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Synthesis, Characterization, and Simulation of Four-Armed Megamolecules
- Source :
- Biomacromolecules. 22(6)
- Publication Year :
- 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.
- Subjects :
- Cutinase
Polymers and Plastics
Organophosphonates
Bioengineering
02 engineering and technology
010402 general chemistry
Crystallography, X-Ray
01 natural sciences
Biomaterials
chemistry.chemical_compound
Molecular dynamics
Protein Domains
Catalytic Domain
Materials Chemistry
Molecule
biology
Molecular Structure
Chemistry
Active site
Serine hydrolase
021001 nanoscience & nanotechnology
Phosphonate
0104 chemical sciences
Crystallography
Covalent bond
biology.protein
0210 nano-technology
Linker
Subjects
Details
- ISSN :
- 15264602
- Volume :
- 22
- Issue :
- 6
- Database :
- OpenAIRE
- Journal :
- Biomacromolecules
- Accession number :
- edsair.doi.dedup.....d58028196c136a3a59628d71c961eeda