9f18

Crystal structure of a first-in-class antibody for alpha-1,6-fucosylated prostate-specific antigen

spinqualitylabelsall models 9f18, resolution 2.52Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 9f18 is a 4 chain structure with sequence from Oryctolagus cuniculus. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 2.52Å Ligands: PCA Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Publication Abstract from PubMed Prostate-specific antigen (PSA) levels are widely used to screen for prostate cancer, yet the test has poor sensitivity, specificity and predictive value, which leads to overdiagnosis and overtreatment. Alterations in the glycosylation status of PSA, including fucosylation, may offer scope for an improved biomarker. We sought to generate a monoclonal antibody (mAb) targeting alpha-1,6-fucosylated PSA (fuc-PSA) and to develop a tissue-based immunological assay for fuc-PSA detection. Immunogens representing fuc-PSA were used for immunisation and resultant mAbs were extensively characterised. The mAbs reacted specifically with fuc-PSA-specific glycopeptide, but not with aglycosylated PSA or glycan without the PSA peptide. Reactivity was confirmed using high-throughput surface plasmon resonance spectroscopy. X-ray crystallography investigations showed that the mAbs bound to an alpha-helical form of the peptide, whereas the native PSA epitope is linear. Protein unfolding was required for detection of fuc-PSA in patient samples. Peptide inhibition of fuc-PSA mAbs was observed with positive screening reagents, and target epitope specificity was observed in formalin-fixed, paraffin-embedded tissue samples. This research introduces a well-characterised, first-in-class antibody targeting fuc-PSA and presents the first crystal structure of an antibody demonstrating glycosylation-specific binding to a peptide. Development of a first-in-class antibody and a specific assay for alpha-1,6-fucosylated prostate-specific antigen.,Halldorsson S, Hillringhaus L, Hojer C, Muranyi A, Schraeml M, Lange MS, Tabares G Sci Rep. 2024 Jul 17;14(1):16512. doi: 10.1038/s41598-024-67545-1. PMID:39020051 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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