View source for 9f1i


==Crystal structure of a first-in-class antibody for alpha-1,6-fucosylated prostate-specific antigen, target bound==
<StructureSection load='9f1i' size='340' side='right'caption='[[9f1i]], [[Resolution|resolution]] 1.38&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[9f1i]] is a 6 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] and [https://en.wikipedia.org/wiki/Oryctolagus_cuniculus Oryctolagus cuniculus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=9F1I OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=9F1I FirstGlance]. <br>
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.38&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene>, <scene name='pdbligand=FUC:ALPHA-L-FUCOSE'>FUC</scene>, <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene>, <scene name='pdbligand=PCA:PYROGLUTAMIC+ACID'>PCA</scene>, <scene name='pdbligand=PFX:(2S)-1-({2-[2-(CARBOXYMETHOXY)ETHOXY]ETHYL}AMINO)-1-OXO-3-(4-PHOSPHONOPHENYL)PROPAN-2-AMINIUM'>PFX</scene></td></tr>
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=9f1i FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=9f1i OCA], [https://pdbe.org/9f1i PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=9f1i RCSB], [https://www.ebi.ac.uk/pdbsum/9f1i PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=9f1i ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/Q8NCW4_HUMAN Q8NCW4_HUMAN] 
<div style="background-color:#fffaf0;">
== 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<ref>PMID:39020051</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 9f1i" style="background-color:#fffaf0;"></div>
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Oryctolagus cuniculus]]
[[Category: Halldorsson S]]