Transglutaminase 2 Undergoes A Large Conformational Change Upon Activation

Main Category: Biology / Biochemistry
Article Date: 17 Dec 2007 - 17:00 PDT

email to a friend   printer friendly   view / write opinions   rate article

The transglutaminase family of enzymes is best known for crosslinking proteins to form networks that strengthen tissues. Although this enzyme family has been extensively studied, a detailed understanding of the catalytic mechanism has been hampered by the lack of a structure in which the enzyme is active.

This week in the open-access journal PLoS Biology, Daniel Pinkas, Chaitan Khosla, and colleagues show how they have solved, at atomic resolution, the structure of transglutaminase 2 (TG2) in complex with a molecule that mimics a natural substrate. The structure exposes the active site, giving direct insights into the catalytic mechanism. Unexpectedly, they observed a very large conformational change with respect to previous transglutaminase structures. Very few proteins have been observed to undergo this type of large-scale transformation.

They propose a role for this structural rearrangement in the early stages of celiac disease, an autoimmune disorder in which TG2 is the principal auto-antigen. Besides the fundamental implications, these results should allow for the rational design of better inhibitors of TG2 for pharmacological and therapeutic purposes.

Citation: Pinkas DM, Strop P, Brunger AT, Khosla C (2007) Transglutaminase 2 undergoes a large conformational change upon activation. PLoS Biol 5(12): e327. doi:10.1371/journal.pbio.0050327 Please click here

http://www.plosbiology.org

Public Library of Science
185 Berry Street, Suite 3100
San Francisco, CA 94107
USA