5un9

From Proteopedia

(Difference between revisions)

Current revision

The crystal structure of human O-GlcNAcase in complex with Thiamet-G

Structural highlights

5un9 is a 2 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:	X-ray diffraction, Resolution 2.5Å
Ligands:
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

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).^[1] ^[2] ^[3] ^[4] ^[5] 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.^[6]

Publication Abstract from PubMed

Human O-GlcNAcase (hOGA) is the unique enzyme responsible for the hydrolysis of the O-linked beta-N-acetyl glucosamine (O-GlcNAc) modification, an essential protein glycosylation event that modulates the function of numerous cellular proteins in response to nutrients and stress. Here we report crystal structures of a truncated hOGA, which comprises the catalytic and stalk domains, in apo form, in complex with an inhibitor, and in complex with a glycopeptide substrate. We found that hOGA forms an unusual arm-in-arm homodimer in which the catalytic domain of one monomer is covered by the stalk domain of the sister monomer to create a substrate-binding cleft. Notably, the residues on the cleft surface afford extensive interactions with the peptide substrate in a recognition mode that is distinct from that of its bacterial homologs. These structures represent the first model of eukaryotic enzymes in the glycoside hydrolase 84 (GH84) family and provide a crucial starting point for understanding the substrate specificity of hOGA, which regulates a broad range of biological and pathological processes.

Structures of human O-GlcNAcase and its complexes reveal a new substrate recognition mode.,Li B, Li H, Lu L, Jiang J Nat Struct Mol Biol. 2017 Mar 20. doi: 10.1038/nsmb.3390. PMID:28319083^[7]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

References

↑ Gao Y, Wells L, Comer FI, Parker GJ, Hart GW. Dynamic O-glycosylation of nuclear and cytosolic proteins: cloning and characterization of a neutral, cytosolic beta-N-acetylglucosaminidase from human brain. J Biol Chem. 2001 Mar 30;276(13):9838-45. Epub 2001 Jan 8. PMID:11148210 doi:http://dx.doi.org/10.1074/jbc.M010420200
↑ Wells L, Gao Y, Mahoney JA, Vosseller K, Chen C, Rosen A, Hart GW. Dynamic O-glycosylation of nuclear and cytosolic proteins: further characterization of the nucleocytoplasmic beta-N-acetylglucosaminidase, O-GlcNAcase. J Biol Chem. 2002 Jan 18;277(3):1755-61. PMID:11788610
↑ Li J, Huang CL, Zhang LW, Lin L, Li ZH, Zhang FW, Wang P. Isoforms of human O-GlcNAcase show distinct catalytic efficiencies. Biochemistry (Mosc). 2010 Jul;75(7):938-43. PMID:20673219
↑ Schimpl M, Borodkin VS, Gray LJ, van Aalten DM. Synergy of Peptide and Sugar in O-GlcNAcase Substrate Recognition. Chem Biol. 2012 Feb 24;19(2):173-8. PMID:22365600 doi:10.1016/j.chembiol.2012.01.011
↑ Rao FV, Schuttelkopf AW, Dorfmueller HC, Ferenbach AT, Navratilova I, van Aalten DM. Structure of a bacterial putative acetyltransferase defines the fold of the human O-GlcNAcase C-terminal domain. Open Biol. 2013 Oct 2;3(10):130021. PMID:24088714 doi:http://dx.doi.org/10.1098/rsob.130021
↑ Li J, Huang CL, Zhang LW, Lin L, Li ZH, Zhang FW, Wang P. Isoforms of human O-GlcNAcase show distinct catalytic efficiencies. Biochemistry (Mosc). 2010 Jul;75(7):938-43. PMID:20673219
↑ Li B, Li H, Lu L, Jiang J. Structures of human O-GlcNAcase and its complexes reveal a new substrate recognition mode. Nat Struct Mol Biol. 2017 Mar 20. doi: 10.1038/nsmb.3390. PMID:28319083 doi:http://dx.doi.org/10.1038/nsmb.3390

1 Structural highlights
2 Function
3 Publication Abstract from PubMed
4 See Also
5 References

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/5un9"

Categories: Homo sapiens | Large Structures | Jiang J | Li B

@@ Line 1: / Line 1: @@
-'''Unreleased structure'''
-The entry 5un9 is ON HOLD  until Paper Publication
+==The crystal structure of human O-GlcNAcase in complex with Thiamet-G==
+<StructureSection load='5un9' size='340' side='right'caption='[[5un9]], [[Resolution|resolution]] 2.50&Aring;' scene=''>
+== Structural highlights ==
+<table><tr><td colspan='2'>[[5un9]] 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=5UN9 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5UN9 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]] 2.5&#8491;</td></tr>
+<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=NHT:(3AR,5R,6S,7R,7AR)-2-(ETHYLAMINO)-5-(HYDROXYMETHYL)-5,6,7,7A-TETRAHYDRO-3AH-PYRANO[3,2-D][1,3]THIAZOLE-6,7-DIOL'>NHT</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=5un9 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5un9 OCA], [https://pdbe.org/5un9 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5un9 RCSB], [https://www.ebi.ac.uk/pdbsum/5un9 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5un9 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 ==
+Human O-GlcNAcase (hOGA) is the unique enzyme responsible for the hydrolysis of the O-linked beta-N-acetyl glucosamine (O-GlcNAc) modification, an essential protein glycosylation event that modulates the function of numerous cellular proteins in response to nutrients and stress. Here we report crystal structures of a truncated hOGA, which comprises the catalytic and stalk domains, in apo form, in complex with an inhibitor, and in complex with a glycopeptide substrate. We found that hOGA forms an unusual arm-in-arm homodimer in which the catalytic domain of one monomer is covered by the stalk domain of the sister monomer to create a substrate-binding cleft. Notably, the residues on the cleft surface afford extensive interactions with the peptide substrate in a recognition mode that is distinct from that of its bacterial homologs. These structures represent the first model of eukaryotic enzymes in the glycoside hydrolase 84 (GH84) family and provide a crucial starting point for understanding the substrate specificity of hOGA, which regulates a broad range of biological and pathological processes.
-Authors: Li, B., Jiang, J.
+Structures of human O-GlcNAcase and its complexes reveal a new substrate recognition mode.,Li B, Li H, Lu L, Jiang J Nat Struct Mol Biol. 2017 Mar 20. doi: 10.1038/nsmb.3390. PMID:28319083<ref>PMID:28319083</ref>
-Description: The crystal structure of human O-GlcNAcase in complex with Thiamet-G
+From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
-[[Category: Unreleased Structures]]
+</div>
-[[Category: Jiang, J]]
+<div class="pdbe-citations 5un9" style="background-color:#fffaf0;"></div>
-[[Category: Li, B]]
+==See Also==
+*[[O-GlcNAcase|O-GlcNAcase]]
+== References ==
+<references/>
+__TOC__
+</StructureSection>
+[[Category: Homo sapiens]]
+[[Category: Large Structures]]
+[[Category: Jiang J]]
+[[Category: Li B]]

5un9

From Proteopedia

Current revision

The crystal structure of human O-GlcNAcase in complex with Thiamet-G

Structural highlights

Function

Publication Abstract from PubMed

See Also

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

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