Comparative Computational Analysis of Different Active Site Conformations and Substrates in a Chalcone Isomerase Catalyzed Reaction

2006 ◽  
Vol 110 (41) ◽  
pp. 20686-20692 ◽  
Author(s):  
J. Javier Ruiz-Pernía ◽  
Estanislao Silla ◽  
Iñaki Tuñón
Keyword(s):  
Active Site ◽  
Computational Analysis ◽  
Chalcone Isomerase

scholarly journals Mutational and computational analysis of the role of conserved residues in the active site of a family 18 chitinase

2004 ◽  
Vol 271 (2) ◽  
pp. 253-262 ◽  
Author(s):  
Bjornar Synstad ◽  
Sigrid Gaseidnes ◽  
Daan M. F. van Aalten ◽  
Gert Vriend ◽  
Jens E Nielsen ◽  
...  
Keyword(s):  
Active Site ◽  
Computational Analysis ◽  
Conserved Residues

scholarly journals Identification of Biosimilar for Trimethoprim – Andrographis paniculata Phytochemicals Inhibits Dihydrofolate Reductase (DHFR)

2021 ◽  
Vol 11 (6) ◽  
pp. 14142-14154
Keyword(s):  
Dihydrofolate Reductase ◽  
Active Site ◽  
Computational Analysis ◽  
Antimicrobial Property ◽  
Amino Acid Biosynthesis ◽  
Andrographis Paniculata ◽  
Active Site Residues ◽  
Acid Biosynthesis ◽  
Microbial Infections ◽  
Bioactive Phytochemicals

Staphylococcus aureus a pathogenic bacterium responsible for hospital and community-acquired infections. Trimethoprim is generally administrated for treating S.aureus infection in combination with sulfamethoxazole. But increasing antimicrobial resistance towards antibiotics is a major concern. Trimethoprim targets Dihydrofolate reductase (DHFR), a crucial enzyme involved in nucleic acid and amino acid biosynthesis pathways. DHFR catalyzes the conversion of dihydrofolate to tetrahydrofolate using NADH as a cofactor. Andrographis paniculata is a traditionally used medicinal plant for treating various ailments, including microbial infections. More than 25 bioactive phytochemicals have been reported to exhibit various activities. The aim of the present study is to identify the lead phytochemical(s) mediating antimicrobial property of A. paniculata by using computational analysis. Molecular docking of A.paniculata phytochemicals with wild and mutated DHFR were performed. Results reveal phytochemicals interact and exhibit strong binding affinity with active site residues of wild and mutated strains. 14-deoxy-11-oxoandrographolide showed binding energy greater than 10 kCal/mol with both strains. Further analysis of A. paniculata phytochemicals for their efficacy would lead to the development of potential drugs for the treatment of microbial infections.

ATP conformations and ion binding modes in the active site of anthrax edema factor: A computational analysis

2009 ◽  
Vol 77 (4) ◽  
pp. 971-983 ◽  
Author(s):  
Leandro Martínez ◽  
Elodie Laine ◽  
Thérèse E. Malliavin ◽  
Michael Nilges ◽  
Arnaud Blondel
Keyword(s):  
Active Site ◽  
Computational Analysis ◽  
Ion Binding ◽  
Binding Modes ◽  
Edema Factor

scholarly journals A computational analysis of SARS cysteine proteinase-octapeptide substrate interaction: implication for structure and active site binding mechanism

2009 ◽  
Vol 10 (Suppl 1) ◽  
pp. S48 ◽  
Author(s):  
Krongsakda Phakthanakanok ◽  
Khanok Ratanakhanokchai ◽  
Khin Kyu ◽  
Pornthep Sompornpisut ◽  
Aaron Watts ◽  
...  
Keyword(s):  
Active Site ◽  
Computational Analysis ◽  
Cysteine Proteinase ◽  
Binding Mechanism ◽  
Substrate Interaction ◽  
Site Binding

scholarly journals Computational analysis of the metal selectivity of matrix metalloproteinase 8

PLoS ONE ◽  
2020 ◽  
Vol 15 (12) ◽  
pp. e0243321
Author(s):  
Zheng Long
Keyword(s):  
Matrix Metalloproteinase ◽  
Active Site ◽  
Computational Analysis ◽  
Extracellular Matrices ◽  
Wild Type ◽  
Peptide Bonds ◽  
Metal Selectivity ◽  
Residue Number ◽  
Health And Disease ◽  
Metal Cofactors

Matrix metalloproteinase (MMP) is a class of metalloenzyme that cleaves peptide bonds in extracellular matrices. Their functions are important in both health and disease of animals. Here using quantum mechanics simulations of the MMP8 protein, the coordination chemistry of different metal cofactors is examined. Structural comparisons reveal that Jhan-Teller effects induced by Cu(II) coordination distorts the wild-type MMP8 active site corresponding to a significant reduction in activity observed in previous experiments. In addition, further analysis suggests that a histidine to glutamine mutation at residue number 197 can potentially allow the MMP8 protein to utilize Cu(II) in reactions. Simulations also demonstrates the requirement of a conformational change in the ligand before enzymatic cleavage. The insights provided here will assist future protein engineering efforts utilizing the MMP8 protein.

scholarly journals Directed Evolution of a Ketone Synthase for Efficient and Highly Selective Functionalization of Internal Alkenes by Accessing Reactive Carbocation Intermediates

2022 ◽  
Author(s):  
Sebastian Gergel ◽  
Jordi Soler ◽  
Alina Klein ◽  
Kai Schülke ◽  
Bernhard Hauer ◽  
...  
Keyword(s):  
Directed Evolution ◽  
Small Molecule ◽  
Active Site ◽  
Computational Analysis ◽  
Catalytic Cycle ◽  
Enantioselective Oxidation ◽  
Dynamical Network ◽  
Selective Functionalization ◽  
Synthetic Routes ◽  
Regioselective Oxidation

The direct regioselective oxidation of internal alkenes to ketones could simplify synthetic routes and solve a longstanding challenge in synthesis. This reaction is of particular importance because ketones are predominant moieties in valuable products as well as crucial intermediates in synthesis. Here we report the directed evolution of a ketone synthase that oxidizes internal alkenes directly to ketones with several thousand turnovers. The evolved ketone synthase benefits from more than a dozen crucial mutations, most of them distal to the active site. Computational analysis reveals that all these mutations collaborate to facilitate the formation of a highly reactive carbocation intermediate by generating a confined, rigid and preorganized active site through an enhanced dynamical network. The evolved ketone synthase fully exploits a catalytic cycle that has largely eluded small molecule catalysis and consequently enables various challenging functionalization reactions of internal alkenes. This includes the first catalytic, enantioselective oxidation of internal alkenes to ketones, as well as the formal asymmetric hydration and hydroamination of unactivated internal alkenes in combination with other biocatalysts.

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