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. Attached Files Name Description MIMEType Size Downloads 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 Collections: Faculty of Science, Engineering and Built Environment School of Life and Environmental Sciences Related Links Link Description Connect to published version (restricted access) Go to link with your DU access privileges     Unless expressly stated otherwise, the copyright for items in DRO is owned by the author, with all rights reserved. Versions Version Filter Type Mon, 24 Oct 2011, 08:08:04 EST Tue, 25 Oct 2011, 15:10:17 EST Tue, 25 Oct 2011, 15:12:06 EST Thu, 03 Nov 2011, 08:44:54 EST Wed, 13 Nov 2013, 13:27:20 EST Mon, 16 Jun 2014, 18:59:15 EST Fri, 08 Nov 2019, 00:36:59 EST Sat, 02 Apr 2022, 23:37:06 EST Filtered Full Citation counts:   Cited 98 times in TR Web of Science Cited 106 times in Scopus Search Google Scholar Access Statistics: 395 Abstract Views, 1 File Downloads  -  Detailed Statistics Created: Mon, 24 Oct 2011, 08:08:04 EST