Conformational Coupling of Mg2+and Ca2+on the Three-State Folding of Calexcitin B†

Biochemistry ◽  
2003 ◽  
Vol 42 (18) ◽  
pp. 5531-5539 ◽  
Author(s):  
Zoltan Gombos ◽  
Isabelle Durussel ◽  
Mitsuhiko Ikura ◽  
David R. Rose ◽  
Jos A. Cox ◽  
...  
Keyword(s):  
Conformational Coupling

scholarly journals Evidence for conformational coupling between two calcium channels

2004 ◽  
Vol 101 (34) ◽  
pp. 12748-12752 ◽  
Author(s):  
C. Paolini ◽  
J. D. Fessenden ◽  
I. N. Pessah ◽  
C. Franzini-Armstrong
Keyword(s):  
Calcium Channels ◽  
Conformational Coupling

Conformational Coupling and trans-Inhibition in the Human Antigen Transporter Ortholog TmrAB Resolved with Dipolar EPR Spectroscopy

2018 ◽  
Vol 140 (13) ◽  
pp. 4527-4533 ◽  
Author(s):  
Katja Barth ◽  
Susanne Hank ◽  
Philipp E. Spindler ◽  
Thomas F. Prisner ◽  
Robert Tampé ◽  
...  
Keyword(s):  
Epr Spectroscopy ◽  
Conformational Coupling

scholarly journals The activation loop and substrate-binding cleft of glutaminase C are allosterically coupled

2019 ◽  
Vol 295 (5) ◽  
pp. 1328-1337
Author(s):  
Yunxing Li ◽  
Sekar Ramachandran ◽  
Thuy-Tien T. Nguyen ◽  
Clint A. Stalnecker ◽  
Richard A. Cerione ◽  
...  
Keyword(s):  
Substrate Binding ◽  
Fluorescence Emission ◽  
Reciprocal Relationship ◽  
Tryptophan Residue ◽  
Substrate Affinity ◽  
Activation Loop ◽  
Conformational Coupling ◽  
Binding Cleft ◽  
Glutaminase Activity

The glutaminase C (GAC) isoform of mitochondrial glutaminase is overexpressed in many cancer cells and therefore represents a potential therapeutic target. Understanding the regulation of GAC activity has been guided by the development of spectroscopic approaches that measure glutaminase activity in real time. Previously, we engineered a GAC protein (GAC(F327W)) in which a tryptophan residue is substituted for phenylalanine in an activation loop to explore the role of this loop in enzyme activity. We showed that the fluorescence emission of Trp-327 is enhanced in response to activator binding, but quenched by inhibitors of the BPTES class that bind to the GAC tetramer and contact the activation loop, thereby constraining it in an inactive conformation. In the present work, we took advantage of a tryptophan substitution at position 471, proximal to the GAC catalytic site, to examine the conformational coupling between the activation loop and the substrate-binding cleft, separated by ∼16 Å. Comparison of glutamine binding in the presence or absence of the BPTES analog CB-839 revealed a reciprocal relationship between the constraints imposed on the activation loop position and the affinity of GAC for substrate. Binding of the inhibitor weakened the affinity of GAC for glutamine, whereas activating anions such as Pi increased this affinity. These results indicate that the conformations of the activation loop and the substrate-binding cleft in GAC are allosterically coupled and that this coupling determines substrate affinity and enzymatic activity and explains the activities of CB-839, which is currently in clinical trials.

Conformational coupling of integrin and Thy-1 regulates Fyn priming and fibroblast mechanotransduction

2015 ◽  
Vol 146 (5) ◽  
pp. 1465OIA57
Author(s):  
Vincent F. Fiore ◽  
Patrick W. Strane ◽  
Anton V. Bryksin ◽  
Eric S. White ◽  
James S. Hagood ◽  
...  
Keyword(s):  
Conformational Coupling

scholarly journals Conformational coupling by trans-phosphorylation in calcium calmodulin dependent kinase II

2019 ◽  
Vol 15 (5) ◽  
pp. e1006796 ◽  
Author(s):  
Alessandro Pandini ◽  
Howard Schulman ◽  
Shahid Khan
Keyword(s):  
Calcium Calmodulin Dependent ◽  
Conformational Coupling
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