Zhou_2021_Biomacromolecules__

Reference

Title : Synthesis, Characterization, and Simulation of Four-Armed Megamolecules - Zhou_2021_Biomacromolecules__
Author(s) : Zhou S , He P , Dhindwal S , Grum-Tokars VL , Li Y , Parker K , Modica JA , Bleher R , Dos Reis R , Zuchniarz J , Dravid VP , Voth GA , Roux B , Mrksich M
Ref : Biomacromolecules , : , 2021
Abstract :

This paper describes the synthesis, characterization, and modeling of a series of molecules having four protein domains attached to a central core. The molecules were assembled with the "megamolecule" strategy, wherein enzymes react with their covalent inhibitors that are substituted on a linker. Three linkers were synthesized, where each had four oligo(ethylene glycol)-based arms terminated in a para-nitrophenyl phosphonate group that is a covalent inhibitor for cutinase. This enzyme is a serine hydrolase and reacts efficiently with the phosphonate to give a new ester linkage at the Ser-120 residue in the active site of the enzyme. Negative-stain transmission electron microscopy (TEM) images confirmed the architecture of the four-armed megamolecules. These cutinase tetramers were also characterized by X-ray crystallography, which confirmed the active-site serine-phosphonate linkage by electron-density maps. Molecular dynamics simulations of the tetracutinase megamolecules using three different force field setups were performed and compared with the TEM observations. Using the Amberff99SB-disp + pH7 force field, the two-dimensional projection distances of the megamolecules were found to agree with the measured dimensions from TEM. The study described here, which combines high-resolution characterization with molecular dynamics simulations, will lead to a comprehensive understanding of the molecular structures and dynamics for this new class of molecules.

PubMedSearch : Zhou_2021_Biomacromolecules__
PubMedID: 33979120
Gene_locus related to this paper: fusso-cutas

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Citations formats

Zhou S, He P, Dhindwal S, Grum-Tokars VL, Li Y, Parker K, Modica JA, Bleher R, Dos Reis R, Zuchniarz J, Dravid VP, Voth GA, Roux B, Mrksich M (2021)
Synthesis, Characterization, and Simulation of Four-Armed Megamolecules
Biomacromolecules :

Zhou S, He P, Dhindwal S, Grum-Tokars VL, Li Y, Parker K, Modica JA, Bleher R, Dos Reis R, Zuchniarz J, Dravid VP, Voth GA, Roux B, Mrksich M (2021)
Biomacromolecules :