Genetic engineering of EcoRI mutants with altered amino acid residues in the DNA binding site: physicochemical investigations give evidence for an altered monomer/dimer equilibrium for the Gln144Lys145 and Gln144Lys145Lys200 mutants

Biochemistry ◽  
1989 ◽  
Vol 28 (6) ◽  
pp. 2667-2677 ◽  
Author(s):  
Robert Geiger ◽  
Thomas Rueter ◽  
Juergen Alves ◽  
Anja Fliess ◽  
Heiner Wolfes ◽  
...  
Keyword(s):  
Amino Acid ◽  
Dna Binding ◽  
Genetic Engineering ◽  
Binding Site ◽  
Amino Acid Residues ◽  
Dna Binding Site

scholarly journals Identifying amino acid residues that contribute to the cellular-DNA binding site on retroviral integrase

Virology ◽  
2009 ◽  
Vol 389 (1-2) ◽  
pp. 141-148 ◽  
Author(s):  
Matthew G. Nowak ◽  
Malgorzata Sudol ◽  
Noelle E. Lee ◽  
Wesley M. Konsavage ◽  
Michael Katzman
Keyword(s):  
Amino Acid ◽  
Dna Binding ◽  
Binding Site ◽  
Amino Acid Residues ◽  
Dna Binding Site ◽  
Cellular Dna ◽  
Retroviral Integrase

Schistosomal Sulfotransferase Interaction with Oxamniquine Involves Hybrid Mechanism of Induced-fit and Conformational Selection

2020 ◽  
Vol 16 (4) ◽  
pp. 451-459 ◽  
Author(s):  
Fortunatus C. Ezebuo ◽  
Ikemefuna C. Uzochukwu
Keyword(s):  
Molecular Dynamics ◽  
Amino Acid ◽  
Binding Energy ◽  
Binding Site ◽  
Conformational Dynamics ◽  
Side Chain ◽  
Amino Acid Residues ◽  
Conformational Selection ◽  
Hybrid Mechanism ◽  
Dynamics Simulations

Background: Sulfotransferase family comprises key enzymes involved in drug metabolism. Oxamniquine is a pro-drug converted into its active form by schistosomal sulfotransferase. The conformational dynamics of side-chain amino acid residues at the binding site of schistosomal sulfotransferase towards activation of oxamniquine has not received attention. Objective: The study investigated the conformational dynamics of binding site residues in free and oxamniquine bound schistosomal sulfotransferase systems and their contribution to the mechanism of oxamniquine activation by schistosomal sulfotransferase using molecular dynamics simulations and binding energy calculations. Methods: Schistosomal sulfotransferase was obtained from Protein Data Bank and both the free and oxamniquine bound forms were subjected to molecular dynamics simulations using GROMACS-4.5.5 after modeling it’s missing amino acid residues with SWISS-MODEL. Amino acid residues at its binding site for oxamniquine was determined and used for Principal Component Analysis and calculations of side-chain dihedrals. In addition, binding energy of the oxamniquine bound system was calculated using g_MMPBSA. Results: The results showed that binding site amino acid residues in free and oxamniquine bound sulfotransferase sampled different conformational space involving several rotameric states. Importantly, Phe45, Ile145 and Leu241 generated newly induced conformations, whereas Phe41 exhibited shift in equilibrium of its conformational distribution. In addition, the result showed binding energy of -130.091 ± 8.800 KJ/mol and Phe45 contributed -9.8576 KJ/mol. Conclusion: The results showed that schistosomal sulfotransferase binds oxamniquine by relying on hybrid mechanism of induced fit and conformational selection models. The findings offer new insight into sulfotransferase engineering and design of new drugs that target sulfotransferase.

scholarly journals Determinants for DNA-binding site recognition by the glucocorticoid receptor.

1992 ◽  
Vol 267 (35) ◽  
pp. 24941-24947
Author(s):  
J Zilliacus ◽  
A.P. Wright ◽  
U Norinder ◽  
J.A. Gustafsson ◽  
J Carlstedt-Duke
Keyword(s):  
Dna Binding ◽  
Glucocorticoid Receptor ◽  
Binding Site ◽  
Dna Binding Site ◽  
Site Recognition
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