Theoretical investigation on binding process of allophanate to allophanate hydrolase

Zhang, Zidong; Zhang, Ji-Long; Zheng, Qing‐Chuan; Kong, Chui‐Peng; Li, Zhengqiang; Zhang, Hongxing; Ma, Jun

doi:10.1007/s40242-015-5108-0

Cited by 2 publications

(2 citation statements)

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“…Zhang et al obtained a free energy change of ∼21 kcal/mol for the unbinding of an acetamidomethylene substrate (containing two carboxylate groups) from a hydrolase . In another study, the binding of allophanate (with one carboxylate group) in allophanate hydrolase was found to involve a free energy change of ∼17 kcal/mol . Thus, the value of ∼23 kcal/mol for the WT AMDase reported here is in line with these earlier investigations concerning the binding/unbinding of mono- or dicarboxylate substrates in enzymes.…”

Section: Resultssupporting

confidence: 91%

“…74 In another study, the binding of allophanate (with one carboxylate group) in allophanate hydrolase was found to involve a free energy change of ∼17 kcal/mol. 75 Thus, the value of ∼23 kcal/ mol for the WT AMDase reported here is in line with these earlier investigations concerning the binding/unbinding of mono-or dicarboxylate substrates in enzymes.…”

Section: ■ Computational Methodssupporting

confidence: 92%

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Molecular Dynamics and Free Energy Simulations of Phenylacetate and CO₂ Release from AMDase and Its G74C/C188S Mutant: A Possible Rationale for the Reduced Activity of the Latter

Karmakar

Balasubramanian

2016

J. Phys. Chem. B

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Arylmalonate decarboxylase (AMDase) catalyzes the decarboxylation of α-aryl-α-methyl malonates to produce optically pure α-arylpropionates of industrial and medicinal importance. Herein, atomistic molecular dynamics simulations have been carried out to delineate the mechanism of the release of product molecules phenylacetate (PAC) and carbon dioxide (CO), from the wild-type (WT) and its G74C/C188S mutant enzymes. Both of the product molecules follow a crystallographically characterized solvent-accessible channel to come out of the protein interior. A higher free energy barrier for the release of PAC from G74C/C188S compared to that in the WT is consistent with the experimentally observed compromised efficiency of the mutant. The release of CO precedes that of PAC; free energy barriers for CO and PAC release in the WT enzyme are calculated to be ∼1-2 and ∼23 kcal/mol, respectively. Postdecarboxylation, CO moves toward a hydrophobic pocket formed by Pro 14, Leu 38, Leu 40, Leu 77, and the side chain of Tyr 48 which serves as its temporary "reservoir". CO releases following a channel mainly decorated by apolar residues, unlike in the case of oxalate decarboxylase where polar residues mediate its transport.

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Section: Resultssupporting

confidence: 91%

Section: ■ Computational Methodssupporting

confidence: 92%

Molecular Dynamics and Free Energy Simulations of Phenylacetate and CO₂ Release from AMDase and Its G74C/C188S Mutant: A Possible Rationale for the Reduced Activity of the Latter

Karmakar

Balasubramanian

2016

J. Phys. Chem. B

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A comparative MP2 study between water- and acid-assisted proton transfer: allophanic acid as a case of study

et al. 2016

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Theoretical investigation on binding process of allophanate to allophanate hydrolase

Cited by 2 publications

References 35 publications

Molecular Dynamics and Free Energy Simulations of Phenylacetate and CO₂ Release from AMDase and Its G74C/C188S Mutant: A Possible Rationale for the Reduced Activity of the Latter

Molecular Dynamics and Free Energy Simulations of Phenylacetate and CO₂ Release from AMDase and Its G74C/C188S Mutant: A Possible Rationale for the Reduced Activity of the Latter

A comparative MP2 study between water- and acid-assisted proton transfer: allophanic acid as a case of study

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Theoretical investigation on binding process of allophanate to allophanate hydrolase

Cited by 2 publications

References 35 publications

Molecular Dynamics and Free Energy Simulations of Phenylacetate and CO2 Release from AMDase and Its G74C/C188S Mutant: A Possible Rationale for the Reduced Activity of the Latter

Molecular Dynamics and Free Energy Simulations of Phenylacetate and CO2 Release from AMDase and Its G74C/C188S Mutant: A Possible Rationale for the Reduced Activity of the Latter

A comparative MP2 study between water- and acid-assisted proton transfer: allophanic acid as a case of study

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Molecular Dynamics and Free Energy Simulations of Phenylacetate and CO₂ Release from AMDase and Its G74C/C188S Mutant: A Possible Rationale for the Reduced Activity of the Latter

Molecular Dynamics and Free Energy Simulations of Phenylacetate and CO₂ Release from AMDase and Its G74C/C188S Mutant: A Possible Rationale for the Reduced Activity of the Latter