Catalytic Mechanism of Human Ten-Eleven Translocation-2 (TET2) Enzyme: Effects of Conformational Changes, Electric Field, and Mutations

ACS Catalysis ◽  
2021 ◽  
Vol 11 (7) ◽  
pp. 3877-3890
Author(s):  
Sodiq O. Waheed ◽  
Shobhit S. Chaturvedi ◽  
Tatyana G. Karabencheva-Christova ◽  
Christo Z. Christov
Keyword(s):  
Electric Field ◽  
Conformational Changes ◽  
Catalytic Mechanism

Electric field-driven conformational changes in the elastin protein

2021 ◽  
Vol 23 (7) ◽  
pp. 4195-4204
Author(s):  
Debajyoti De ◽  
Nisha Pawar ◽  
Amar Nath Gupta
Keyword(s):  
Electric Field ◽  
Conformational Changes

Electric field masked the aggregation in elastin.

scholarly journals A Thermolabile Phospholipase B from Talaromyces marneffei GD-0079: Biochemical Characterization and Structure Dynamics Study

Biomolecules ◽  
2020 ◽  
Vol 10 (2) ◽  
pp. 231 ◽  
Author(s):  
Rabia Durrani ◽  
Faez Iqbal Khan ◽  
Shahid Ali ◽  
Yonghua Wang ◽  
Bo Yang
Keyword(s):  
Fatty Acids ◽  
Conformational Changes ◽  
Catalytic Mechanism ◽  
Biochemical Characterization ◽  
Structural Information ◽  
Expression System ◽  
Talaromyces Marneffei ◽  
Structure Dynamics ◽  
Phospholipase B ◽  
Hydrolysis Of

Phospholipase B (EC 3.1.1.5) are a distinctive group of enzymes that catalyzes the hydrolysis of fatty acids esterified at the sn-1 and sn-2 positions forming free fatty acids and lysophospholipids. The structural information and catalytic mechanism of phospholipase B are still not clear. Herein, we reported a putative phospholipase B (TmPLB1) from Talaromyces marneffei GD-0079 synthesized by genome mining library. The gene (TmPlb1) was expressed and the TmPLB1 was purified using E. coli shuffle T7 expression system. The putative TmPLB1 was purified by affinity chromatography with a yield of 13.5%. The TmPLB1 showed optimum activity at 35 °C and pH 7.0. The TmPLB1 showed enzymatic activity using Lecithin (soybean > 98% pure), and the hydrolysis of TmPLB1 by 31P NMR showed phosphatidylcholine (PC) as a major phospholipid along with lyso-phospholipids (1-LPC and 2-LPC) and some minor phospholipids. The molecular modeling studies indicate that its active site pocket contains Ser125, Asp183 and His215 as the catalytic triad. The structure dynamics and simulations results explained the conformational changes associated with different environmental conditions. This is the first report on biochemical characterization and structure dynamics of TmPLB1 enzyme. The present study could be helpful to utilize TmPLB1 in food industry for the determination of food components containing phosphorus. Additionally, such enzyme could also be useful in Industry for the modifications of phospholipids.

Improving the analysis of NMR spectra tracking pH-induced conformational changes: Removing artefacts of the electric field on the NMR chemical shift

2009 ◽  
Vol 78 (4) ◽  
pp. 971-984 ◽  
Author(s):  
Predrag Kukić ◽  
Damien Farrell ◽  
Chresten R. Søndergaard ◽  
Una Bjarnadottir ◽  
John Bradley ◽  
...  
Keyword(s):  
Chemical Shift ◽  
Electric Field ◽  
Conformational Changes ◽  
Nmr Spectra ◽  
Nmr Chemical Shift

ELECTRIC-FIELD DEPENDENCE OF MOLECULAR CONFORMATIONS OBSERVED BY USING SCANNING TUNNELING MICROSCOPY

NANO ◽  
2008 ◽  
Vol 03 (02) ◽  
pp. 83-94
Author(s):  
XIAO JING MA ◽  
RUI ZHANG ◽  
YONG TAO SHEN ◽  
XIAO HUI QIU ◽  
YAN LIAN YANG ◽  
...  
Keyword(s):  
Electric Field ◽  
Scanning Tunneling Microscopy ◽  
Functional Groups ◽  
Field Dependence ◽  
Conformational Changes ◽  
Supramolecular Structures ◽  
Scanning Tunneling ◽  
Tunneling Microscopy ◽  
Molecular Conformations ◽  
Electric Field Dependence

We review the progress in observation of electrically induced conformational changes of a range of single molecules and molecular assemblies using scanning tunneling microscopy (STM). Recent results using species with optical active functional groups and supramolecular structures confirmed the previously observed effects that the cholesterol molecules with soft linkers have the conformational bistability when switching the bias polarity, while no discernable changes were observed for the mesogen molecules, containing rigid linking units. In addition, it was also observed that the linker units could have appreciable impacts on the assembling characteristics.

PLP undergoes conformational changes during the course of an enzymatic reaction

2014 ◽  
Vol 70 (2) ◽  
pp. 596-606 ◽  
Author(s):  
Ho-Phuong-Thuy Ngo ◽  
Nuno M. F. S. A. Cerqueira ◽  
Jin-Kwang Kim ◽  
Myoung-Ki Hong ◽  
Pedro Alexandrino Fernandes ◽  
...  
Keyword(s):  
Conformational Change ◽  
Conformational Changes ◽  
Catalytic Mechanism ◽  
Enzymatic Reaction ◽  
Nucleophilic Attack ◽  
The Novel ◽  
X Ray ◽  
X Ray Crystallography ◽  
Starting Point ◽  
High Level

Numerous enzymes, such as the pyridoxal 5′-phosphate (PLP)-dependent enzymes, require cofactors for their activities. Using X-ray crystallography, structural snapshots of the L-serine dehydratase catalytic reaction of a bacterial PLP-dependent enzyme were determined. In the structures, the dihedral angle between the pyridine ring and the Schiff-base linkage of PLP varied from 18° to 52°. It is proposed that the organic cofactor PLP directly catalyzes reactions by active conformational changes, and the novel catalytic mechanism involving the PLP cofactor was confirmed by high-level quantum-mechanical calculations. The conformational change was essential for nucleophilic attack of the substrate on PLP, for concerted proton transfer from the substrate to the protein and for directing carbanion formation of the substrate. Over the whole catalytic cycle, the organic cofactor catalyzes a series of reactions, like the enzyme. The conformational change of the PLP cofactor in catalysis serves as a starting point for identifying the previously unknown catalytic roles of organic cofactors.

scholarly journals Structural insights into SETD3-mediated histidine methylation on β-actin

2018 ◽  
Author(s):  
Qiong Guo ◽  
Shanhui Liao ◽  
Sebastian Kwiatkowski ◽  
Weronika Tomaka ◽  
Huijuan Yu ◽  
...  
Keyword(s):  
Pulmonary Hypertension ◽  
Enzyme Activity ◽  
Small Molecule ◽  
Conformational Changes ◽  
Catalytic Mechanism ◽  
Site Directed Mutagenesis ◽  
Directed Mutagenesis ◽  
Domain Protein ◽  
First Time ◽  
Structural Insights

SETD3 is a member of SET (Su(var)3-9, Enhancer of zeste, and Trithorax) domain protein superfamily and plays important roles in hypoxic pulmonary hypertension, muscle differentiation, and carcinogenesis. Recently, we have identified SETD3 as the actin-specific methyltransferase that methylates the N3 of His73 on β-actin. Here we present two structures of S-adenosyl-L-homocysteine-bound SETD3 in complex with either an unmodified β-actin peptide or its His-methylated variant. Structural analyses supported by the site-directed mutagenesis experiments and the enzyme activity assays indicated that the recognition and methylation of β-actin by SETD3 is highly sequence specific, and both SETD3 and β-actin adopt pronounce conformational changes upon binding to each other. In conclusion, the data show for the first time a catalytic mechanism of SETD3-mediated histidine methylation in β-actin, which not only throws light on protein histidine methylation phenomenon, but also facilitates the design of small molecule inhibitors of SETD3.

scholarly journals Receptor Binding Domain (RBD) Structural Susceptibility in the SARS-CoV-2 Virus Spike Protein Exposed to a Pulsed Electric Field

2021 ◽  
Vol 8 (2) ◽  
pp. 177-182
Author(s):  
D. Osorio-González ◽  
V. J. Muñiz-Orozco ◽  
C. P. González ◽  
M. Fuentes-Acosta ◽  
J. Mulia-Rodríguez ◽  
...  
Keyword(s):  
Electric Field ◽  
Receptor Binding ◽  
Conformational Changes ◽  
In Silico Analysis ◽  
Pulsed Electric Field ◽  
Binding Domain ◽  
Chemical Components ◽  
Receptor Binding Domain ◽  
Viral Inhibition ◽  
Starting Point

SARS-CoV-2 is responsible for causing the Coronavirus disease 2019 (COVID-19) pandemic, which has so far infected more than thirty million people and caused almost a million deaths. For this reason, it has been a priority to stop the transmission of the outbreak through preventive measures, such as surface disinfection, and to establish bases for the design of an effective disinfection technique without chemical components. In this study, we performed in silico analysis to identify the conformational alterations of the SARS-CoV-2 Spike Receptor Binding Domain (RBD) caused by the effect of a pulsed electric field at two different intensities. We found that both stimuli, especially the one with the highest angular frequency and amplitude, modified the electrical charge distribution in the RBD surface and the number of hydrogen bonds. Moreover, the secondary structure was significantly affected, with a decrease of the structured regions, particularly the regions with residues involved in recognizing and interacting with the receptor ACE2. Since many regions suffered conformational changes, we calculated RMSF and ΔRMSF to identify the regions and residues with larger fluctuations and higher flexibility. We found that regions conformed by 353-372, 453-464, and 470-490 amino acid residues fluctuate the most, where the first is considered a therapeutic target, and the last has alreadybeen characterized for its flexibility. Our results indicate that a pulsed electric field can cause loss of stability in the Spike-RBD, and we were able to identify the vulnerable sites to be used as a starting point for the development of viral inhibition or inactivation mechanisms.

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