View source for 9ne2


==cryoEM structure of the human OGA-L Catalytic Dimer==
<StructureSection load='9ne2' size='340' side='right'caption='[[9ne2]], [[Resolution|resolution]] 3.63&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[9ne2]] 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=9NE2 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=9NE2 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]] 3.63&#8491;</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=9ne2 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=9ne2 OCA], [https://pdbe.org/9ne2 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=9ne2 RCSB], [https://www.ebi.ac.uk/pdbsum/9ne2 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=9ne2 ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/OGA_HUMAN OGA_HUMAN] Isoform 1: Cleaves GlcNAc but not GalNAc from O-glycosylated proteins. Can use p-nitrophenyl-beta-GlcNAc and 4-methylumbelliferone-GlcNAc as substrates but not p-nitrophenyl-beta-GalNAc or p-nitrophenyl-alpha-GlcNAc (in vitro) (PubMed:11148210). Does not bind acetyl-CoA and does not have histone acetyltransferase activity (PubMed:24088714).<ref>PMID:11148210</ref> <ref>PMID:11788610</ref> <ref>PMID:20673219</ref> <ref>PMID:22365600</ref> <ref>PMID:24088714</ref>   Isoform 3: Cleaves GlcNAc but not GalNAc from O-glycosylated proteins. Can use p-nitrophenyl-beta-GlcNAc as substrate but not p-nitrophenyl-beta-GalNAc or p-nitrophenyl-alpha-GlcNAc (in vitro), but has about six times lower specific activity than isoform 1.<ref>PMID:20673219</ref> 
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
Although thousands of proteins are specifically O-GlcNAc modified, the molecular features recognized by the enzymes of O-GlcNAc cycling (OGT/OGA) remain poorly defined. Here we solved the structure of the long isoform of human OGA (OGA-L) by cryo-electron microscopy (cryo-EM) providing a physiologically relevant platform to study the enzyme. The catalytic-stalk dimer structure was solved to a resolution of 3.63 A, and the locally refined OGA A- and B-chains to 2.98 A and 3.05 A respectively. Intriguingly, the cryo-EM structures also exhibit lower resolution densities associated with the pHAT domains, suggesting substantial flexion of these domains relative to the catalytic-stalk dimer. OGA-L binds to a small subset of the 384 modified histone tails on a commercial histone peptide array. High affinity binding of OGA-L was detected to recombinant DNA-containing mononucleosomes bearing the H3K36(Me3) and H4K(5,8,12,16Ac) modifications. The OGA-L-H3K36(Me3) interaction was further validated by traditional ChIP experiments in MEFs. Thus, OGA-L binds to two modified histone tails of nucleosomes linked to open chromatin, whereas it does not bind to marks associated with repressive chromatin. This model is consistent with OGA-L acting as a 'reader' of histone modifications linked to development, transcriptional activation, transposon silencing, and DNA damage repair.

Human O-GlcNAcase catalytic-stalk dimer anchors flexible histone binding domains.,Nyenhuis SB, Steenackers A, Mukherjee MM, Hinshaw JE, Hanover JA Commun Chem. 2025 Dec 9. doi: 10.1038/s42004-025-01813-7. PMID:41366547<ref>PMID:41366547</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 9ne2" style="background-color:#fffaf0;"></div>
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Hanover JA]]
[[Category: Hinshaw JE]]
[[Category: Nyenhuis SB]]
[[Category: Steenackers A]]