Probing the Dynamic Interface between Trimethylamine Dehydrogenase (TMADH) and Electron Transferring Flavoprotein (ETF) in the TMADH−2ETF Complex: Role of the Arg-α237 (ETF) and Tyr-442 (TMADH) Residue Pair†,‡

Biochemistry ◽  
2008 ◽  
Vol 47 (18) ◽  
pp. 5168-5181 ◽  
Author(s):  
Selena G. Burgess ◽  
Hanan Latif Messiha ◽  
Gergely Katona ◽  
Stephen E. J. Rigby ◽  
David Leys ◽  
...  
Keyword(s):  
Residue Pair ◽  
Trimethylamine Dehydrogenase ◽  
Dynamic Interface ◽  
Electron Transferring Flavoprotein

Flavin radicals, conformational sampling and robust design principles in interprotein electron transfer: the trimethylamine dehydrogenase-electron-transferring flavoprotein complex

2004 ◽  
Vol 71 ◽  
pp. 1-14
Author(s):  
David Leys ◽  
Jaswir Basran ◽  
François Talfournier ◽  
Kamaldeep K. Chohan ◽  
Andrew W. Munro ◽  
...  
Keyword(s):  
Electron Transfer ◽  
Dimensional Space ◽  
Three Dimensional ◽  
Kinetic Studies ◽  
Molecular Assembly ◽  
Conformational Sampling ◽  
Trimethylamine Dehydrogenase ◽  
Key Residues ◽  
Electron Transferring Flavoprotein ◽  
Electron Transfer Complex

TMADH (trimethylamine dehydrogenase) is a complex iron-sulphur flavoprotein that forms a soluble electron-transfer complex with ETF (electron-transferring flavoprotein). The mechanism of electron transfer between TMADH and ETF has been studied using stopped-flow kinetic and mutagenesis methods, and more recently by X-ray crystallography. Potentiometric methods have also been used to identify key residues involved in the stabilization of the flavin radical semiquinone species in ETF. These studies have demonstrated a key role for 'conformational sampling' in the electron-transfer complex, facilitated by two-site contact of ETF with TMADH. Exploration of three-dimensional space in the complex allows the FAD of ETF to find conformations compatible with enhanced electronic coupling with the 4Fe-4S centre of TMADH. This mechanism of electron transfer provides for a more robust and accessible design principle for interprotein electron transfer compared with simpler models that invoke the collision of redox partners followed by electron transfer. The structure of the TMADH-ETF complex confirms the role of key residues in electron transfer and molecular assembly, originally suggested from detailed kinetic studies in wild-type and mutant complexes, and from molecular modelling.

scholarly journals The Dynamic Interface Between the Bone Marrow Vascular Niche and Hematopoietic Stem Cells in Myeloid Malignancy

2021 ◽  
Vol 9 ◽  
Author(s):  
Laura Mosteo ◽  
Joanna Storer ◽  
Kiran Batta ◽  
Emma J. Searle ◽  
Delfim Duarte ◽  
...  
Keyword(s):  
Stem Cells ◽  
Bone Marrow ◽  
Hematopoietic Stem Cells ◽  
Hematopoietic Stem ◽  
Vascular Niche ◽  
Dynamic Interface ◽  
Bone Marrow Vascular Niche ◽  
Bidirectional Interactions ◽  
Vascular Compartment

Hematopoietic stem cells interact with bone marrow niches, including highly specialized blood vessels. Recent studies have revealed the phenotypic and functional heterogeneity of bone marrow endothelial cells. This has facilitated the analysis of the vascular microenvironment in steady state and malignant hematopoiesis. In this review, we provide an overview of the bone marrow microenvironment, focusing on refined analyses of the marrow vascular compartment performed in mouse studies. We also discuss the emerging role of the vascular niche in “inflamm-aging” and clonal hematopoiesis, and how the endothelial microenvironment influences, supports and interacts with hematopoietic cells in acute myeloid leukemia and myelodysplastic syndromes, as exemplar states of malignant myelopoiesis. Finally, we provide an overview of strategies for modulating these bidirectional interactions to therapeutic effect in myeloid malignancies.

Polycentric Stakeholder Analysis

2019 ◽  
pp. 189-208
Author(s):  
Paul Dragos Aligica ◽  
Peter J. Boettke ◽  
Vlad Tarko
Keyword(s):  
Corporate Social Responsibility ◽  
Social Responsibility ◽  
Stakeholder Analysis ◽  
The Public ◽  
Public Role ◽  
Governance Systems ◽  
Dynamic Interface ◽  
Corporate Social ◽  
Sensitive Issues

Chapter 9 pushes further the frontier of the discussion into a new, growing and controversial governance debate area: that of corporate social responsibility. One of the most sensitive issues in polycentric governance systems, with their hybrid institutional arrangements at the dynamic interface between the “public” and the “private,” is to specify what are—and what are not—the responsibilities of the private sector—business firms and enterprises—when it comes to the public domain. This chapter offers an exploratory attempt to address this challenge. Corporate social responsibility (CSR) has emerged in the last several decades as a preeminent concept and issue area engaging the problem of public role of private business. This chapter demonstrates how the ideas and theories discussed so far combine, complement, and bolster this literature and the applied-level insights based on it.

scholarly journals Electron Transfer and Conformational Change in Complexes of Trimethylamine Dehydrogenase and Electron Transferring Flavoprotein

2001 ◽  
Vol 277 (10) ◽  
pp. 8457-8465 ◽  
Author(s):  
Matthew Jones ◽  
Francois Talfournier ◽  
Anton Bobrov ◽  
J. Günter Grossmann ◽  
Nikolai Vekshin ◽  
...  
Keyword(s):  
Electron Transfer ◽  
Conformational Change ◽  
Trimethylamine Dehydrogenase ◽  
Electron Transferring Flavoprotein
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