5OWP

Crystal structure of glycopeptide "GVTSAfPDT*RPAP" in complex with scFv-SM3

Summary for 5OWP

• Entry DOI: 10.2210/pdb5owp/pdb
• Descriptor: Ig heavy chain V-III region J606,Ig lambda-1 chain V region H2020, 5,6-DIHYDRO-BENZO[H]CINNOLIN-3-YLAMINE, 1,2-ETHANEDIOL, ... (5 entities in total)
• Functional Keywords: immune system
• Biological source: Mus musculus (Mouse); More
• Total number of polymer chains: 2
• Total formula weight: 26998.60

Authors

Bermejo, I.A.,Albuquerque, I.S.,Somovilla, V.J.,Martinez-Saez, N.,Castro-Lopez, J.,Garcia-Martin, F.,Hinou, H.,Nishimura, S.,Jimenez-Barbero, J.,Asensio, J.L.,Avenoza, A.,Busto, J.H.,Hurtado-Guerrero, R.,Peregrina, J.M.,Bernardes, G.J.,Corzana, F. (deposition date: 2017-09-02, release date: 2017-12-13, Last modification date: 2024-10-23)

Primary citation

Somovilla, V.J.,Bermejo, I.A.,Albuquerque, I.S.,Martinez-Saez, N.,Castro-Lopez, J.,Garcia-Martin, F.,Companon, I.,Hinou, H.,Nishimura, S.I.,Jimenez-Barbero, J.,Asensio, J.L.,Avenoza, A.,Busto, J.H.,Hurtado-Guerrero, R.,Peregrina, J.M.,Bernardes, G.J.L.,Corzana, F.
The Use of Fluoroproline in MUC1 Antigen Enables Efficient Detection of Antibodies in Patients with Prostate Cancer.
J. Am. Chem. Soc., 139:18255-18261, 2017

PubMed Abstract: A structure-based design of a new generation of tumor-associated glycopeptides with improved affinity against two anti-MUC1 antibodies is described. These unique antigens feature a fluorinated proline residue, such as a (4S)-4-fluoro-l-proline or 4,4-difluoro-l-proline, at the most immunogenic domain. Binding assays using biolayer interferometry reveal 3-fold to 10-fold affinity improvement with respect to the natural (glyco)peptides. According to X-ray crystallography and MD simulations, the fluorinated residues stabilize the antigen-antibody complex by enhancing key CH/π interactions. Interestingly, a notable improvement in detection of cancer-associated anti-MUC1 antibodies from serum of patients with prostate cancer is achieved with the non-natural antigens, which proves that these derivatives can be considered better diagnostic tools than the natural antigen for prostate cancer.

PubMed: 29166012
DOI: 10.1021/jacs.7b09447

Experimental method

X-RAY DIFFRACTION (1.85 Å)