Thermodynamic and dynamic factors involved in the stability of native protein structure in amorphous solids in relation to levels of hydration

The thermodynamic and kinetic study of the repair reactions of three damaged aliphatic amino acids (alanine, valine, and leucine) with dihydrolipoic acid (DHLA) in a polar and a nonpolar solvent is presented in this work. Two simplified protein models were explored in the most common conformations (alpha helix and beta sheet). Calculations are performed at the M06-2X-SMD/6-31++G(d,p) level of theory. DHLA has shown to be an excellent antioxidant repair agent through hydrogen-transfer reaction involving the thiol groups, with rate constants close to diffusion control in most cases. The stability of the initial protein radical is not the most important factor determining the rate of the repair reaction because stabilizing intermolecular interactions involving the protein and the antioxidant can provide additional stability to some transition states accelerating the repair of sites that would otherwise not be so quickly repaired.

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Thermodynamic bases of the stability of protein structure

Thermochimica Acta ◽

10.1016/0040-6031(90)80377-b ◽

1990 ◽

Vol 163 ◽

pp. 33-46 ◽

Cited By ~ 16

Author(s):

P.L. Privalov

Keyword(s):

Protein Structure ◽

The Stability

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In-vacuum long-wavelength macromolecular crystallography

Acta Crystallographica Section D Structural Biology ◽

10.1107/s2059798316001078 ◽

2016 ◽

Vol 72 (3) ◽

pp. 430-439 ◽

Cited By ~ 53

Author(s):

Armin Wagner ◽

Ramona Duman ◽

Keith Henderson ◽

Vitaliy Mykhaylyk

Keyword(s):

Protein Structure ◽

Diffraction Data ◽

X Rays ◽

Macromolecular Crystallography ◽

Native Protein ◽

Long Wavelength ◽

Structure Solution ◽

Dna Crystals ◽

Anomalous Signal ◽

Theoretical Considerations

Structure solution based on the weak anomalous signal from native (protein and DNA) crystals is increasingly being attempted as part of synchrotron experiments. Maximizing the measurable anomalous signal by collecting diffraction data at longer wavelengths presents a series of technical challenges caused by the increased absorption of X-rays and larger diffraction angles. A new beamline at Diamond Light Source has been built specifically for collecting data at wavelengths beyond the capability of other synchrotron macromolecular crystallography beamlines. Here, the theoretical considerations in support of the long-wavelength beamline are outlined and the in-vacuum design of the endstation is discussed, as well as other hardware features aimed at enhancing the accuracy of the diffraction data. The first commissioning results, representing the first in-vacuum protein structure solution, demonstrate the promising potential of the beamline.

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3P267 Reconstruction of native protein structure from one-dimensional information

Seibutsu Butsuri ◽

10.2142/biophys.44.s256_3 ◽

2004 ◽

Vol 44 (supplement) ◽

pp. S256

Author(s):

A.R. Kinjo ◽

K. Nishikawa

Keyword(s):

Protein Structure ◽

Native Protein ◽

One Dimensional

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Predicting absolute contact numbers of native protein structure from amino acid sequence

Proteins Structure Function and Bioinformatics ◽

10.1002/prot.20300 ◽

2004 ◽

Vol 58 (1) ◽

pp. 158-165 ◽

Cited By ~ 46

Author(s):

Akira R. Kinjo ◽

Katsuhisa Horimoto ◽

Ken Nishikawa

Keyword(s):

Protein Structure ◽

Amino Acid ◽

Amino Acid Sequence ◽

Native Protein

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Engineered Stable 5-Hydroxymethylfurfural Oxidase (HMFO) from 8BxHMFO Variant of Methylovorus sp. MP688 through B-Factor Analysis

Catalysts ◽

10.3390/catal11121503 ◽

2021 ◽

Vol 11 (12) ◽

pp. 1503

Author(s):

Qiuyang Wu ◽

Dong Lu ◽

Shuming Jin ◽

Jie Lu ◽

Fang Wang ◽

...

Keyword(s):

Factor Analysis ◽

Protein Structure ◽

Hydrogen Bonds ◽

Horseradish Peroxidase ◽

Dynamic Simulation ◽

Terephthalic Acid ◽

Biotechnological Processes ◽

The Stability ◽

Work Stability ◽

Low Activity

What is known as Furan-2,5-dicarboxylic acid (FDCA) is an attractive compound since it has similar properties to terephthalic acid. Further, 5-hydroxymethylfurfural oxidase (HMFO) is an enzyme, which could convert HMF to FDCA directly. Most wild types of HMFO have low activity on the oxidation of HMF to FDCA. The variant of 8BxHFMO from Methylovorus sp. MP688 was the only reported enzyme that was able to perform FDCA production. However, the stabilization of 8BxHMFO is still not that satisfactory, and further improvement is necessary for the industrial application of the enzyme. In this work, stability-enhanced HMFO from 8BxHFMO was engineered through employing B-factor analysis. The mutation libraries were created based on the NNK degeneracy of residues with the top ten highest B-factor value, and two of the effective mutants were screened out through the high throughput selection with the horseradish peroxidase (HRP)-Tyr assay. The mutants Q319K and N44G show a significantly increased yield of FDCA in the reaction temperature range of 30 to 40 °C. The mutant Q319K shows the best performance at 35 °C with a FDCA yield of 98% (the original 8BxHMFO was only 85%), and a half-life exceeding 72 h. Moreover, molecular dynamic simulation indicates that more hydrogen bonds are formed in the mutants, which improves the stability of the protein structure. The method could enhance the design of more stable biocatalysts; and provides potential for the further optimization and utilization of HMFO in biotechnological processes.

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Identification of native protein structures captured by principal interactions

BMC Bioinformatics ◽

10.1186/s12859-019-3186-6 ◽

2019 ◽

Vol 20 (1) ◽

Author(s):

Mehdi Mirzaie

Keyword(s):

Protein Structure ◽

Protein Structures ◽

Interaction Model ◽

Principal Component ◽

Potential Functions ◽

Native Protein ◽

Knowledge Based ◽

Total Potential ◽

Full Interaction ◽

Interaction Types

Abstract Background Evaluation of protein structure is based on trustworthy potential function. The total potential of a protein structure is approximated as the summation of all pair-wise interaction potentials. Knowledge-based potentials (KBP) are one type of potential functions derived by known experimentally determined protein structures. Although several KBP functions with different methods have been introduced, the key interactions that capture the total potential have not studied yet. Results In this study, we seek the interaction types that preserve as much of the total potential as possible. We employ a procedure based on the principal component analysis (PCA) to extract the significant and key interactions in native protein structures. We call these interactions as principal interactions and show that the results of the model that considers only these interactions are very close to the full interaction model that considers all interactions in protein fold recognition. In fact, the principal interactions maintain the discriminative power of the full interaction model. This method was evaluated on 3 KBPs with different contact definitions and thresholds of distance and revealed that their corresponding principal interactions are very similar and have a lot in common. Additionally, the principal interactions consisted of 20 % of the full interactions on average, and they are between residues, which are considered important in protein folding. Conclusions This work shows that all interaction types are not equally important in discrimination of native structure. The results of the reduced model based on principal interactions that were very close to the full interaction model suggest that a new strategy is needed to capture the role of remaining interactions (non-principal interactions) to improve the power of knowledge-based potential functions.

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