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Mechanism of allosteric regulation of transglutaminase 2 by GTP

Begg, Gillian E., Carrington, Lyle, Stokes, Philippa H., Matthews, Jacqueline M., Wouters, Merridee .A., Husain, Ahsan, Lorand, Laszlo, Iismaa, Siiri E. and Graham, Robert M. 2006, Mechanism of allosteric regulation of transglutaminase 2 by GTP, Proceedings of the national academy of sciences of the United States of America, vol. 103, no. 52, pp. 19683-19688, doi: 10.1073/pnas.0609283103.

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Title Mechanism of allosteric regulation of transglutaminase 2 by GTP
Author(s) Begg, Gillian E.
Carrington, Lyle
Stokes, Philippa H.
Matthews, Jacqueline M.
Wouters, Merridee .A.
Husain, Ahsan
Lorand, Laszlo
Iismaa, Siiri E.
Graham, Robert M.
Journal name Proceedings of the national academy of sciences of the United States of America
Volume number 103
Issue number 52
Start page 19683
End page 19688
Publisher National Academy of Sciences
Place of publication Washington, D. C.
Publication date 2006-12-26
ISSN 0027-8424
1091-6490
Keyword(s) protein conformation
GTP inhibition
transamidase activity
Summary 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 p-barrel 1 domain that harborst he GTP-bindings ite). Although not essential for GTP-mediated inhibition of cross-linking, this H bond enhances the rate of formation of the inactive conformer.
Language eng
DOI 10.1073/pnas.0609283103
Field of Research 060199 Biochemistry and Cell Biology not elsewhere classified
Socio Economic Objective 970106 Expanding Knowledge in the Biological Sciences
HERDC Research category C1.1 Refereed article in a scholarly journal
Copyright notice ©2006, National Academy of Sciences
Persistent URL http://hdl.handle.net/10536/DRO/DU:30038969

Document type: Journal Article
Collection: School of Life and Environmental Sciences
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