How Processive Enzymes Work: the Application of Molecular Dynamics Simulation to Study the Catalytic Mechanism

2012 ◽  
Vol 42 (8) ◽  
pp. 603-612
Author(s):  
LuShan WANG ◽  
LongQiang PAN ◽  
Bin HUANG ◽  
CunLiang GENG ◽  
PeiJi GAO ◽  
...  
Keyword(s):  
Molecular Dynamics ◽  
Molecular Dynamics Simulation ◽  
Catalytic Mechanism ◽  
Dynamics Simulation

Insights into the mode of flavin mononucleotide binding and catalytic mechanism of bacterial chromate reductases: A molecular dynamics simulation study

2019 ◽  
Vol 120 (10) ◽  
pp. 16990-17005
Author(s):  
Sukanta Kumar Pradhan ◽  
Nihar Ranjan Singh ◽  
Budheswar Dehury ◽  
Debashis Panda ◽  
Mahendra Kumar Modi ◽  
...  
Keyword(s):  
Molecular Dynamics ◽  
Molecular Dynamics Simulation ◽  
Simulation Study ◽  
Catalytic Mechanism ◽  
Dynamics Simulation ◽  
Flavin Mononucleotide ◽  
Chromate Reductases

Influence of metal cofactors and water on the catalytic mechanism of creatininase-creatinine in aqueous solution from molecular dynamics simulation and quantum study

2010 ◽  
Vol 24 (10) ◽  
pp. 879-886 ◽  
Author(s):  
Vannajan Sanghiran Lee ◽  
Kanchanok Kodchakorn ◽  
Jitrayut Jitonnom ◽  
Piyarat Nimmanpipug ◽  
Prachya Kongtawelert ◽  
...  
Keyword(s):  
Molecular Dynamics ◽  
Aqueous Solution ◽  
Molecular Dynamics Simulation ◽  
Catalytic Mechanism ◽  
Dynamics Simulation ◽  
Metal Cofactors

scholarly journals Reductive inactivation of the hemiaminal pharmacophore for resistance against tetrahydroisoquinoline antibiotics

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Wan-Hong Wen ◽  
Yue Zhang ◽  
Ying-Ying Zhang ◽  
Qian Yu ◽  
Chu-Chu Jiang ◽  
...  
Keyword(s):  
Crystal Structure ◽  
Molecular Dynamics ◽  
Antibiotic Resistance ◽  
Molecular Dynamics Simulation ◽  
Biosynthetic Pathway ◽  
Catalytic Mechanism ◽  
Simulation Analysis ◽  
Damage Control ◽  
Dynamics Simulation ◽  
Self Defense

AbstractAntibiotic resistance is becoming one of the major crises, among which hydrolysis reaction is widely employed by bacteria to destroy the reactive pharmacophore. Correspondingly, antibiotic producer has canonically co-evolved this approach with the biosynthetic capability for self-resistance. Here we discover a self-defense strategy featuring with reductive inactivation of hemiaminal pharmacophore by short-chain dehydrogenases/reductases (SDRs) NapW and homW, which are integrated with the naphthyridinomycin biosynthetic pathway. We determine the crystal structure of NapW·NADPH complex and propose a catalytic mechanism by molecular dynamics simulation analysis. Additionally, a similar detoxification strategy is identified in the biosynthesis of saframycin A, another member of tetrahydroisoquinoline (THIQ) antibiotics. Remarkably, similar SDRs are widely spread in bacteria and able to inactive other THIQ members including the clinical anticancer drug, ET-743. These findings not only fill in the missing intracellular events of temporal-spatial shielding mode for cryptic self-resistance during THIQs biosynthesis, but also exhibit a sophisticated damage-control in secondary metabolism and general immunity toward this family of antibiotics.

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