Enhanced dynamics of conformationally heterogeneous T7 bacteriophage lysozyme native state attenuates its stability and activity

2019 ◽  
Vol 476 (3) ◽  
pp. 613-628 ◽  
Author(s):  
Meenakshi Sharma ◽  
Nancy Jaiswal ◽  
Dinesh Kumar ◽  
Krishna Mohan Poluri
Keyword(s):  
Dynamic Properties ◽  
Nmr Relaxation ◽  
Dynamic Features ◽  
Native State ◽  
Structure Dynamics ◽  
Functional Dynamics ◽  
State Ensemble ◽  
The Stability ◽  
Ph Range ◽  
Relationship Of

Abstract Proteins are dynamic in nature and exist in a set of equilibrium conformations on various timescale motions. The flexibility of proteins governs various biological functions, and therefore elucidation of such functional dynamics is essential. In this context, we have studied the structure–dynamics–stability–activity relationship of bacteriophage T7 lysozyme/endolysin (T7L) native-state ensemble in the pH range of 6–8. Our studies established that T7L native state is conformationally heterogeneous, as several residues of its C-terminal half are present in two conformations (major and minor) in the slow exchange time scale of nuclear magnetic resonance (NMR). Structural and dynamic studies suggested that the residues belonging to minor conformations do exhibit native-like structural and dynamic features. Furthermore, the NMR relaxation experiments unraveled that the native state is highly dynamic and the dynamic behavior is regulated by the pH, as the pH 6 conformation exhibited enhanced dynamics compared with pH 7 and 8. The stability measurements and cell-based activity studies on T7L indicated that the native protein at pH 6 is ∼2 kcal less stable and is ∼50% less active than those of pH 7 and 8. A comprehensive analysis of the T7L active site, unfolding initiation sites and the residues with altered dynamics outlined that the attenuation of stability and activity is a resultant of its enhanced dynamic properties, which, in turn, can be attributed to the protonation/deprotonation of its partially buried His residues. Our study on T7L structure–dynamics–activity paradigm could assist in engineering novel amidase-based endolysins with enhanced activity and stability over a broad pH range.

Double mutant of chymotrypsin inhibitor 2 stabilized through increased conformational entropy

2021 ◽  
Author(s):  
Yulian Gavrilov ◽  
Felix Kümmerer ◽  
Simone Orioli ◽  
Andreas Prestel ◽  
Kresten Lindorff-Larsen ◽  
...  
Keyword(s):  
Double Mutant ◽  
Conformational Dynamics ◽  
Nmr Relaxation ◽  
Conformational Heterogeneity ◽  
Native State ◽  
Chymotrypsin Inhibitor 2 ◽  
Relaxation Measurements ◽  
The Stability ◽  
Dynamics Simulations ◽  
Mutant Forms

The conformational heterogeneity of a folded protein can affect both its function but also stability and folding. We recently discovered and characterized a stabilized double mutant (L49I/I57V) of the protein CI2 and showed that state-of-the-art prediction methods could not predict the increased stability relative to the wild-type protein. Here we have examined whether changed native state dynamics, and resulting entropy changes, can explain the stability changes in the double mutant protein, as well as the two single mutant forms. We have combined NMR relaxation measurements of the ps-ns dynamics of amide groups in the backbone and the methyl groups in the side-chains with molecular dynamics simulations to quantify the native state dynamics. The NMR experiments reveal that the mutations have different effects on the conformational flexibility of CI2: A reduction in conformational dynamics (and entropy) of the native state of L49I variant correlates with its decreased stability, while increased dynamics of the I57V and L49I/I57V variants correlates with their increased stability. These findings suggest that explicitly accounting for changes in native state entropy might be needed to improve the predictions of the effect of mutations on protein stability.

Solution Structure, Dynamics, and Thermodynamics of the Native State Ensemble of the Sem-5 C-Terminal SH3 Domain†

Biochemistry ◽  
2003 ◽  
Vol 42 (19) ◽  
pp. 5582-5591 ◽  
Author(s):  
Josephine C. Ferreon ◽  
David E. Volk ◽  
Bruce A. Luxon ◽  
David G. Gorenstein ◽  
Vincent J. Hilser
Keyword(s):  
Solution Structure ◽  
Sh3 Domain ◽  
Native State ◽  
Structure Dynamics ◽  
State Ensemble

A FORECAST OF PRODUCTIVE LONGEVITY OF HOLSTEIN COWS BY INDIRECT SIGNS

2020 ◽  
Author(s):  
З.С. САНОВА
Keyword(s):  
Correlation Coefficient ◽  
Aging Process ◽  
Direct Relationship ◽  
Stability Index ◽  
Age At First Calving ◽  
Group I ◽  
Predicted Values ◽  
The Stability ◽  
Relationship Of ◽  
The Relationship

В статье представлены материалы о взаимосвязи продолжительности продуктивного использования коров с характеристикой устойчивости к деградации, с возрастом отела и удоем. В исследованной, разнородной по происхождению, группе животных для прогноза продуктивного периода коров, обусловленного устойчивостью к деградации и возрастом первого отела, пригодно уравнение регрессии, аргументами в котором являются индекс устойчивости, возраст первого отела в первой и второй степенях. Коэффициент корреляции межу предсказанными значениями продуктивного периода и его фактическими величинами в I группе составляет 0,502, во II - 0,604. При этом крайние варианты прогнозируются со статистическими ошибками 5 мес при оценке индекса устойчивости по 2 лактациям и 4,1 мес по 3, а средние варианты, соответственно, 1,6 и 1,51 мес. Индекс устойчивости к процессу старения является важной характеристикой биологических особенностей коров, определяющий их продуктивное долголетие. Его оценка по первым 2 и 3 лактациям имеет прямолинейную связь с продуктивным периодом (r=0,4109 и r=0,5270), соответственно. Зависимость продуктивного периода от возраста первого отела криволинейная — с увеличением возраста первого отела сокращается срок продуктивного использования, при возрасте первого отела более 1400 дней срок продуктивного использования колеблется от 1,33 до 1,41 лактации. Коэффициент корреляции между этими характеристиками коров составляет - 0,2164 в I и - 0,2620 во II группах. The article presents materials about the relationship of the duration of productive use of cows with the characteristic of resistance to degradation, with the age of calving and milk yield. In the studied group of animals, which is heterogeneous in origin, the regression equation is suitable for predicting the productive period of cows due to resistance to degradation and the age of the first calving, the arguments of which are the stability index, the age of the first calving in the first and second degrees. The correlation coefficient between the predicted values of the productive period and its actual values in group I is 0.502, in group II - 0.604. At the same time, the extreme variants are predicted with statistical errors of 5 months when evaluating the stability index for 2 lactations and 4.1 months for 3, and the average variants, respectively, are 1.6 and 1.51 months. The index of resistance to the aging process is an important characteristic of the biological characteristics of cows, which determines their productive longevity. Its estimate for the first 2 and 3 lactations has a direct relationship with the productive period (r=0.4109 and r=0.5270), respectively. The dependence of the productive period age at first calving curvilinear with increasing age at first calving reduces the time to productive use, while age at first calving of more than 1400 days, the period of productive use ranges from 1.33 to 1.41 lactation. The correlation coefficient between these characteristics of cows is-0.2164 in I and-0.2620 in II groups.

DEVELOPMENT OF THE BASIC CRITERIA FOR RUSSIAN COASTS TYPIFICATION

2017 ◽  
Author(s):  
Рубен Косян ◽  
Ruben Kosyan ◽  
Viacheslav Krylenko ◽  
Viacheslav Krylenko
Keyword(s):  
Coastal Zone ◽  
Coastal Area ◽  
Economic Activity ◽  
Basic Information ◽  
Dynamic Features ◽  
Static State ◽  
Evolutionary Features ◽  
Coastal Features ◽  
The Stability

There are many types of coasts classifications that indicate main coastal features. As a rule, the "static" state of the coasts is considered regardless of their evolutionary features and ways to further transformation. Since the most part of the coastal zone studies aimed at ensuring of economic activity, it is clear that the classification of coast types should indicate total information required by the users. Accordingly, the coast classification should include the criterion, characterizing as dynamic features of the coast and the conditions and opportunities of economic activity. The coast classification, of course, should be based on geomorphological coast typification. Similar typification has been developed by leading scientists from Russia and can be used with minimal modifications. The authors propose to add to basic information (geomorphological type of coast) the evaluative part for each coast sector. It will include the estimation of the coast changes probability and the complexity of the coast stabilization for economic activity. This method will allow to assess the dynamics of specific coastal sections and the processes intensity and, as a result – the stability of the coastal area.

A simulation apparatus for the experimental study of batch reactor control methods

1986 ◽  
Vol 51 (6) ◽  
pp. 1259-1267
Author(s):  
Josef Horák ◽  
Petr Beránek
Keyword(s):  
Experimental Study ◽  
Closed Loop ◽  
Dynamic Properties ◽  
Batch Reactor ◽  
Exothermic Reaction ◽  
Electric Heating ◽  
Batch Reactors ◽  
Exchange Area ◽  
The Stability ◽  
Methods Of Control

A simulation apparatus for the experimental study of the methods of control of batch reactors is devised. In this apparatus, the production of heat by an exothermic reaction is replaced by electric heating controlled by a computer in a closed loop; the reactor is cooled with an external cooler whose dynamic properties can be varied while keeping the heat exchange area constant. The effect of the cooler geometry on its dynamic properties is investigated and the effect of the cooler inertia on the stability and safety of the on-off temperature control in the unstable pseudostationary state is examined.

Schiff base equilibria. II. Beryllium complexes of N-n-butylsalicylideneimine and the hydrolysis of the Be2+ ion

1965 ◽  
Vol 18 (5) ◽  
pp. 651 ◽  
Author(s):  
RW Green ◽  
PW Alexander
Keyword(s):  
Aqueous Solution ◽  
Schiff Base ◽  
Complex Formation ◽  
Distribution Coefficient ◽  
Dilute Aqueous Solution ◽  
The Stability ◽  
Ph Range ◽  
Hydrolysis Of ◽  
Beryllium Complexes ◽  
Equilibria In Aqueous Solution

The Schiff base, N-n-butylsalicylideneimine, extracts more than 99.8% beryllium into toluene from dilute aqueous solution. The distribution of beryllium has been studied in the pH range 5-13 and is discussed in terms of the several complex equilibria in aqueous solution. The stability constants of the complexes formed between beryllium and the Schiff base are log β1 11.1 and log β2 20.4, and the distribution coefficient of the bis complex is 550. Over most of the pH range, hydrolysis of the Be2+ ion competes with complex formation and provides a means of measuring the hydrolysis constants. They are for the reactions: Be(H2O)42+ ↔ 2H+ + Be(H2O)2(OH)2, log*β2 - 13.65; Be(H2O)42+ ↔ 3H+ + Be(H2O)(OH)3-, log*β3 -24.11.

scholarly journals Investigations of ternary complexes of Co(II) and Ni(II) with thiodiacetate anion and 1,10-phenanthroline or 2,2’-bipyridine in aqueous solutions

2014 ◽  
Vol 13 (1) ◽  
Author(s):  
Dariusz Wyrzykowski ◽  
Joanna Pranczk ◽  
Dagmara Jacewicz ◽  
Aleksandra Tesmar ◽  
Bogusław Pilarski ◽  
...  
Keyword(s):  
Aqueous Solutions ◽  
Substitution Reactions ◽  
Experimental Conditions ◽  
Kinetic Measurements ◽  
Hydroxo Complexes ◽  
Binary Complexes ◽  
Vis Spectroscopy ◽  
Potentiometric Titration Method ◽  
The Stability ◽  
Ph Range

AbstractA potentiometric titration method (PT) and a stopped-flow kinetic technique monitored by a UV−Vis spectroscopy have been used to characterize the stability of series of Co(II)- and Ni(II)-thiodiacetato complexes, M(TDA), in the presence of 1,10-phenanthroline (phen) or 2,2’-bipyridine (bipy) in aqueous solutions. The stability constants of the binary (1:1), ternary (1:1:1) as well as the resulting hydroxo complexes were evaluated and compared to the corresponding oxydiacetate complexes. Based on the species distribution as a function of pH the relative predominance of the species in the system over a pH range was discussed. Furthermore, the kinetic measurements of the substitution reactions of the aqua ligands to phen or bipy in the coordination sphere of the binary complexes M(TDA) were performed in the 288–303 K temperature range, at a constant concentration of phen or bipy and at seven different concentrations of the binary complexes (0.2–0.5 mM). The kinetic stability of the M(TDA) complexes was discussed in relation to the experimental conditions and the kind of the auxiliary ligands (phen/bipy). Moreover, the influence of the type of primary ligand (thiodiacetate/oxydiacetate) on the substitution rate of the auxiliary ligands was also compared.

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