scholarly journals Role of long-range aromatic clique and community in protein stability

2018 ◽  
Author(s):  
P Mahanta ◽  
A Bhardwaj ◽  
VS Reddy ◽  
S Ramakumar

AbstractAromatic interactions make an important contribution to protein structure, function, folding and have attracted intense study. Earlier studies on a recombinant xylanase from Bacillus sp. NG-27 (RBSX), which has the ubiquitous (beta/alpha)8-triosephosphate isomerase barrel fold showed that three aromatic residues to alanine substitutions, in the N-terminal and C-terminal regions, significantly decreased the stability of the enzyme. Of these mutations, F4A mutation decreased the stability of the enzyme by ∼4 degree C, whereas W6A mutation and Y343A mutation remarkably decreased the stability of the enzyme by ∼10 degree C. On the other hand, the F4W mutation did not affect the thermal stability of RBSX. We provide here a network perspective of aromatic-aromatic interactions in terms of aromatic clique community and long-range association. Our study reveals that disruption of long-range k-clique aromatic interaction cluster holding the N- and C-terminal regions are associated with the decreased stability of the enzyme. The present work reiterates as well as expands on those findings concerning the role of interactions between the N- and C-terminus in protein stability. Furthermore, comparative analyses of crystal structures of homologous pairs of proteins from thermophilic and mesophilic organisms emphasize the prevalence of long-range k-clique communities of aromatic interaction that may be playing an important role and highlights an additional source of stability in thermophilic proteins. The design principle based on clustering of long-range aromatic residues in the form of aromatic-clique and clique community may be effectively applied to enhance the stability of enzymes for biotechnological applications.DatabaseThe coordinates o fF4A, F4W, W6A, and Y343A are deposited in the PDB database under the accession numbers 5EFF, 5E58, 5EFD, and 5EBA respectively.AbbreviationsBSX, xylanase from Bacilllus sp. NG-27; RBSX, recombinant BSX xylanase; TIM, Triosephosphate isomerase; GH10, Glycosyl hydrolase family 10; 3D, three-dimensional; r.m.s.d, root mean square deviation; RSA, relative solvent accessible surface area; Tm, melting temperature; CD, Circular Dichroism; BHX, GH10 xylanase from Bacillus halodurans; BFX, GH10 xylanase from Bacillus firmus; TmxB, GH10 xylanase from Thermotoga maritima

Medicina ◽  
2018 ◽  
Vol 54 (3) ◽  
pp. 39
Author(s):  
Wei Li ◽  
Bi-De Liu ◽  
Kai Liao ◽  
Yong Liu ◽  
Zi-Jin Wan ◽  
...  

Background and Objective: Although triptolide was effective for prostate cancer (PCa), the mechanism is still unclear. Androgen receptor (AR) plays a large role in the development and progression of PCa, even after castration. The present study aimed at investigating the effects of triptolide on AR protein stability and the possible mechanism. Materials and Methods: By blocking protein synthesis with cycloheximide (CHX), the effect of triptolide on AR protein stability was investigated with western blot assay. The potential role of calpains in triptolide reduced AR protein stability was investigated with calpain inhibitor and Ca2+ chelator. Results: Triptolide down-regulated AR protein level when protein synthesis was blocked by CHX, demonstrating the decrease of AR protein stability. The AR protein level was restored when the cells were co-treated with triptolide and calpain inhibitor or Ca2+ chelator, indicating the important role of calpains. Conclusions: The results indicate that triptolide can activate calpain via promoting intracellular Ca2+ accumulation, and thus decrease the stability of AR protein, subsequently resulting in the breakdown of the AR protein in LNCaP cells. This work provides an experimental basis and evidence to elucidate the anti-PCa mechanisms of triptolide.


1962 ◽  
Vol 40 (1) ◽  
pp. 1287-1298 ◽  
Author(s):  
L. Salem

The various long-range forces which are effective between molecules in their electronic ground states are examined. Orders of magnitude are given for those forces which should occur in the interaction of lipide and protein chains. It is found that electrostatic forces should be responsible for bringing and holding together protein and lipide components, but London – Van der Waals dispersion forces are probably of paramount importance in maintaining the lipide chains together in micelles or double layers.Special attention is drawn to the dispersion forces and to the conditions under which these forces are locally additive; one can calculate accurate values of the dispersion energy of interaction between saturated hydrocarbon chains at short distances (a few angstroms apart) by adding all the bond–bond interactions. A general expression is given for the dispersion energy between two parallel and opposed chains built out of identical units, and numerical values are given for the case of closely packed hydrocarbon chains.The total attraction energy is extremely sensitive to the intermolecular distance. The role of this "distance-specificity" in interactions involving unsaturated fatty acid chains and its contribution to the stability of lipoproteins is briefly examined.


1962 ◽  
Vol 40 (9) ◽  
pp. 1287-1298 ◽  
Author(s):  
L. Salem

The various long-range forces which are effective between molecules in their electronic ground states are examined. Orders of magnitude are given for those forces which should occur in the interaction of lipide and protein chains. It is found that electrostatic forces should be responsible for bringing and holding together protein and lipide components, but London – Van der Waals dispersion forces are probably of paramount importance in maintaining the lipide chains together in micelles or double layers.Special attention is drawn to the dispersion forces and to the conditions under which these forces are locally additive; one can calculate accurate values of the dispersion energy of interaction between saturated hydrocarbon chains at short distances (a few angstroms apart) by adding all the bond–bond interactions. A general expression is given for the dispersion energy between two parallel and opposed chains built out of identical units, and numerical values are given for the case of closely packed hydrocarbon chains.The total attraction energy is extremely sensitive to the intermolecular distance. The role of this "distance-specificity" in interactions involving unsaturated fatty acid chains and its contribution to the stability of lipoproteins is briefly examined.


Observations of phenol-benzene and ammonia—benzene complexes in the gas phase show that hydrogen bonds link their proton donors to the π electrons of the benzene with a bond energy of between 2 and 4 kcal mol -1 , large enough to be biologically significant. Intramolecular hydrogen bonds between OH and NH donors and aromatic acceptors have also been found in crystal structures of organic compounds. NH-aromatic interactions stabilize x-helices if donors and acceptors occur at successive turns of the helix. These interactions also contribute to the stability of several proteins and play an important part in cellular and synaptic signal transmission.


Author(s):  
Marie-Pierre Valignat ◽  
Francois Vandenbrouck ◽  
Anne-Marie Cazabat
Keyword(s):  

2013 ◽  
pp. 97-116 ◽  
Author(s):  
A. Apokin

The author compares several quantitative and qualitative approaches to forecasting to find appropriate methods to incorporate technological change in long-range forecasts of the world economy. A?number of long-run forecasts (with horizons over 10 years) for the world economy and national economies is reviewed to outline advantages and drawbacks for different ways to account for technological change. Various approaches based on their sensitivity to data quality and robustness to model misspecifications are compared and recommendations are offered on the choice of appropriate technique in long-run forecasts of the world economy in the presence of technological change.


TAPPI Journal ◽  
2009 ◽  
Vol 8 (1) ◽  
pp. 20-26 ◽  
Author(s):  
PEEYUSH TRIPATHI ◽  
MARGARET JOYCE ◽  
PAUL D. FLEMING ◽  
MASAHIRO SUGIHARA

Using an experimental design approach, researchers altered process parameters and material prop-erties to stabilize the curtain of a pilot curtain coater at high speeds. Part I of this paper identifies the four significant variables that influence curtain stability. The boundary layer air removal system was critical to the stability of the curtain and base sheet roughness was found to be very important. A shear thinning coating rheology and higher curtain heights improved the curtain stability at high speeds. The sizing of the base sheet affected coverage and cur-tain stability because of its effect on base sheet wettability. The role of surfactant was inconclusive. Part II of this paper will report on further optimization of curtain stability with these four variables using a D-optimal partial-facto-rial design.


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