Optimization of Substrate-Analogue Furin Inhibitors

ChemMedChem ◽  
2017 ◽  
Vol 12 (23) ◽  
pp. 1953-1968 ◽  
Author(s):  
Teodora Ivanova ◽  
Kornelia Hardes ◽  
Stephanie Kallis ◽  
Sven O. Dahms ◽  
Manuel E. Than ◽  
...  
Keyword(s):  
Substrate Analogue

Rescuing of the hydride transfer reaction in the Glu312Asp variant of choline oxidase by a substrate analogue

2010 ◽  
Vol 499 (1-2) ◽  
pp. 1-5 ◽  
Author(s):  
Osbourne Quaye ◽  
Tranbao Nguyen ◽  
Swathi Gannavaram ◽  
Andrea Pennati ◽  
Giovanni Gadda
Keyword(s):  
Transfer Reaction ◽  
Hydride Transfer ◽  
Choline Oxidase ◽  
Substrate Analogue ◽  
Hydride Transfer Reaction

scholarly journals Three-dimensional Structure of l-2-Haloacid Dehalogenase fromXanthobacter autotrophicusGJ10 Complexed with the Substrate-analogue Formate

1997 ◽  
Vol 272 (52) ◽  
pp. 33015-33022 ◽  
Author(s):  
Ivo S. Ridder ◽  
Henriëtte J. Rozeboom ◽  
Kor H. Kalk ◽  
Dick B. Janssen ◽  
Bauke W. Dijkstra
Keyword(s):  
Three Dimensional ◽  
Dimensional Structure ◽  
Haloacid Dehalogenase ◽  
Three Dimensional Structure ◽  
Substrate Analogue

scholarly journals Correlation of Vesicle Binding and Phospholipid Dynamics with Phospholipase C Activity

2009 ◽  
Vol 284 (24) ◽  
pp. 16099-16107 ◽  
Author(s):  
Mingming Pu ◽  
Xiaomin Fang ◽  
Alfred G. Redfield ◽  
Anne Gershenson ◽  
Mary F. Roberts
Keyword(s):  
Enzyme Activity ◽  
Phospholipase C ◽  
Lateral Diffusion ◽  
Lipid Vesicles ◽  
Membrane Lipid ◽  
Correlation Spectroscopy ◽  
Anionic Phospholipid ◽  
Anionic Phospholipids ◽  
Substrate Analogue ◽  
Nmr Methods

The enzymatic activity of the peripheral membrane protein, phosphatidylinositol-specific phospholipase C (PI-PLC), is increased by nonsubstrate phospholipids with the extent of enhancement tuned by the membrane lipid composition. For Bacillus thuringiensis PI-PLC, a small amount of phosphatidylcholine (PC) activates the enzyme toward its substrate PI; above 0.5 mol fraction PC (XPC), enzyme activity decreases substantially. To provide a molecular basis for this PC-dependent behavior, we used fluorescence correlation spectroscopy to explore enzyme binding to multicomponent lipid vesicles composed of PC and anionic phospholipids (that bind to the active site as substrate analogues) and high resolution field cycling 31P NMR methods to estimate internal correlation times (τc) of phospholipid headgroup motions. PI-PLC binds poorly to pure anionic phospholipid vesicles, but 0.1 XPC significantly enhances binding, increases PI-PLC activity, and slows nanosecond rotational/wobbling motions of both phospholipid headgroups, as indicated by increased τc. PI-PLC activity and phospholipid τc are constant between 0.1 and 0.5 XPC. Above this PC content, PI-PLC has little additional effect on the substrate analogue but further slows the PC τc, a motional change that correlates with the onset of reduced enzyme activity. For PC-rich bilayers, these changes, together with the reduced order parameter and enhanced lateral diffusion of the substrate analogue in the presence of PI-PLC, imply that at high XPC, kinetic inhibition of PI-PLC results from intravesicle sequestration of the enzyme from the bulk of the substrate. Both methodologies provide a detailed view of protein-lipid interactions and can be readily adapted for other peripheral membrane proteins.

Squalene synthetase. Differentiation between the two substrate binding sites by a substrate analogue

1976 ◽  
Vol 98 (7) ◽  
pp. 2018-2019 ◽  
Author(s):  
Paul R. Ortiz de Montellano ◽  
Rafael Castillo ◽  
Wayne Vinson ◽  
Jeng Shu Wei
Keyword(s):  
Binding Sites ◽  
Substrate Binding ◽  
Substrate Analogue ◽  
Substrate Binding Sites ◽  
Squalene Synthetase
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