scholarly journals Insights into the slow-onset tight-binding inhibition ofEscherichia colidihydrofolate reductase: detailed mechanistic characterization of pyrrolo [3,2-f] quinazoline-1,3-diamine and its derivatives as novel tight-binding inhibitors

FEBS Journal ◽  
2015 ◽  
Vol 282 (10) ◽  
pp. 1922-1938 ◽  
Author(s):  
Bharath Srinivasan ◽  
Jeffrey Skolnick
Keyword(s):  
Tight Binding ◽  
Binding Inhibition ◽  
Slow Onset ◽  
Binding Inhibitors

Characterization and screening of tight binding inhibitors of xanthine oxidase: an on-flow assay

RSC Advances ◽  
2015 ◽  
Vol 5 (47) ◽  
pp. 37533-37538 ◽  
Author(s):  
M. V. N. Rodrigues ◽  
R. S. Corrêa ◽  
K. L. Vanzolini ◽  
D. S. Santos ◽  
A. A. Batista ◽  
...  
Keyword(s):  
Xanthine Oxidase ◽  
Tight Binding ◽  
Flow Characterization ◽  
Binding Inhibitors

On-flow characterization of tight binders of xanthine oxidase.

The design, synthesis, and characterization of tight-binding inhibitors of calmodulin

1985 ◽  
Vol 29 (2) ◽  
pp. 83-93 ◽  
Author(s):  
William F. DeGrado ◽  
Frank G. Prendergast ◽  
Henry R. Wolfe ◽  
Jos A. Cox
Keyword(s):  
Tight Binding ◽  
Synthesis And Characterization ◽  
Design Synthesis ◽  
Binding Inhibitors

scholarly journals Accurate quantitative determination of affinity and binding kinetics for tight binding inhibition of xanthine oxidase

2021 ◽  
Vol 139 ◽  
pp. 111664
Author(s):  
Haiyang Yang ◽  
Xueyan Li ◽  
Gang Li ◽  
Huating Huang ◽  
Wenning Yang ◽  
...  
Keyword(s):  
Quantitative Determination ◽  
Xanthine Oxidase ◽  
Tight Binding ◽  
Binding Kinetics ◽  
Binding Inhibition

scholarly journals Characterization of human pre-elafin mutants: full antipeptidase activity is essential to preserve lung tissue integrity in experimental emphysema

2007 ◽  
Vol 405 (3) ◽  
pp. 455-463 ◽  
Author(s):  
Alain Doucet ◽  
Dominique Bouchard ◽  
Marie France Janelle ◽  
Audrey Bellemare ◽  
Stéphane Gagné ◽  
...  
Keyword(s):  
Lung Tissue ◽  
Neutrophil Elastase ◽  
Tight Binding ◽  
Biochemical Properties ◽  
Van Der Waals Interactions ◽  
Tissue Destruction ◽  
Methionine Residue ◽  
Experimental Emphysema

Pre-elafin is a tight-binding inhibitor of neutrophil elastase and myeloblastin; two enzymes thought to contribute to tissue damage in lung emphysema. Previous studies have established that pre-elafin is also an effective anti-inflammatory molecule. However, it is not clear whether both functions are linked to the antipeptidase activity of pre-elafin. As a first step toward elucidating the structure/function relationship of this protein, we describe here the construction and characterization of pre-elafin variants with attenuated antipeptidase potential. In these mutants, the P1′ methionine residue of the inhibitory loop is replaced by either a lysine (pre-elafinM25K) or a glycine (pre-elafinM25G) residue. Both mutated variants are stable and display biochemical properties undistinguishable from WT (wild-type) pre-elafin. However, compared with WT pre-elafin, their inhibitory constants are increased by one to four orders of magnitude toward neutrophil elastase, myeloblastin and pancreatic elastase, depending on the variants and enzymes tested. As suggested by molecular modelling, this attenuated inhibitory potential correlates with decreased van der Waals interactions between the variants and the enzymes S1′ subsite. In elastase-induced experimental emphysema in mice, only WT pre-elafin protected against tissue destruction, as assessed by the relative airspace enlargement measured using lung histopathological sections. Pre-elafin and both mutants prevented transient neutrophil alveolitis. However, even the modestly affected pre-elafinM25K mutant, as assayed in vitro with small synthetic substrates, was a poor inhibitor of the neutrophil elastase and myeloblastin elastolytic activity measured with insoluble elastin. We therefore conclude that full antipeptidase activity of pre-elafin is essential to protect against lung tissue lesions in this experimental model.

scholarly journals Theoretical treatment of tight-binding inhibition of an enzyme. Ribonuclease inhibitor as special case

1988 ◽  
Vol 253 (2) ◽  
pp. 517-522 ◽  
Author(s):  
J M Fominaya ◽  
J M García-Segura ◽  
M Ferreras ◽  
J G Gavilanes
Keyword(s):  
Tight Binding ◽  
Theoretical Treatment ◽  
Inhibitor Protein ◽  
Ribonuclease Inhibitor ◽  
Rat Testis ◽  
Binding Inhibition ◽  
Different Types ◽  
Functional Consequences ◽  
Inhibitor System ◽  
Special Case

A general treatment of very tight-binding inhibition is described. It was applied to purified endogenous RNAase inhibitor from rat testis. This treatment discriminates among the different types of inhibition and allows for calculation of the inhibition parameters. When very tight-binding inhibitions are studied at similar molar concentrations of both enzyme and inhibitor, a further approach is required. This is also described and applied to the RNAase inhibitor. A Ki value of 3.2 x 10(-12) M was found for this inhibitor protein. On the basis of this result, it was considered inappropriate to classify this type of inhibitor in terms of competitive or non-competitive, as has been done for such inhibitors so far. Functional consequences of this analysis are discussed for the RNAase-RNAase inhibitor system.

Estimating KI values for tight binding inhibitors from dose-response plots

1995 ◽  
Vol 5 (17) ◽  
pp. 1947-1952 ◽  
Author(s):  
Robert A. Copeland ◽  
Diane Lombardo ◽  
John Giannaras ◽  
Carl P. Decicco
Keyword(s):  
Dose Response ◽  
Tight Binding ◽  
Binding Inhibitors

Slow- and tight-binding inhibitors of the 85-kDa human phospholipase A2

Biochemistry ◽  
1993 ◽  
Vol 32 (23) ◽  
pp. 5935-5940 ◽  
Author(s):  
Ian P. Street ◽  
Hung Kuei Lin ◽  
France Laliberte ◽  
Farideh Ghomashchi ◽  
Zhaoyin Wang ◽  
...  
Keyword(s):  
Phospholipase A2 ◽  
Tight Binding ◽  
Binding Inhibitors
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