7s06

<table><tr><td colspan='2'>[[7s06]] is a 2 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7S06 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7S06 FirstGlance]. <br>

</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></td></tr>

<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[https://en.wikipedia.org/wiki/UDP-N-acetylglucosamine--lysosomal-enzyme_N-acetylglucosaminephosphotransferase UDP-N-acetylglucosamine--lysosomal-enzyme N-acetylglucosaminephosphotransferase], with EC number [https://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.8.17 2.7.8.17] </span></td></tr>

== Disease ==

[[https://www.uniprot.org/uniprot/GNPTA_HUMAN GNPTA_HUMAN]] Mucolipidosis type 2;Mucolipidosis type 3. The disease is caused by mutations affecting the gene represented in this entry. The disease is caused by mutations affecting the gene represented in this entry. Defects in GNPTAB have been suggested to play a role in susceptibility to persistent stuttering. Stuttering is a common speech disorder characterized by repetitions, prolongations, and interruptions in the flow of speech.<ref>PMID:20147709</ref>

== Function ==

[[https://www.uniprot.org/uniprot/GNPTA_HUMAN GNPTA_HUMAN]] Catalyzes the formation of mannose 6-phosphate (M6P) markers on high mannose type oligosaccharides in the Golgi apparatus. M6P residues are required to bind to the M6P receptors (MPR), which mediate the vesicular transport of lysosomal enzymes to the endosomal/prelysosomal compartment.<ref>PMID:19955174</ref> <ref>PMID:23733939</ref>

<div style="background-color:#fffaf0;">

== Publication Abstract from PubMed ==

Vertebrates use the mannose 6-phosphate (M6P)-recognition system to deliver lysosomal hydrolases to lysosomes. Key to this pathway is N-acetylglucosamine (GlcNAc)-1-phosphotransferase (PTase) that selectively adds GlcNAc-phosphate (P) to mannose residues of hydrolases. Human PTase is an alpha2beta2gamma2 heterohexamer with a catalytic core and several peripheral domains that recognize and bind substrates. Here we report a cryo-EM structure of the catalytic core of human PTase and the identification of a hockey stick-like motif that controls activation of the enzyme. Movement of this motif out of the catalytic pocket is associated with a rearrangement of part of the peripheral domains that unblocks hydrolase glycan access to the catalytic site, thereby activating PTase. We propose that PTase fluctuates between inactive and active states in solution, and selective substrate binding of a lysosomal hydrolase through its protein-binding determinant to PTase locks the enzyme in the active state to permit glycan phosphorylation. This mechanism would help ensure that only N-linked glycans of lysosomal enzymes are phosphorylated.

 

== References ==

[[Category: Li, H]]

[[Category: Transferase]]