Evolution of an antibiotic resistance enzyme constrained by stability and activity trade-offs.

By Xiaojun Wang, G. Minasov, Brian K. Shoichet. 2002

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Coevolutionary Landscape Inference and the Context-Dependence of Mutations in Beta-Lactamase TEM-1 (2015, methodology): “[63] Xiaojun Wang, George Minasov, and Brian K Shoichet.”
Exploring protein fitness landscapes by directed evolution (2009, background): “Such trade-offs have also been shown to constrain the evolution of antibiotic resistance enzyme”
Predicting the locations of cryptic pockets from single protein structures using the PocketMiner graph neural network (2022, background): “Proteins exist in an equilibrium between different structures, including experimentally-derived structures that lack cryptic pockets (left, PDB ID 1JWP) 25 and those with open cryptic pockets (right, PDB ID 1PZO) 11 .”
Patterns of Epistasis between Beneficial Mutations in an Antibiotic Resistance Gene (2013, background): “S4, Supplementary Material online) is consistent with a key role of enzyme stability in determining enzyme function, as well as with the predicted trade-off between enzyme stability and other key properties, such as enzyme activity, leading to antagonistically pleiotropic effects of beneficial mutat”
Predicting locations of cryptic pockets from single protein structures using the PocketMiner graph neural network (2023, background): “A Proteins exist in an equilibrium between different structures, including experimentally derived structures that lack cryptic pockets (left, PDB ID 1JWP) 71 and those with open cryptic pockets (right, PDB ID 1PZO) 4 .”