6EGZ

Crystal structure of cytochrome c in complex with di-PEGylated sulfonatocalix[4]arene

Summary for 6EGZ

• Entry DOI: 10.2210/pdb6egz/pdb
• Related: 6EGY
• Descriptor: Cytochrome c iso-1, HEME C, di-PEGylated sulfonatocalix[4]arene, ... (6 entities in total)
• Functional Keywords: non-covalent pegylation, sulfonato calix[4]arene, cone and partial cone conformations, electron transport
• Biological source: Saccharomyces cerevisiae (Baker's yeast)
• Total number of polymer chains: 2
• Total formula weight: 33231.29

Authors

Mummidivarapu, V.V.S.,Rennie, M.L.,Crowley, P.B. (deposition date: 2017-09-12, release date: 2018-10-10, Last modification date: 2024-11-20)

Primary citation

Mummidivarapu, V.V.S.,Rennie, M.L.,Doolan, A.M.,Crowley, P.B.
Noncovalent PEGylation via Sulfonatocalix[4]arene-A Crystallographic Proof.
Bioconjug.Chem., 29:3999-4003, 2018

PubMed Abstract: Noncovalent or supramolecular PEGylation, in combination with the site of administration, has great potential to increase the half-life of therapeutic proteins. To date, a variety of noncovalent PEGylation strategies have been devised. However, questions remain concerning the nature of the protein-PEG interaction. Here, we report structural analyses of a model system that comprised the lysine-rich cytochrome c and two PEGylated variants of sulfonatocalix[4]arene. Complex formation was characterized in solution by NMR spectroscopy. It was found that mono- or di-PEGylated sulfonatocalix[4]arene bound the protein similar to the parent calixarene. X-ray crystal structures at <2.7 Å resolution of the PEGylated derivatives in complex with cytochrome c revealed that the PEG chains were mostly disordered or encapsulated within the calixarene cavity. These results suggest that there was minimal interaction between the PEG and the protein surface, providing further evidence in favor of PEG maintaining a random coil conformation.

PubMed: 30445810
DOI: 10.1021/acs.bioconjchem.8b00769

Experimental method

X-RAY DIFFRACTION (2.17 Å)