scholarly journals Cross-talk between the Allosteric Effector-binding Sites in Mouse Ribonucleotide Reductase

2000 ◽  
Vol 275 (42) ◽  
pp. 33021-33026 ◽  
Author(s):  
Peter Reichard ◽  
Rolf Eliasson ◽  
Rolf Ingemarson ◽  
Lars Thelander
Keyword(s):  
Cross Talk ◽  
Ribonucleotide Reductase ◽  
Binding Sites ◽  
Allosteric Effector ◽  
Effector Binding

scholarly journals Analysis of Allosteric Effector Binding Sites of Potato ADP-glucose Pyrophosphorylase through Reverse Genetics

2001 ◽  
Vol 276 (44) ◽  
pp. 40834-40840 ◽  
Author(s):  
I. Halil Kavakli ◽  
Jong-Sug Park ◽  
Casey J. Slattery ◽  
Peter R. Salamone ◽  
Jennifer Frohlick ◽  
...  
Keyword(s):  
Binding Sites ◽  
Reverse Genetics ◽  
Allosteric Effector ◽  
Adp Glucose Pyrophosphorylase ◽  
Effector Binding

Alterations in the components of ribonucleotide reductase in hydroxyurea-resistant hamster cells

1983 ◽  
Vol 3 (8) ◽  
pp. 741-748 ◽  
Author(s):  
Jim A. Wright ◽  
Joseph G. Cory
Keyword(s):  
Ribonucleotide Reductase ◽  
Reductase Activity ◽  
Antitumor Agent ◽  
Resistant Cell ◽  
Resistant Cell Line ◽  
Wild Type ◽  
Type Analysis ◽  
Similar Mode ◽  
Ribonucleotide Reductase Activity ◽  
Effector Binding

Two components of mammalian ribonucleotide reductase have been separated by blue dextran-Sepharose chromatography from a hydroxyurea-resistant cell line, NcR-30A2, and its parental wild type. Analysis of reductase activity in these cells and the enzyme components reveals that there are three alterations involving ribonucleotide reductase activity in NcR-30A2 cells. There is an elevation in the effector-binding (EB) component, an elevation in the non-heine-ironcontaining (NHI) component, and an alteration in the NHI component that renders the enzyme less sensitive to inhibition by hydroxyurea. These findings easily account for the resistance of NcR-30A2 cells to the antitumor agent hydroxyurea, and to other drugs with a similar mode of action.

scholarly journals Functional tunability from a distance: Rheostat positions influence allosteric coupling between two distant binding sites

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Tiffany Wu ◽  
Liskin Swint-Kruse ◽  
Aron W. Fenton
Keyword(s):  
Binding Sites ◽  
Functional Outcomes ◽  
Human Liver ◽  
Full Range ◽  
Allosteric Coupling ◽  
Multiple Parameters ◽  
Wide Range ◽  
Allosteric Binding Sites ◽  
Fructose 1,6 Bisphosphate ◽  
Effector Binding

AbstractFor protein mutagenesis, a common expectation is that important positions will behave like on/off “toggle” switches (i.e., a few substitutions act like wildtype, most abolish function). However, there exists another class of important positions that manifests a wide range of functional outcomes upon substitution: “rheostat” positions. Previously, we evaluated rheostat positions located near the allosteric binding sites for inhibitor alanine (Ala) and activator fructose-1,6-bisphosphate (Fru-1,6-BP) in human liver pyruvate kinase. When substituted with multiple amino acids, many positions demonstrated moderate rheostatic effects on allosteric coupling between effector binding and phosphoenolpyruvate (PEP) binding in the active site. Nonetheless, the combined outcomes of all positions sampled the full range of possible allosteric coupling (full tunability). However, that study only evaluated allosteric tunability of “local” positions, i.e., positions were located near the binding sites of the allosteric ligand being assessed. Here, we evaluated tunability of allosteric coupling when mutated sites were distant from the allosterically-coupled binding sites. Positions near the Ala binding site had rheostatic outcomes on allosteric coupling between Fru-1,6-BP and PEP binding. In contrast, positions in the Fru-1,6-BP site exhibited modest effects on coupling between Ala and PEP binding. Analyzed in aggregate, both PEP/Ala and PEP/Fru-1,6-BP coupling were again fully tunable by amino acid substitutions at this limited set of distant positions. Furthermore, some positions exhibited rheostatic control over multiple parameters and others exhibited rheostatic effects on one parameter and toggle control over a second. These findings highlight challenges in efforts to both predict/interpret mutational outcomes and engineer functions into proteins.

scholarly journals Mapping of Effector Binding Sites of Transducin α-Subunit Using Gαt/GαilChimeras

1996 ◽  
Vol 271 (1) ◽  
pp. 413-424 ◽  
Author(s):  
Nikolai P. Skiba ◽  
Hyunsu Bae ◽  
Heidi E. Hamm
Keyword(s):  
Binding Sites ◽  
Α Subunit ◽  
Effector Binding
Sign in / Sign up

Export Citation Format

Share Document