Structural and Thermodynamic Studies on a Salt-bridge Triad in the NADP-binding Domain of Glutamate Dehydrogenase fromThermotoga maritima:  Cooperativity and Electrostatic Contribution to Stability†

Biochemistry ◽  
2002 ◽  
Vol 41 (52) ◽  
pp. 15524-15535 ◽  
Author(s):  
Joyce H. G. Lebbink ◽  
Valerio Consalvi ◽  
Roberta Chiaraluce ◽  
Kurt D. Berndt ◽  
Rudolf Ladenstein
Keyword(s):  
Glutamate Dehydrogenase ◽  
Salt Bridge ◽  
Binding Domain ◽  
Thermodynamic Studies ◽  
Electrostatic Contribution

Structural Role of a Buried Salt Bridge in the 434 Repressor DNA-binding Domain

1996 ◽  
Vol 264 (5) ◽  
pp. 1002-1012 ◽  
Author(s):  
Konstantin Pervushin ◽  
Martin Billeter ◽  
Gregg Siegal ◽  
Kurt Wüthrich
Keyword(s):  
Dna Binding ◽  
Salt Bridge ◽  
Binding Domain ◽  
Dna Binding Domain ◽  
Structural Role ◽  
434 Repressor

scholarly journals Insights into the Binding of Receptor-Binding Domain (RBD) of SARS-CoV-2 Wild Type and B.1.620 Variant with hACE2 Using Molecular Docking and Simulation Approaches

Biology ◽  
2021 ◽  
Vol 10 (12) ◽  
pp. 1310
Author(s):  
Ziyad Tariq Muhseen ◽  
Salim Kadhim ◽  
Yahiya Ibrahim Yahiya ◽  
Eid A. Alatawi ◽  
Faris F. Aba Alkhayl ◽  
...  
Keyword(s):  
Binding Energy ◽  
Hydrogen Bonds ◽  
Receptor Binding ◽  
Salt Bridge ◽  
Binding Domain ◽  
Total Binding Energy ◽  
Receptor Binding Domain ◽  
Wild Type ◽  
Docking Score ◽  
Total Binding

Recently, a new variant, B.1620, with mutations (S477N-E484K) in the spike protein’s receptor-binding domain (RBD) has been reported in Europe. In order to design therapeutic strategies suitable for B.1.620, further studies are required. A detailed investigation of the structural features and variations caused by these substitutions, that is, a molecular level investigation, is essential to uncover the role of these changes. To determine whether and how the binding affinity of ACE2–RBD is affected, we used protein–protein docking and all-atom simulation approaches. Our analysis revealed that B.1.620 binds more strongly than the wild type and alters the hydrogen bonding network. The docking score for the wild type was reported to be −122.6 +/− 0.7 kcal/mol, while for B.1.620, the docking score was −124.9 +/− 3.8 kcal/mol. A comparative binding investigation showed that the wild-type complex has 11 hydrogen bonds and one salt bridge, while the B.1.620 complex has 14 hydrogen bonds and one salt bridge, among which most of the interactions are preserved between the wild type and B.1.620. A dynamic analysis of the two complexes revealed stable dynamics, which corroborated the global stability trend, compactness, and flexibility of the three essential loops, providing a better conformational optimization opportunity and binding. Furthermore, binding free energy revealed that the wild type had a total binding energy of −51.14 kcal/mol, while for B.1.628, the total binding energy was −68.25 kcal/mol. The current findings based on protein complex modeling and bio-simulation methods revealed the atomic features of the B.1.620 variant harboring S477N and E484K mutations in the RBD and the basis for infectivity. In conclusion, the current study presents distinguishing features of B.1.620, which can be used to design structure-based drugs against the B.1.620 variant.

scholarly journals SARS-CoV-2 Omicron Spike Glycoprotein Receptor Binding Domain Exhibits Super-Binder Ability with ACE2 but not Convalescent Monoclonal Antibody

2021 ◽  
Author(s):  
Olaposi Idowu Omotuyi ◽  
Olubiyi Olujide ◽  
Oyekanmi Nash ◽  
Elizabeth O Afolabi ◽  
Babatunji Oyinloye ◽  
...  
Keyword(s):  
Monoclonal Antibody ◽  
Receptor Binding ◽  
Md Simulation ◽  
Center Of Mass ◽  
Salt Bridge ◽  
Binding Domain ◽  
Receptor Binding Domain ◽  
Spike Glycoprotein ◽  
Neutralizing Monoclonal Antibody ◽  
Complementarity Determining Region

Background: SARS-CoV-2, the causative virus for COVID-19 has now super-mutated into the Omicron (Om) variant. On its spike glycoprotein alone, more than 30 substitutions have been characterized with 15 within the receptor binding domain (RBD); It therefore calls to question the transmissibility and antibody escapability of Omicron. This study was setup to investigate the Omicron RBD interaction with ACE2 (host receptor) and a SARS-CoV-2 neutralizing monoclonal antibody (mAb). Methods: In-silico mutagenesis was used to generate the Om-RBD in complex with ACE2 or mAb from the wildtype. All-atom molecular dynamics (MD) simulation trajectories were analyzed for interaction. Results: MD trajectories showed that Omicron RBD has evolved into an efficient ACE2 binder, via pi-pi (Om-RBD-Y501/ACE2-Y41) and salt-bridge (Om-RBD-K493/ACE2-Y41) interactions. Conversely, in binding mAb, it has become less efficient (Center of mass distance of RBD from mAb complex, wildtype-RBD =30 A, Omicron-RBD= 41 A). Disruption of Om-RBD/mAb complex resulted from loose interaction between Om-RBD and the light chain complementarity-determining region residues. Conclusions: Omicron is expected to be better transmissible and less efficiently interacting with neutralizing convalescent mAbs. General significance: Our results elucidate the mechanisms for higher transmissibility in Omicron variant.

scholarly journals Characterisation ofSchizosaccharomyces pombe α-actinin

PeerJ ◽  
2016 ◽  
Vol 4 ◽  
pp. e1858 ◽  
Author(s):  
Barbara Addario ◽  
Linda Sandblad ◽  
Karina Persson ◽  
Lars Backman
Keyword(s):  
Salt Bridge ◽  
Structure And Function ◽  
Binding Domain ◽  
Actin Binding ◽  
Structural Domain ◽  
Structural Domains ◽  
Actin Binding Domain ◽  
Ef Hand ◽  
And Function ◽  
Spectrin Repeats

The actin cytoskeleton plays a fundamental role in eukaryotic cells. Its reorganization is regulated by a plethora of actin-modulating proteins, such as a-actinin. In higher organisms,α-actinin is characterized by the presence of three distinct structural domains: an N-terminal actin-binding domain and a C-terminal region with EF-hand motif separated by a central rod domain with four spectrin repeats. Sequence analysis has revealed that the central rod domain ofα-actinin from the fission yeastSchizosaccharomyces pombeconsists of only two spectrin repeats. To obtain a firmer understanding of the structure and function of this unconventionalα-actinin, we have cloned and characterized each structural domain. Our results show that this a-actinin isoform is capable of forming dimers and that the rod domain is required for this. However, its actin-binding and cross-linking activity appears less efficient compared to conventionalα-actinins. The solved crystal structure of the actin-binding domain indicates that the closed state is stabilised by hydrogen bonds and a salt bridge not present in otherα-actinins, which may reduce the affinity for actin.

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