3D6G

Fc fragment of IgG1 (Herceptin) with protein-A mimetic peptide dendrimer ligand.

Summary for 3D6G

• Entry DOI: 10.2210/pdb3d6g/pdb
• Related: 1HZH 1L6X 2DTQ
• Descriptor: Ig gamma-1 chain C region, 2-acetamido-2-deoxy-beta-D-glucopyranose-(1-2)-alpha-D-mannopyranose-(1-3)-[2-acetamido-2-deoxy-beta-D-glucopyranose-(1-2)-alpha-D-mannopyranose-(1-6)]beta-D-mannopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-[alpha-L-fucopyranose-(1-6)]2-acetamido-2-deoxy-beta-D-glucopyranose, 2-[[(2S)-2,6-bis[[(2S)-2,6-bis[[(2R)-2-[[(2R,3R)-2-[[(2R)-2-amino-5-carbamimidamido-pentanoyl]amino]-3-hydroxy-butanoyl]amino]-3-(4-hydroxyphenyl)propanoyl]amino]hexanoyl]amino]hexanoyl]amino]ethanoic acid, ... (4 entities in total)
• Functional Keywords: fc fragment, igg1, glycosilated protein, protein a mimetic peptide dendrimer ligand, glycoprotein, immunoglobulin c region, immunoglobulin domain, secreted, immune system
• Biological source: Homo sapiens (Human)
• Total number of polymer chains: 2
• Total formula weight: 52645.82

Authors

Bujacz, A.D.,Redzynia, I.,Bujacz, G.D.,Dinon, F.,Pengo, P.,Fassina, G. (deposition date: 2008-05-19, release date: 2009-06-16, Last modification date: 2024-10-16)

Primary citation

Moiani, D.,Salvalaglio, M.,Cavallotti, C.,Bujacz, A.,Redzynia, I.,Bujacz, G.,Dinon, F.,Pengo, P.,Fassina, G.
Structural characterization of a Protein A mimetic peptide dendrimer bound to human IgG.
J.Phys.Chem.B, 113:16268-16275, 2009

PubMed Abstract: Understanding the chemical physical properties of protein binding sites is at the basis of the rational design of protein ligands. The hinge region of the Fc fragment of immunoglobulin G is an important and well characterized protein binding site, known to interact with several natural proteins and synthetic ligands. Here, we report structural evidence that a Staphylococcus aureus Protein A mimetic peptide dendrimer, deduced by a combinatorial approach, binds close to the Cgamma2/Cgamma3 interface of the constant fragment of a human IgG1 molecule, partially hindering the Protein A binding site. The X-ray analysis evidenced a primary binding site located between a terminal Arg residue of the ligand peptidic arm and a hydrophobic protein site consisting of Val308, Leu309, and His310. A molecular dynamic analysis of the model derived from the X-ray structure showed that in water at room temperature the complex is further stabilized by the formation of at least one more contact between a terminal Arg residue of the second arm of the peptide and the carboxylic group of a protein amino acid, such as Glu318, Asp312, or Asp280. It appears thus that stability of the Fc-dendrimer complex is determined by the synergetic formation of multiple bonds of different nature between the dendrimer arms and the protein accessible sites. The electrostatic and van der Waals energies of the complex were monitored during the MD simulations and confirmed the energetic stability of the two interactions.

PubMed: 19924842
DOI: 10.1021/jp909405b

Experimental method

X-RAY DIFFRACTION (2.3 Å)