scholarly journals The Folding Energy Landscape of the Dimerization Domain of Escherichia coli Trp Repressor: A Joint Experimental and Theoretical Investigation

2006 ◽  
Vol 363 (1) ◽  
pp. 262-278 ◽  
Author(s):  
B. Robert Simler ◽  
Yaakov Levy ◽  
José N. Onuchic ◽  
C. Robert Matthews
Keyword(s):  
Escherichia Coli ◽  
Theoretical Investigation ◽  
Energy Landscape ◽  
Folding Energy ◽  
Dimerization Domain ◽  
Trp Repressor

scholarly journals Analysis of heterodimer formation by the Escherichia coli trp repressor

1993 ◽  
Vol 268 (20) ◽  
pp. 14794-14798
Author(s):  
B.K. Hurlburt ◽  
C. Yanofsky
Keyword(s):  
Escherichia Coli ◽  
Trp Repressor

scholarly journals Intracellular Trp repressor levels in Escherichia coli.

1986 ◽  
Vol 167 (1) ◽  
pp. 272-278 ◽  
Author(s):  
R P Gunsalus ◽  
A G Miguel ◽  
G L Gunsalus
Keyword(s):  
Escherichia Coli ◽  
Trp Repressor

scholarly journals Computational Protein Stabilization Can Affect Folding Energy Landscapes and Lead to Domain-Swapped Dimers

2021 ◽  
Author(s):  
Klara Markova ◽  
Antonin Kunka ◽  
Klaudia Chmelova ◽  
Martin Havlasek ◽  
Petra Babkova ◽  
...  
Keyword(s):  
Protein Folding ◽  
Protein Design ◽  
Energy Landscape ◽  
Single Point ◽  
Three Dimensional ◽  
Protein Stabilization ◽  
Dimensional Structure ◽  
Evolutionary Analysis ◽  
Folding Energy

<p>The functionality of a protein depends on its unique three-dimensional structure, which is a result of the folding process when the nascent polypeptide follows a funnel-like energy landscape to reach a global energy minimum. Computer-encoded algorithms are increasingly employed to stabilize native proteins for use in research and biotechnology applications. Here, we reveal a unique example where the computational stabilization of a monomeric α/β-hydrolase enzyme (<i>T</i><sub>m</sub> = 73.5°C; Δ<i>T</i><sub>m</sub> > 23°C) affected the protein folding energy landscape. Introduction of eleven single-point stabilizing mutations based on force field calculations and evolutionary analysis yielded catalytically active domain-swapped intermediates trapped in local energy minima. Crystallographic structures revealed that these stabilizing mutations target cryptic hinge regions and newly introduced secondary interfaces, where they make extensive non-covalent interactions between the intertwined misfolded protomers. The existence of domain-swapped dimers in a solution is further confirmed experimentally by data obtained from SAXS and crosslinking mass spectrometry. Unfolding experiments showed that the domain-swapped dimers can be irreversibly converted into native-like monomers, suggesting that the domain-swapping occurs exclusively <i>in vivo</i>. Our findings uncovered hidden protein-folding consequences of computational protein design, which need to be taken into account when applying a rational stabilization to proteins of biological and pharmaceutical interest.</p>

scholarly journals Computational Protein Stabilization Can Affect Folding Energy Landscapes and Lead to Domain-Swapped Dimers

2021 ◽  
Author(s):  
Klara Markova ◽  
Antonin Kunka ◽  
Klaudia Chmelova ◽  
Martin Havlasek ◽  
Petra Babkova ◽  
...  
Keyword(s):  
Protein Folding ◽  
Protein Design ◽  
Energy Landscape ◽  
Single Point ◽  
Three Dimensional ◽  
Protein Stabilization ◽  
Dimensional Structure ◽  
Evolutionary Analysis ◽  
Folding Energy

<p>The functionality of a protein depends on its unique three-dimensional structure, which is a result of the folding process when the nascent polypeptide follows a funnel-like energy landscape to reach a global energy minimum. Computer-encoded algorithms are increasingly employed to stabilize native proteins for use in research and biotechnology applications. Here, we reveal a unique example where the computational stabilization of a monomeric α/β-hydrolase enzyme (<i>T</i><sub>m</sub> = 73.5°C; Δ<i>T</i><sub>m</sub> > 23°C) affected the protein folding energy landscape. Introduction of eleven single-point stabilizing mutations based on force field calculations and evolutionary analysis yielded catalytically active domain-swapped intermediates trapped in local energy minima. Crystallographic structures revealed that these stabilizing mutations target cryptic hinge regions and newly introduced secondary interfaces, where they make extensive non-covalent interactions between the intertwined misfolded protomers. The existence of domain-swapped dimers in a solution is further confirmed experimentally by data obtained from SAXS and crosslinking mass spectrometry. Unfolding experiments showed that the domain-swapped dimers can be irreversibly converted into native-like monomers, suggesting that the domain-swapping occurs exclusively <i>in vivo</i>. Our findings uncovered hidden protein-folding consequences of computational protein design, which need to be taken into account when applying a rational stabilization to proteins of biological and pharmaceutical interest.</p>

Modulation of the Folding Energy Landscape of Cytochromecwith Salt

2004 ◽  
Vol 126 (43) ◽  
pp. 13934-13935 ◽  
Author(s):  
Shi Zhong ◽  
Denis L. Rousseau ◽  
Syun-Ru Yeh
Keyword(s):  
Energy Landscape ◽  
Folding Energy

scholarly journals RNA Pseudoknot Folding Energy Landscape Elucidated with T-Jump Measurements and Kinetic Modeling

2015 ◽  
Vol 108 (2) ◽  
pp. 236a ◽  
Author(s):  
Jorjethe Roca ◽  
Yogambigai Velmurugu ◽  
Ranjani Narayanan ◽  
Prasanth Narayanan ◽  
Serguei Kouznetsov ◽  
...  
Keyword(s):  
Kinetic Modeling ◽  
Energy Landscape ◽  
Folding Energy ◽  
Rna Pseudoknot
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