In‐Silico Screening and Microsecond Molecular Dynamics Simulations to Identify Single Point Mutations That Destabilize β‐hexosaminidase A ( HexA ) Causing Tay‐Sachs Disease

2021 ◽  
Author(s):  
Ahmad Almanasra ◽  
Brandon Havranek ◽  
Shahidul M. Islam
Keyword(s):  
Molecular Dynamics ◽  
Molecular Dynamics Simulations ◽  
In Silico ◽  
Single Point ◽  
Point Mutations ◽  
In Silico Screening ◽  
Tay Sachs Disease ◽  
Hexosaminidase A ◽  
Single Point Mutations ◽  
Dynamics Simulations

Cupin Variants as Macromolecular Ligand Library for Stereoselective Michael Addition of Nitroalkanes

2019 ◽  
Author(s):  
Nobutaka Fujieda ◽  
Miho Yuasa ◽  
Yosuke Nishikawa ◽  
Genji Kurisu ◽  
Shinobu Itoh ◽  
...  
Keyword(s):  
Michael Addition ◽  
In Silico ◽  
Addition Reaction ◽  
Single Point ◽  
Point Mutations ◽  
Unsaturated Ketone ◽  
Michael Addition Reaction ◽  
Beta Barrel ◽  
Cupin Superfamily ◽  
Single Point Mutations

Cupin superfamily proteins (TM1459) work as a macromolecular ligand framework with a double-stranded beta-barrel structure ligating to a Cu ion through histidine side chains. Variegating the first coordination sphere of TM1459 revealed that H52A and H54A/H58A mutants effectively catalyzed the diastereo- and enantio-selective Michael addition reaction of nitroalkanes to an α,β-unsaturated ketone. Moreover, in silico substrate docking signified C106N and F104W single-point mutations, which inverted the diastereoselectivity of H52A and further improved the stereoselectivity of H54A/H58A, respectively.

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