competitions. The camp featured college-level training, empha sizing organic chemistry, with mentors Roxana (Roxie) Allen, a chemistry teacher at St. John School, Houston; John C. Kotz, distin guished teaching professorat State Universi ty of New York College, Oneonta; and Nadine Szczepanski, a chemistry professor at MacMurray College, Jacksonville, III. In Taipei, the team members will compete in both theoretical and practical chemistry competitions, and they will also sightsee, so cialize, and tour local chemistry facilities. Allen and Szczepanski, the head mentor, will accompany the team. ACS has helped sponsor the U.S. olympiad team every year since 1984.—AALOK MEHTA
C & E N / J U N E 2 7 , 2005
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