Structural basis for the complete loss of GSK3β catalytic activity due to R96 mutation investigated by molecular dynamics study

2009 ◽  
Vol 75 (3) ◽  
pp. 671-681 ◽  
Author(s):  
Na Zhang ◽  
Yongjun Jiang ◽  
Jianwei Zou ◽  
Qingsen Yu ◽  
Wenna Zhao
Keyword(s):  
Molecular Dynamics ◽  
Catalytic Activity ◽  
Complete Loss ◽  
Structural Basis

scholarly journals Crystal structure of enolase fromDrosophila melanogaster

2017 ◽  
Vol 73 (4) ◽  
pp. 228-234 ◽  
Author(s):  
Congcong Sun ◽  
Baokui Xu ◽  
Xueyan Liu ◽  
Zhen Zhang ◽  
Zhongliang Su
Keyword(s):  
Crystal Structure ◽  
Catalytic Activity ◽  
Structural Basis ◽  
Molecular Replacement ◽  
Biological Processes ◽  
Conserved Residues ◽  
Dimer Interface ◽  
Open Conformation ◽  
Evolutionary Studies ◽  
Important Enzyme

Enolase is an important enzyme in glycolysis and various biological processes. Its dysfunction is closely associated with diseases. Here, the enolase fromDrosophila melanogaster(DmENO) was purified and crystallized. A crystal of DmENO diffracted to 2.0 Å resolution and belonged to space groupR32. The structure was solved by molecular replacement. Like most enolases, DmENO forms a homodimer with conserved residues in the dimer interface. DmENO possesses an open conformation in this structure and contains conserved elements for catalytic activity. This work provides a structural basis for further functional and evolutionary studies of enolase.

scholarly journals Biphasic Force-Regulated Phosphorylation Site Exposure and Unligation of ERM Bound with PSGL-1: A Novel Insight into PSGL-1 Signaling via Steered Molecular Dynamics Simulations

2020 ◽  
Vol 21 (19) ◽  
pp. 7064
Author(s):  
Jingjing Feng ◽  
Yan Zhang ◽  
Quhuan Li ◽  
Ying Fang ◽  
Jianhua Wu
Keyword(s):  
Molecular Dynamics ◽  
Tensile Force ◽  
Complex Structure ◽  
Phosphorylation Site ◽  
Steered Molecular Dynamics ◽  
Structural Basis ◽  
Quasi Equilibrium ◽  
Dissociation Probability ◽  
Transition Mechanism ◽  
Insight Into

The PSGL-1-actin cytoskeleton linker proteins ezrin/radixin/moesin (ERM), an adaptor between P-selectin glycoprotein ligand-1 (PSGL-1) and spleen tyrosine kinase (Syk), is a key player in PSGL-1 signal, which mediates the adhesion and recruitment of leukocytes to the activated endothelial cells in flow. Binding of PSGL-1 to ERM initials intracellular signaling through inducing phosphorylation of Syk, but effects of tensile force on unligation and phosphorylation site exposure of ERM bound with PSGL-1 remains unclear. To answer this question, we performed a series of so-called “ramp-clamp” steered molecular dynamics (SMD) simulations on the radixin protein FERM domain of ERM bound with intracellular juxtamembrane PSGL-1 peptide. The results showed that, the rupture force of complex pulled with constant velocity was over 250 pN, which prevented the complex from breaking in front of pull-induced exposure of phosphorylation site on immunoreceptor tyrosine activation motif (ITAM)-like motif of ERM; the stretched complex structure under constant tensile forces <100 pN maintained on a stable quasi-equilibrium state, showing a high mechano-stabilization of the clamped complex; and, in consistent with the force-induced allostery at clamped stage, increasing tensile force (<50 pN) would decrease the complex dissociation probability but facilitate the phosphorylation site exposure, suggesting a force-enhanced biophysical connectivity of PSGL-1 signaling. These force-enhanced characters in both phosphorylation and unligation of ERM bound with PSGL-1 should be mediated by a catch-slip bond transition mechanism, in which four residue interactions on binding site were involved. This study might provide a novel insight into the transmembrane PSGL-1 signal, its biophysical connectivity and molecular structural basis for cellular immune responses in mechano-microenvironment, and showed a rational SMD-based computer strategy for predicting structure-function relation of protein under loads.

Structural Basis of the Suppressed Catalytic Activity of Wild-type Human Glutathione Transferase T1-1 Compared to its W234R Mutant

2006 ◽  
Vol 355 (1) ◽  
pp. 96-105 ◽  
Author(s):  
Kaspars Tars ◽  
Anna-Karin Larsson ◽  
Abeer Shokeer ◽  
Birgit Olin ◽  
Bengt Mannervik ◽  
...  
Keyword(s):  
Catalytic Activity ◽  
Glutathione Transferase ◽  
Structural Basis ◽  
Wild Type

scholarly journals The Computational Analyses, Molecular Dynamics of Fatty-Acid Transport Mechanism to the CD36 Receptor: The Outcomes of the Mutation K164A on the Binding Domain, Structure and Function

2021 ◽  
Author(s):  
Jihane Akachar ◽  
Catherine Etchebest ◽  
Rachid Eljaoudi ◽  
Azeddine Ibrahimi
Keyword(s):  
Molecular Dynamics ◽  
Fatty Acids ◽  
Fatty Acid ◽  
Palmitic Acid ◽  
Conformational Changes ◽  
Structural Basis ◽  
Fatty Acid Transport ◽  
Acid Uptake ◽  
Wild Type ◽  
Cavity Structure

Abstract The transmembrane glycoprotein CD36, which is responsible of the metabolic disorders, and the elevated intake of fat induces lipid buildup, is a multifunctional scavenger receptor signaling those functions in high-affinity tissue uptake of long-chain fatty acids. In this study, we used series of molecular dynamics simulations of the wild type and mutants types K164A CD36 protein interacting with one Palmitic acid (PLM) besides simulations of the wild type interacting with the three PLM to find out the mechanism of the functioning of the complex CD36/Fatty acids and the unraveling of the role of the mutation. Additionally we determined whether Lys164, mostly exposed to protein surface, played important roles in fatty acid uptake. These simulations revealed, the conformational changes induced by Lys164 residue and the altered interactions induced by the mutagenesis of surface lysine that was badly influencing the folding, utility, solubility, and stability form of the variant. Furthermore, Lys164 residue provided the structural basis of forming an opening at the region of principal portal for the dissociation of palmitic acid. The results of our simulations revealed hole two fatty acids found in CD36 cavity structure and it was the most preferred to CD36 structure stabilization.

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