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| | <StructureSection load='5ajn' size='340' side='right'caption='[[5ajn]], [[Resolution|resolution]] 1.67Å' scene=''> | | <StructureSection load='5ajn' size='340' side='right'caption='[[5ajn]], [[Resolution|resolution]] 1.67Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[5ajn]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5AJN OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5AJN FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[5ajn]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5AJN OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5AJN FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><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=SO4:SULFATE+ION'>SO4</scene></td></tr> | + | </td></tr><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=SO4:SULFATE+ION'>SO4</scene></td></tr> |
| - | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[5ajo|5ajo]], [[5ajp|5ajp]]</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=5ajn FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5ajn OCA], [https://pdbe.org/5ajn PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5ajn RCSB], [https://www.ebi.ac.uk/pdbsum/5ajn PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5ajn ProSAT]</span></td></tr> |
| - | <tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Polypeptide_N-acetylgalactosaminyltransferase Polypeptide N-acetylgalactosaminyltransferase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.4.1.41 2.4.1.41] </span></td></tr>
| + | |
| - | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5ajn FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5ajn OCA], [http://pdbe.org/5ajn PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5ajn RCSB], [http://www.ebi.ac.uk/pdbsum/5ajn PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5ajn ProSAT]</span></td></tr> | + | |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/GALT2_HUMAN GALT2_HUMAN]] Catalyzes the initial reaction in O-linked oligosaccharide biosynthesis, the transfer of an N-acetyl-D-galactosamine residue to a serine or threonine residue on the protein receptor. Has a broad spectrum of substrates for peptides such as EA2, Muc5AC, Muc1a, Muc1b. Probably involved in O-linked glycosylation of the immunoglobulin A1 (IgA1) hinge region.<ref>PMID:9295285</ref> <ref>PMID:12438318</ref> | + | [https://www.uniprot.org/uniprot/MUC5A_HUMAN MUC5A_HUMAN] Gel-forming glycoprotein of gastric and respiratory tract epithelia that protects the mucosa from infection and chemical damage by binding to inhaled microorganisms and particles that are subsequently removed by the mucociliary system (PubMed:14535999, PubMed:14718370). Interacts with H.pylori in the gastric epithelium, Barrett's esophagus as well as in gastric metaplasia of the duodenum (GMD) (PubMed:14535999).<ref>PMID:14535999</ref> <ref>PMID:14535999</ref> <ref>PMID:14718370</ref> |
| | <div style="background-color:#fffaf0;"> | | <div style="background-color:#fffaf0;"> |
| | == Publication Abstract from PubMed == | | == Publication Abstract from PubMed == |
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| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Human]] | + | [[Category: Homo sapiens]] |
| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| - | [[Category: Polypeptide N-acetylgalactosaminyltransferase]]
| + | [[Category: Bernado P]] |
| - | [[Category: Bernado, P]] | + | [[Category: Bernardes GJL]] |
| - | [[Category: Bernardes, G J.L]] | + | [[Category: Bruscolini P]] |
| - | [[Category: Bruscolini, P]] | + | [[Category: Clausen H]] |
| - | [[Category: Clausen, H]] | + | [[Category: Companon I]] |
| - | [[Category: Companon, I]] | + | [[Category: Corzana F]] |
| - | [[Category: Corzana, F]] | + | [[Category: Hurtado-Guerrero R]] |
| - | [[Category: Hurtado-Guerrero, R]] | + | [[Category: Iglesias-Fernandez J]] |
| - | [[Category: Iglesias-Fernandez, J]] | + | [[Category: Kong Y]] |
| - | [[Category: Kong, Y]] | + | [[Category: Lira-Navarrete E]] |
| - | [[Category: Lira-Navarrete, E]] | + | [[Category: Lostao A]] |
| - | [[Category: Lostao, A]] | + | [[Category: Pallares MC]] |
| - | [[Category: Pallares, M C]] | + | [[Category: Peregrina JM]] |
| - | [[Category: Peregrina, J M]] | + | [[Category: Rovira C]] |
| - | [[Category: Rovira, C]] | + | [[Category: DelasRivas M]] |
| - | [[Category: DelasRivas, M]] | + | |
| - | [[Category: Active form]]
| + | |
| - | [[Category: Afm]]
| + | |
| - | [[Category: Coarse-grained model]]
| + | |
| - | [[Category: Compact form]]
| + | |
| - | [[Category: Extended form]]
| + | |
| - | [[Category: Glycopeptide]]
| + | |
| - | [[Category: Inactive form]]
| + | |
| - | [[Category: Lectin domain]]
| + | |
| - | [[Category: Sax]]
| + | |
| - | [[Category: Transferase]]
| + | |
| Structural highlights
Function
MUC5A_HUMAN Gel-forming glycoprotein of gastric and respiratory tract epithelia that protects the mucosa from infection and chemical damage by binding to inhaled microorganisms and particles that are subsequently removed by the mucociliary system (PubMed:14535999, PubMed:14718370). Interacts with H.pylori in the gastric epithelium, Barrett's esophagus as well as in gastric metaplasia of the duodenum (GMD) (PubMed:14535999).[1] [2] [3]
Publication Abstract from PubMed
Protein O-glycosylation is controlled by polypeptide GalNAc-transferases (GalNAc-Ts) that uniquely feature both a catalytic and lectin domain. The underlying molecular basis of how the lectin domains of GalNAc-Ts contribute to glycopeptide specificity and catalysis remains unclear. Here we present the first crystal structures of complexes of GalNAc-T2 with glycopeptides that together with enhanced sampling molecular dynamics simulations demonstrate a cooperative mechanism by which the lectin domain enables free acceptor sites binding of glycopeptides into the catalytic domain. Atomic force microscopy and small-angle X-ray scattering experiments further reveal a dynamic conformational landscape of GalNAc-T2 and a prominent role of compact structures that are both required for efficient catalysis. Our model indicates that the activity profile of GalNAc-T2 is dictated by conformational heterogeneity and relies on a flexible linker located between the catalytic and the lectin domains. Our results also shed light on how GalNAc-Ts generate dense decoration of proteins with O-glycans.
Dynamic interplay between catalytic and lectin domains of GalNAc-transferases modulates protein O-glycosylation.,Lira-Navarrete E, de Las Rivas M, Companon I, Pallares MC, Kong Y, Iglesias-Fernandez J, Bernardes GJ, Peregrina JM, Rovira C, Bernado P, Bruscolini P, Clausen H, Lostao A, Corzana F, Hurtado-Guerrero R Nat Commun. 2015 May 5;6:6937. doi: 10.1038/ncomms7937. PMID:25939779[4]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Van de Bovenkamp JH, Mahdavi J, Korteland-Van Male AM, Büller HA, Einerhand AW, Borén T, Dekker J. The MUC5AC glycoprotein is the primary receptor for Helicobacter pylori in the human stomach. Helicobacter. 2003;8(5):521-32. PMID:14535999 doi:10.1046/j.1523-5378.2003.00173.x
- ↑ Van de Bovenkamp JH, Mahdavi J, Korteland-Van Male AM, Büller HA, Einerhand AW, Borén T, Dekker J. The MUC5AC glycoprotein is the primary receptor for Helicobacter pylori in the human stomach. Helicobacter. 2003;8(5):521-32. PMID:14535999 doi:10.1046/j.1523-5378.2003.00173.x
- ↑ Perez-Vilar J, Randell SH, Boucher RC. C-Mannosylation of MUC5AC and MUC5B Cys subdomains. Glycobiology. 2004 Apr;14(4):325-37. PMID:14718370 doi:10.1093/glycob/cwh041
- ↑ Lira-Navarrete E, de Las Rivas M, Companon I, Pallares MC, Kong Y, Iglesias-Fernandez J, Bernardes GJ, Peregrina JM, Rovira C, Bernado P, Bruscolini P, Clausen H, Lostao A, Corzana F, Hurtado-Guerrero R. Dynamic interplay between catalytic and lectin domains of GalNAc-transferases modulates protein O-glycosylation. Nat Commun. 2015 May 5;6:6937. doi: 10.1038/ncomms7937. PMID:25939779 doi:http://dx.doi.org/10.1038/ncomms7937
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