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==Crystal Structures of beta-1,4-N-Acetylglucosaminyltransferase 2 (POMGNT2): Structural Basis for Inherited Muscular Dystrophies==
<StructureSection load='6xfi' size='340' side='right'caption='[[6xfi]], [[Resolution|resolution]] 2.00&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6XFI OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6XFI 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&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene>, <scene name='pdbligand=PO4:PHOSPHATE+ION'>PO4</scene>, <scene name='pdbligand=UDP:URIDINE-5-DIPHOSPHATE'>UDP</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=6xfi FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6xfi OCA], [https://pdbe.org/6xfi PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6xfi RCSB], [https://www.ebi.ac.uk/pdbsum/6xfi PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6xfi ProSAT]</span></td></tr>
</table>
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== Publication Abstract from PubMed ==
The canonical O-mannosylation pathway in humans is essential for the functional glycosylation of alpha-dystroglycan. Disruption of this post-translational modification pathway leads to congenital muscular dystrophies. The first committed step in the construction of a functional matriglycan structure involves the post-translational modification of alpha-dystroglycan. This is essential for binding extracellular matrix proteins and arenaviruses, and is catalyzed by beta-1,4-N-acetylglucosaminyltransferase 2 (POMGNT2). While another glycosyl transferase, beta-1,4-N-acetylglucosaminyltransferase 1 (POMGNT1), has been shown to be promiscuous in extending O-mannosylated sites, POMGNT2 has been shown to display significant primary amino-acid selectivity near the site of O-mannosylation. Moreover, several single point mutations in POMGNT2 have been identified in patients with assorted dystroglycanopathies such as Walker-Warburg syndrome and limb girdle muscular dystrophy. To gain insight into POMGNT2 function in humans, the enzyme was expressed as a soluble, secreted fusion protein by transient infection of HEK293 suspension cultures. Here, crystal structures of POMGNT2 (amino-acid residues 25-580) with and without UDP bound are reported. Consistent with a novel fold and a unique domain organization, no molecular-replacement model was available and phases were obtained through crystallization of a selenomethionine variant of the enzyme in the same space group. Tetragonal (space group P4212; unit-cell parameters a = b = 129.8, c = 81.6 A, alpha = gamma = beta = 90 degrees ) crystals with UDP bound diffracted to 1.98 A resolution and contained a single monomer in the asymmetric unit. Orthorhombic (space group P212121; unit-cell parameters a = 142.3, b = 153.9, c = 187.4 A, alpha = gamma = beta = 90 degrees ) crystals were also obtained; they diffracted to 2.57 A resolution and contained four monomers with differential glycosylation patterns and conformations. These structures provide the first rational basis for an explanation of the loss-of-function mutations and offer significant insights into the mechanics of this important human enzyme.

Crystal structures of beta-1,4-N-acetylglucosaminyltransferase 2: structural basis for inherited muscular dystrophies.,Yang JY, Halmo SM, Praissman J, Chapla D, Singh D, Wells L, Moremen KW, Lanzilotta WN Acta Crystallogr D Struct Biol. 2021 Apr 1;77(Pt 4):486-495. doi:, 10.1107/S2059798321001261. Epub 2021 Mar 30. PMID:33825709<ref>PMID:33825709</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Large Structures]]
[[Category: Halmo SM]]
[[Category: Lanzilotta WN]]
[[Category: Moremen KW]]
[[Category: Wells L]]
[[Category: Yeh J]]