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Biological Chemistry

Megaenzyme Crystal Structure Unveiled

The X-ray structure of a 750-kilodalton bacterial carboxylase should provide clues about human diseases

by Celia Henry Arnaud
August 23, 2010 | A version of this story appeared in Volume 88, Issue 34

Credit: Liang Tong
Top view (top) and side view (bottom) of the bacterial PCC enzyme.
Credit: Liang Tong
Top view (top) and side view (bottom) of the bacterial PCC enzyme.

A team led by Liang Tong of Columbia University is reporting a 3.2-Å X-ray crystal structure of the 750-kilodalton bacterial enzyme propionyl-coenzyme A carboxylase (PCC), a feat that is anticipated to provide clues about human diseases (Nature 2010, 466, 1001). The bacterial protein consists of six α subunits containing the biotin carboxylase (BC) and biotin carboxyl carrier protein domains and six β subunits containing the carboxyltransferase (CT) domain. The crystal structure reveals that the enzyme consists of a central, cylindrical β6 hexamer core decorated with three α subunits at both ends. The BC and CT active sites are separated by about 55 Å, and a previously unknown domain in the α subunits mediates interactions between them. Cryoelectron microscopy studies at 15-Å resolution suggest that human PCC has a structure similar to that of the bacterial enzyme. The structure could help uncover the molecular basis of disease-causing mutations in human PCC, the researchers note. For example, deficiencies in the human version are associated with propionic acidemia, a potentially fatal recessive genetic disorder. The structure could also provide insight into other biotin-dependent carboxylases, they add.


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