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Mechanism of allosteric regulation of transglutaminase 2 by GTP
- Source :
- Proceedings of the National Academy of Sciences. 103:19683-19688
- Publication Year :
- 2006
- Publisher :
- Proceedings of the National Academy of Sciences, 2006.
-
Abstract
- Allosteric regulation is a fundamental mechanism of biological control. Here, we investigated the allosteric mechanism by which GTP inhibits cross-linking activity of transglutaminase 2 (TG2), a multifunctional protein, with postulated roles in receptor signaling, extracellular matrix assembly, and apoptosis. Our findings indicate that at least two components are involved in functionally coupling the allosteric site and active center of TG2, namely ( i ) GTP binding to mask a conformationally destabilizing switch residue, Arg-579, and to facilitate interdomain interactions that promote adoption of a compact, catalytically inactive conformation and ( ii ) stabilization of the inactive conformation by an uncommon H bond between a cysteine (Cys-277, an active center residue) and a tyrosine (Tyr-516, a residue located on a loop of the β-barrel 1 domain that harbors the GTP-binding site). Although not essential for GTP-mediated inhibition of cross-linking, this H bond enhances the rate of formation of the inactive conformer.
- Subjects :
- Models, Molecular
GTP'
Stereochemistry
Allosteric regulation
Arginine
Active center
Protein structure
GTP-binding protein regulators
Allosteric Regulation
GTP-Binding Proteins
Animals
Protein Glutamine gamma Glutamyltransferase 2
Cysteine
Disulfides
Binding site
Binding Sites
Transglutaminases
Multidisciplinary
biology
Chemistry
Extracellular matrix assembly
Water
Hydrogen Bonding
Biological Sciences
Protein Structure, Tertiary
Rats
Allosteric enzyme
Mutation
biology.protein
Tyrosine
Guanosine Triphosphate
Protein Binding
Subjects
Details
- ISSN :
- 10916490 and 00278424
- Volume :
- 103
- Database :
- OpenAIRE
- Journal :
- Proceedings of the National Academy of Sciences
- Accession number :
- edsair.doi.dedup.....4d5c6104d65612ff9d99b1753c529387