Crystal structure of adenylate kinase from an extremophilic archaeon Aeropyrum pernix with ATP and AMP

2020 ◽  
Vol 168 (3) ◽  
pp. 223-229
Author(s):  
Yoshinori Shibanuma ◽  
Naoki Nemoto ◽  
Norifumi Yamamoto ◽  
Gen-Ichi Sampei ◽  
Gota Kawai
Keyword(s):  
Crystal Structure ◽  
Molecular Dynamics ◽  
Quantum Mechanics ◽  
Reaction Mechanism ◽  
Adenylate Kinase ◽  
Reaction Coordinate ◽  
Amino Acid Residues ◽  
Aeropyrum Pernix ◽  
Adenylate Kinases

Abstract The crystal structure of an adenylate kinase from an extremophilic archaeon Aeropyrum pernix was determined in complex with full ligands, ATP-Mg2+ and AMP, at a resolution of 2.0 Å. The protein forms a trimer as found for other adenylate kinases from archaea. Interestingly, the reacting three atoms, two phosphorus and one oxygen atoms, were located almost in line, supporting the SN2 nucleophilic substitution reaction mechanism. Based on the crystal structure obtained, the reaction coordinate was estimated by the quantum mechanics calculations combined with molecular dynamics. It was found that the reaction undergoes two energy barriers; the steps for breaking the bond between the oxygen and γ-phosphorus atoms of ATP to produce a phosphoryl fragment and creating the bond between the phosphoryl fragment and the oxygen atom of the β-phosphate group of ADP. The reaction coordinate analysis also suggested the role of amino-acid residues for the catalysis of adenylate kinase.

scholarly journals Molecular Dynamics Simulations of a Cytochrome P450 from Tepidiphilus thermophilus (P450-TT) Reveal How Its Substrate-Binding Channel Opens

Molecules ◽  
2021 ◽  
Vol 26 (12) ◽  
pp. 3614
Author(s):  
Abayomi S. Faponle ◽  
Anupom Roy ◽  
Ayodeji A. Adelegan ◽  
James W. Gauld
Keyword(s):  
Crystal Structure ◽  
Molecular Dynamics ◽  
Cytochrome P450 ◽  
Amino Acid ◽  
Molecular Dynamics Simulations ◽  
Organic Molecules ◽  
Side Chain ◽  
Relative Solvent Accessibility ◽  
Amino Acid Residues ◽  
Dynamics Simulations

Cytochrome P450s (P450) are important enzymes in biology with useful biochemical reactions in, for instance, drug and xenobiotics metabolisms, biotechnology, and health. Recently, the crystal structure of a new member of the CYP116B family has been resolved. This enzyme is a cytochrome P450 (CYP116B46) from Tepidiphilus thermophilus (P450-TT) and has potential for the oxy-functionalization of organic molecules such as fatty acids, terpenes, steroids, and statins. However, it was thought that the opening to its hitherto identified substrate channel was too small to allow organic molecules to enter. To investigate this, we performed molecular dynamics simulations on the enzyme. The results suggest that the crystal structure is not relaxed, possibly due to crystal packing effects, and that its tunnel structure is constrained. In addition, the simulations revealed two key amino acid residues at the mouth of the channel; a glutamyl and an arginyl. The glutamyl’s side chain tightens and relaxes the opening to the channel in conjunction with the arginyl’s, though the latter’s side chain is less dramatically changed after the initial relaxation of its conformations. Additionally, it was observed that the effect of increased temperature did not considerably affect the dynamics of the enzyme fold, including the relative solvent accessibility of the amino acid residues that make up the substrate channel wall even as compared to the changes that occurred at room temperature. Interestingly, the substrate channel became distinguishable as a prominent tunnel that is likely to accommodate small- to medium-sized organic molecules for bioconversions. That is, P450-TT has the ability to pass appropriate organic substrates to its active site through its elaborate substrate channel, and notably, is able to control or gate any molecules at the opening to this channel.

Deterministic role of structural flexibility on catalytic activity of conductive 2D layered metal–organic frameworks

2021 ◽  
Author(s):  
Mohammad R. Momeni ◽  
Zeyu Zhang ◽  
Farnaz A. Shakib
Keyword(s):  
Molecular Dynamics ◽  
Quantum Mechanics ◽  
Catalytic Activity ◽  
Metal Organic Frameworks ◽  
Structural Flexibility ◽  
Classical Molecular Dynamics ◽  
Structural Deformations ◽  
Metal Organic

A combined quantum mechanics and classical molecular dynamics approach is used to unravel the effects of structural deformations and heterogeneity on catalytic activity of 2D π-stacked layered metal–organic frameworks.

Using Data Mining Techniques to Probe the Role of Hydrophobic Residues in Protein Folding and Unfolding Simulations

2010 ◽  
pp. 258-276
Author(s):  
Cândida G. Silva ◽  
Pedro Gabriel Ferreira ◽  
Paulo J. Azevedo ◽  
Rui M.M. Brito
Keyword(s):  
Data Mining ◽  
Molecular Dynamics ◽  
Protein Folding ◽  
Protein Unfolding ◽  
Amino Acid Residues ◽  
Molecular Events ◽  
Accessible Surface ◽  
Using Data ◽  
Dynamics Simulations

The protein folding problem, i.e. the identification of the rules that determine the acquisition of the native, functional, three-dimensional structure of a protein from its linear sequence of amino-acids, still is a major challenge in structural molecular biology. Moreover, the identification of a series of neurodegenerative diseases as protein unfolding/misfolding disorders highlights the importance of a detailed characterisation of the molecular events driving the unfolding and misfolding processes in proteins. One way of exploring these processes is through the use of molecular dynamics simulations. The analysis and comparison of the enormous amount of data generated by multiple protein folding or unfolding simulations is not a trivial task, presenting many interesting challenges to the data mining community. Considering the central role of the hydrophobic effect in protein folding, we show here the application of two data mining methods – hierarchical clustering and association rules – for the analysis and comparison of the solvent accessible surface area (SASA) variation profiles of each one of the 127 amino-acid residues in the amyloidogenic protein Transthyretin, across multiple molecular dynamics protein unfolding simulations.

scholarly journals Temporary Intermediates of L-Trp Along the Reaction Pathway of Human Indoleamine 2,3-Dioxygenase 1 and Identification of an Exo Site

2021 ◽  
Vol 14 ◽  
pp. 117864692110529
Author(s):  
Manon Mirgaux ◽  
Laurence Leherte ◽  
Johan Wouters
Keyword(s):  
Molecular Dynamics ◽  
Reaction Mechanism ◽  
Crystal Structures ◽  
Protein Dynamics ◽  
Active Site ◽  
Reaction Pathway ◽  
Small Unit ◽  
Indoleamine 2,3 Dioxygenase ◽  
Dynamics Simulations

Protein dynamics governs most of the fundamental processes in the human body. Particularly, the dynamics of loops located near an active site can be involved in the positioning of the substrate and the reaction mechanism. The understanding of the functioning of dynamic loops is therefore a challenge, and often requires the use of a multi-disciplinary approach mixing, for example, crystallographic experiments and molecular dynamics simulations. In the present work, the dynamic behavior of the JK-loop of the human indoleamine 2,3-dioxygenase 1 hemoprotein, a target for immunotherapy, is investigated. To overcome the lack of knowledge on this dynamism, the study reported here is based on 3 crystal structures presenting different conformations of the loop, completed with molecular dynamics trajectories and MM-GBSA analyses, in order to trace the reaction pathway of the enzyme. In addition, the crystal structures identify an exo site in the small unit of the enzyme, that is populated redundantly by the substrate or the product of the reaction. The role of this newer reported exo site still needs to be investigated.

scholarly journals The role of the first transmembrane helix in bacterial YidC: Insights from the crystal structure and molecular dynamics simulations

2021 ◽  
Author(s):  
Xiaodan Li ◽  
Karol Jan Nass ◽  
Ioana M Ilie ◽  
Manfred J Saller ◽  
Arnold J. M. Driessen ◽  
...  
Keyword(s):  
Crystal Structure ◽  
Molecular Dynamics ◽  
Thermotoga Maritima ◽  
Membrane Surface ◽  
Transmembrane Helix ◽  
Specific Interaction ◽  
Md Simulations ◽  
Dual Function ◽  
Sec Translocon

The evolutionary conserved YidC is a unique dual-function protein that adopts insertase and chaperone conformations. The TM1 helix of Escherichia coli YidC mediates the interaction between the YidC chaperone and the Sec translocon. Here, we report the first crystal structure of Thermotoga maritima YidC (TmYidC) including the TM1 helix (PDB ID: 6Y86). The TM1 helix lies on the periplasmic side of the bilayer forming an angle of about 15 degrees with the membrane surface. Our functional studies suggest a role of TM1 for the species-specific interaction with the Sec translocon. The reconstitution data and the superimposition of TmYidC with known YidC structures suggest an active insertase conformation for YidC. Molecular dynamics (MD) simulations of TmYidC provide evidence that the TM1 helix acts as a membrane anchor for the YidC insertase and highlight the flexibility of the C1 region underlining its ability to switch between insertase and chaperone conformations. A structure-based model is proposed to rationalize how YidC performs the insertase and chaperone functions by re-positioning of the TM1 helix and the other structural elements.

scholarly journals Molecular dynamics simulations of amino acid adsorption and transport at the acetonitrile–water–silica interface: the role of side chains

RSC Advances ◽  
2021 ◽  
Vol 11 (35) ◽  
pp. 21666-21677
Author(s):  
Yong-Peng Wang ◽  
Fei Liang ◽  
Shule Liu
Keyword(s):  
Molecular Dynamics ◽  
Liquid Chromatography ◽  
Amino Acid ◽  
Molecular Dynamics Simulations ◽  
Side Chains ◽  
Amino Acid Residues ◽  
Dynamics Simulations ◽  
Mechanism Of Separation

The solvation and transport of amino acid residues at liquid–solid interfaces have great importance for understanding the mechanism of separation of biomolecules in liquid chromatography.

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