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==Crystal structure of a MUC1-like glycopeptide containing the unnatural L-4-hydroxynorvaline in complex with scFv-SM3== | |||
<StructureSection load='8axh' size='340' side='right'caption='[[8axh]], [[Resolution|resolution]] 1.85Å' scene=''> | |||
== Structural highlights == | |||
<table><tr><td colspan='2'>[[8axh]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] and [https://en.wikipedia.org/wiki/Mus_musculus Mus musculus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=8AXH OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=8AXH 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]] 1.85Å</td></tr> | |||
[[Category: | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=A2G:N-ACETYL-2-DEOXY-2-AMINO-GALACTOSE'>A2G</scene>, <scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene>, <scene name='pdbligand=NH2:AMINO+GROUP'>NH2</scene>, <scene name='pdbligand=VAH:(3R)-3-HYDROXY-L-NORVALINE'>VAH</scene></td></tr> | ||
[[Category: Bermejo | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=8axh FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=8axh OCA], [https://pdbe.org/8axh PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=8axh RCSB], [https://www.ebi.ac.uk/pdbsum/8axh PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=8axh ProSAT]</span></td></tr> | ||
[[Category: Corzana | </table> | ||
[[Category: Hurtado-Guerrero | == Disease == | ||
[https://www.uniprot.org/uniprot/MUC1_HUMAN MUC1_HUMAN] Note=MUC1/CA 15-3 is used as a serological clinical marker of breast cancer to monitor response to breast cancer treatment and disease recurrence (PubMed:20816948). Decreased levels over time may be indicative of a positive response to treatment. Conversely, increased levels may indicate disease progression. At an early stage disease, only 21% of patients exhibit high MUC1/CA 15-3 levels, that is why CA 15-3 is not a useful screening test. Most antibodies target the highly immunodominant core peptide domain of 20 amino acid (APDTRPAPGSTAPPAHGVTS) tandem repeats. Some antibodies recognize glycosylated epitopes. | |||
== Function == | |||
[https://www.uniprot.org/uniprot/MUC1_HUMAN MUC1_HUMAN] The alpha subunit has cell adhesive properties. Can act both as an adhesion and an anti-adhesion protein. May provide a protective layer on epithelial cells against bacterial and enzyme attack.<ref>PMID:9139698</ref> <ref>PMID:11877440</ref> <ref>PMID:14688481</ref> <ref>PMID:15710329</ref> <ref>PMID:16288032</ref> <ref>PMID:15513966</ref> <ref>PMID:17524503</ref> <ref>PMID:17308127</ref> <ref>PMID:16983337</ref> The beta subunit contains a C-terminal domain which is involved in cell signaling, through phosphorylations and protein-protein interactions. Modulates signaling in ERK, SRC and NF-kappa-B pathways. In activated T-cells, influences directly or indirectly the Ras/MAPK pathway. Promotes tumor progression. Regulates TP53-mediated transcription and determines cell fate in the genotoxic stress response. Binds, together with KLF4, the PE21 promoter element of TP53 and represses TP53 activity.<ref>PMID:9139698</ref> <ref>PMID:11877440</ref> <ref>PMID:14688481</ref> <ref>PMID:15710329</ref> <ref>PMID:16288032</ref> <ref>PMID:15513966</ref> <ref>PMID:17524503</ref> <ref>PMID:17308127</ref> <ref>PMID:16983337</ref> | |||
== References == | |||
<references/> | |||
__TOC__ | |||
</StructureSection> | |||
[[Category: Homo sapiens]] | |||
[[Category: Large Structures]] | |||
[[Category: Mus musculus]] | |||
[[Category: Bermejo I]] | |||
[[Category: Corzana F]] | |||
[[Category: Hurtado-Guerrero R]] | |||
Latest revision as of 08:22, 9 August 2023
Crystal structure of a MUC1-like glycopeptide containing the unnatural L-4-hydroxynorvaline in complex with scFv-SM3Crystal structure of a MUC1-like glycopeptide containing the unnatural L-4-hydroxynorvaline in complex with scFv-SM3
Structural highlights
DiseaseMUC1_HUMAN Note=MUC1/CA 15-3 is used as a serological clinical marker of breast cancer to monitor response to breast cancer treatment and disease recurrence (PubMed:20816948). Decreased levels over time may be indicative of a positive response to treatment. Conversely, increased levels may indicate disease progression. At an early stage disease, only 21% of patients exhibit high MUC1/CA 15-3 levels, that is why CA 15-3 is not a useful screening test. Most antibodies target the highly immunodominant core peptide domain of 20 amino acid (APDTRPAPGSTAPPAHGVTS) tandem repeats. Some antibodies recognize glycosylated epitopes. FunctionMUC1_HUMAN The alpha subunit has cell adhesive properties. Can act both as an adhesion and an anti-adhesion protein. May provide a protective layer on epithelial cells against bacterial and enzyme attack.[1] [2] [3] [4] [5] [6] [7] [8] [9] The beta subunit contains a C-terminal domain which is involved in cell signaling, through phosphorylations and protein-protein interactions. Modulates signaling in ERK, SRC and NF-kappa-B pathways. In activated T-cells, influences directly or indirectly the Ras/MAPK pathway. Promotes tumor progression. Regulates TP53-mediated transcription and determines cell fate in the genotoxic stress response. Binds, together with KLF4, the PE21 promoter element of TP53 and represses TP53 activity.[10] [11] [12] [13] [14] [15] [16] [17] [18] References
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