8w4a: Difference between revisions
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The entry | ==membrane proteins== | ||
<StructureSection load='8w4a' size='340' side='right'caption='[[8w4a]], [[Resolution|resolution]] 2.69Å' scene=''> | |||
== Structural highlights == | |||
<table><tr><td colspan='2'>[[8w4a]] 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=8W4A OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=8W4A FirstGlance]. <br> | |||
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">Electron Microscopy, [[Resolution|Resolution]] 2.69Å</td></tr> | |||
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=ACO:ACETYL+COENZYME+*A'>ACO</scene>, <scene name='pdbligand=C14:TETRADECANE'>C14</scene>, <scene name='pdbligand=CLR:CHOLESTEROL'>CLR</scene>, <scene name='pdbligand=D10:DECANE'>D10</scene>, <scene name='pdbligand=D12:DODECANE'>D12</scene>, <scene name='pdbligand=HP6:HEPTANE'>HP6</scene>, <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene>, <scene name='pdbligand=OCT:N-OCTANE'>OCT</scene>, <scene name='pdbligand=R16:HEXADECANE'>R16</scene>, <scene name='pdbligand=UV6:~{N}-[(2~{S},3~{R},4~{R},5~{S},6~{R})-6-(hydroxymethyl)-2-[[(2~{R},4~{R})-4-methyl-2-oxidanyl-3,4-dihydro-2~{H}-chromen-7-yl]oxy]-4,5-bis(oxidanyl)oxan-3-yl]ethanamide'>UV6</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=8w4a FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=8w4a OCA], [https://pdbe.org/8w4a PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=8w4a RCSB], [https://www.ebi.ac.uk/pdbsum/8w4a PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=8w4a ProSAT]</span></td></tr> | |||
</table> | |||
== Disease == | |||
[https://www.uniprot.org/uniprot/HGNAT_HUMAN HGNAT_HUMAN] Retinitis pigmentosa;Sanfilippo syndrome type C. The disease is caused by variants affecting the gene represented in this entry. The disease is caused by variants affecting the gene represented in this entry. | |||
== Function == | |||
[https://www.uniprot.org/uniprot/HGNAT_HUMAN HGNAT_HUMAN] Lysosomal acetyltransferase that acetylates the non-reducing terminal alpha-glucosamine residue of intralysosomal heparin or heparan sulfate, converting it into a substrate for luminal alpha-N-acetyl glucosaminidase.<ref>PMID:16960811</ref> <ref>PMID:17033958</ref> <ref>PMID:19823584</ref> <ref>PMID:20650889</ref> | |||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
Lysosomal transmembrane acetylation of heparan sulfates (HS) is catalyzed by HS acetyl-CoA:alpha-glucosaminide N-acetyltransferase (HGSNAT), whose dysfunction leads to lysosomal storage diseases. The mechanism by which HGSNAT, the sole non-hydrolase enzyme in HS degradation, brings cytosolic acetyl-coenzyme A (Ac-CoA) and lysosomal HS together for N-acyltransferase reactions remains unclear. Here, we present cryogenic-electron microscopy structures of HGSNAT alone, complexed with Ac-CoA and with acetylated products. These structures explain that Ac-CoA binding from the cytosolic side causes dimeric HGSNAT to form a transmembrane tunnel. Within this tunnel, catalytic histidine and asparagine approach the lumen and instigate the transfer of the acetyl group from Ac-CoA to the glucosamine group of HS. Our study unveils a transmembrane acetylation mechanism that may help advance therapeutic strategies targeting lysosomal storage diseases. | |||
Structure and mechanism of lysosome transmembrane acetylation by HGSNAT.,Xu R, Ning Y, Ren F, Gu C, Zhu Z, Pan X, Pshezhetsky AV, Ge J, Yu J Nat Struct Mol Biol. 2024 Oct;31(10):1502-1508. doi: 10.1038/s41594-024-01315-5. , Epub 2024 May 20. PMID:38769387<ref>PMID:38769387</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
[[Category: | </div> | ||
<div class="pdbe-citations 8w4a" style="background-color:#fffaf0;"></div> | |||
== References == | |||
<references/> | |||
__TOC__ | |||
</StructureSection> | |||
[[Category: Homo sapiens]] | |||
[[Category: Large Structures]] | |||
[[Category: Ge JP]] | |||
[[Category: Xu RS]] | |||
[[Category: Yu J]] | |||
