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Crowning proteins: modulating the protein surface properties using crown ethers.

Lee CC, Maestre-Reyna M, Hsu KC, Wang HC, Liu CI, Jeng WY, Lin LL, Wood R, Chou CC, Yang JM, Wang AH - Angew. Chem. Int. Ed. Engl. (2014)

Bottom Line: We elucidated the crystal structures of several protein-crown ether co-crystals grown in the presence of 18-crown-6.We then employed biophysical methods and molecular dynamics simulations to compare these complexes with the corresponding apoproteins and with similar complexes with ring-shaped low-molecular-weight polyethylene glycols.Consequently, we propose that crown ethers can be used to modulate a wide variety of protein surface behaviors, such as oligomerization, domain-domain interactions, stabilization in organic solvents, and crystallization.

View Article: PubMed Central - PubMed

Affiliation: Institute of Biological Chemistry, Academia Sinica, 128 Academia Road, Section 2, Nankang, Taipei 11529 (Taiwan); Core Facilities for Protein Structural Analysis, Academia Sinica, 128 Academia Road, Section 2, Nankang, Taipei 11529 (Taiwan).

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Examples of lmwPEGs adopting a ring-shaped conformation in a variety of deposited crystal structures. Three examples of PDB entries containing ring-shaped lmwPEGs: a) Pin1R14A (2ITK), b) human myosin light chain kinase (2X4F), and c) dTMP kinase (2PLR). Different protein chains are colored in gray, green, and purple. Chains within an asymmetric unit are capitalized, while crystallographic equivalents are marked with an asterisk (*). d) Top: PEG200 in its linear conformation. PEG200 was bound by 2PLR. Bottom: 18-crown-6 ether is a circular molecule, which is strikingly similar to ring-shaped PEG200. Molecular weights and formulas are taken from Pubchem (CID 62551 for PEG200, and CID 28557 for 18-crown-6).
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fig01: Examples of lmwPEGs adopting a ring-shaped conformation in a variety of deposited crystal structures. Three examples of PDB entries containing ring-shaped lmwPEGs: a) Pin1R14A (2ITK), b) human myosin light chain kinase (2X4F), and c) dTMP kinase (2PLR). Different protein chains are colored in gray, green, and purple. Chains within an asymmetric unit are capitalized, while crystallographic equivalents are marked with an asterisk (*). d) Top: PEG200 in its linear conformation. PEG200 was bound by 2PLR. Bottom: 18-crown-6 ether is a circular molecule, which is strikingly similar to ring-shaped PEG200. Molecular weights and formulas are taken from Pubchem (CID 62551 for PEG200, and CID 28557 for 18-crown-6).

Mentions: As structural analogues for CRs, the circa 2000 lmwPEG (MW<600 g mol−1) structures deposited in the Protein Data Bank (PDB) are prime candidates for exploring the potential of cyclic compounds in crystallographic applications (Figure 1). LmwPEGs show two distinct conformational types: linear lmwPEGs presenting an extended conformation, and ring-shaped lmwPEGs with a configuration similar to the CR structure. In the latter type, they often form Van der Waals (VdW) contacts with aromatic or aliphatic residues (Figure 1), or they coordinate primary amines (lysine) or guanidinium moieties (arginine) (Figure 1 b). Further, our bio-informatic studies indicated that 68 % of all ring-shaped lmwPEGs, but only 58 % of linear PEGs, mediated protein–protein contacts in the crystal. These observations suggested that CRs with similar physico-chemical properties to lmwPEGs (Figure 1 d) may be more constrained and therefore better chelators and VdW partners to protein surfaces.


Crowning proteins: modulating the protein surface properties using crown ethers.

Lee CC, Maestre-Reyna M, Hsu KC, Wang HC, Liu CI, Jeng WY, Lin LL, Wood R, Chou CC, Yang JM, Wang AH - Angew. Chem. Int. Ed. Engl. (2014)

Examples of lmwPEGs adopting a ring-shaped conformation in a variety of deposited crystal structures. Three examples of PDB entries containing ring-shaped lmwPEGs: a) Pin1R14A (2ITK), b) human myosin light chain kinase (2X4F), and c) dTMP kinase (2PLR). Different protein chains are colored in gray, green, and purple. Chains within an asymmetric unit are capitalized, while crystallographic equivalents are marked with an asterisk (*). d) Top: PEG200 in its linear conformation. PEG200 was bound by 2PLR. Bottom: 18-crown-6 ether is a circular molecule, which is strikingly similar to ring-shaped PEG200. Molecular weights and formulas are taken from Pubchem (CID 62551 for PEG200, and CID 28557 for 18-crown-6).
© Copyright Policy - open-access
Related In: Results  -  Collection

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getmorefigures.php?uid=PMC4288931&req=5

fig01: Examples of lmwPEGs adopting a ring-shaped conformation in a variety of deposited crystal structures. Three examples of PDB entries containing ring-shaped lmwPEGs: a) Pin1R14A (2ITK), b) human myosin light chain kinase (2X4F), and c) dTMP kinase (2PLR). Different protein chains are colored in gray, green, and purple. Chains within an asymmetric unit are capitalized, while crystallographic equivalents are marked with an asterisk (*). d) Top: PEG200 in its linear conformation. PEG200 was bound by 2PLR. Bottom: 18-crown-6 ether is a circular molecule, which is strikingly similar to ring-shaped PEG200. Molecular weights and formulas are taken from Pubchem (CID 62551 for PEG200, and CID 28557 for 18-crown-6).
Mentions: As structural analogues for CRs, the circa 2000 lmwPEG (MW<600 g mol−1) structures deposited in the Protein Data Bank (PDB) are prime candidates for exploring the potential of cyclic compounds in crystallographic applications (Figure 1). LmwPEGs show two distinct conformational types: linear lmwPEGs presenting an extended conformation, and ring-shaped lmwPEGs with a configuration similar to the CR structure. In the latter type, they often form Van der Waals (VdW) contacts with aromatic or aliphatic residues (Figure 1), or they coordinate primary amines (lysine) or guanidinium moieties (arginine) (Figure 1 b). Further, our bio-informatic studies indicated that 68 % of all ring-shaped lmwPEGs, but only 58 % of linear PEGs, mediated protein–protein contacts in the crystal. These observations suggested that CRs with similar physico-chemical properties to lmwPEGs (Figure 1 d) may be more constrained and therefore better chelators and VdW partners to protein surfaces.

Bottom Line: We elucidated the crystal structures of several protein-crown ether co-crystals grown in the presence of 18-crown-6.We then employed biophysical methods and molecular dynamics simulations to compare these complexes with the corresponding apoproteins and with similar complexes with ring-shaped low-molecular-weight polyethylene glycols.Consequently, we propose that crown ethers can be used to modulate a wide variety of protein surface behaviors, such as oligomerization, domain-domain interactions, stabilization in organic solvents, and crystallization.

View Article: PubMed Central - PubMed

Affiliation: Institute of Biological Chemistry, Academia Sinica, 128 Academia Road, Section 2, Nankang, Taipei 11529 (Taiwan); Core Facilities for Protein Structural Analysis, Academia Sinica, 128 Academia Road, Section 2, Nankang, Taipei 11529 (Taiwan).

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