View source for 5gz9


==Crystal structure of catalytic domain of Protein O-mannosyl Kinase in complexes with AMP-PNP, Magnesium ions and glycopeptide==
<StructureSection load='5gz9' size='340' side='right'caption='[[5gz9]], [[Resolution|resolution]] 2.40&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[5gz9]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Mus_musculus Mus musculus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5GZ9 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5GZ9 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]] 2.4&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=ANP:PHOSPHOAMINOPHOSPHONIC+ACID-ADENYLATE+ESTER'>ANP</scene>, <scene name='pdbligand=MAN:ALPHA-D-MANNOSE'>MAN</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</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=5gz9 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5gz9 OCA], [https://pdbe.org/5gz9 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5gz9 RCSB], [https://www.ebi.ac.uk/pdbsum/5gz9 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5gz9 ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/SG196_MOUSE SG196_MOUSE] Protein O-mannose kinase that specifically mediates phosphorylation at the 6-position of an O-mannose of the trisaccharide (N-acetylgalactosamine (GalNAc)-beta-1,3-N-acetylglucosamine (GlcNAc)-beta-1,4-mannose) to generate phosphorylated O-mannosyl trisaccharide (N-acetylgalactosamine-beta-1,3-N-acetylglucosamine-beta-1,4-(phosphate-6-)mannose). Phosphorylated O-mannosyl trisaccharide is a carbohydrate structure present in alpha-dystroglycan (DAG1), which is required for binding laminin G-like domain-containing extracellular proteins with high affinity. Only shows kinase activity when the GalNAc-beta-3-GlcNAc-beta-terminus is linked to the 4-position of O-mannose, suggesting that this disaccharide serves as the substrate recognition motif (By similarity).
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== Publication Abstract from PubMed ==
Orchestration of the multiple enzymes engaged in O-mannose glycan synthesis provides a matriglycan on alpha-dystroglycan (alpha-DG) which attracts extracellular matrix (ECM) proteins such as laminin. Aberrant O-mannosylation of alpha-DG leads to severe congenital muscular dystrophies due to detachment of ECM proteins from the basal membrane. Phosphorylation at C6-position of O-mannose catalyzed by protein O-mannosyl kinase (POMK) is a crucial step in the biosynthetic pathway of O-mannose glycan. Several mis-sense mutations of the POMK catalytic domain are known to cause a severe congenital muscular dystrophy, Walker-Warburg syndrome. Due to the low sequence similarity with other typical kinases, structure-activity relationships of this enzyme remain unclear. Here, we report the crystal structures of the POMK catalytic domain in the absence and presence of an ATP analogue and O-mannosylated glycopeptide. The POMK catalytic domain shows a typical protein kinase fold consisting of N- and C-lobes. Mannose residue binds to POMK mainly via the hydroxyl group at C2-position, differentiating from other monosaccharide residues. Intriguingly, the two amino acid residues K92 and D228, interacting with the triphosphate group of ATP, are donated from atypical positions in the primary structure. Mutations in this protein causing muscular dystrophies can now be rationalized.

3D structural analysis of protein O-mannosyl kinase, POMK, a causative gene product of dystroglycanopathy.,Nagae M, Mishra SK, Neyazaki M, Oi R, Ikeda A, Matsugaki N, Akashi S, Manya H, Mizuno M, Yagi H, Kato K, Senda T, Endo T, Nogi T, Yamaguchi Y Genes Cells. 2017 Mar 2. doi: 10.1111/gtc.12480. PMID:28251761<ref>PMID:28251761</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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<div class="pdbe-citations 5gz9" style="background-color:#fffaf0;"></div>
== References ==
<references/>
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</StructureSection>
[[Category: Large Structures]]
[[Category: Mus musculus]]
[[Category: Nagae M]]
[[Category: Yamaguchi Y]]