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5vvx

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Revision as of 08:45, 30 September 2020

Structural Investigations of the Substrate Specificity of Human O-GlcNAcase

Structural highlights

5vvx is a 4 chain structure with sequence from Human. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Ligands:
Related:	5vvo, 5vvt, 5vvu, 5vvv
Gene:	MGEA5, HEXC, KIAA0679, MEA5 (HUMAN)
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

The O-linked beta-N-acetyl glucosamine (O-GlcNAc) modification dynamically regulates the functions of numerous proteins. A single human enzyme O-linked beta-N-acetyl glucosaminase (O-GlcNAcase or OGA) hydrolyzes this modification. To date, it remains largely unknown how OGA recognizes various substrates. Here we report the structures of OGA in complex with each of four distinct glycopeptide substrates that contain a single O-GlcNAc modification on a serine or threonine residue. Intriguingly, these glycopeptides bind in a bidirectional yet conserved conformation within the substrate-binding cleft of OGA. This study provides fundamental insights into a general principle that confers the substrate binding adaptability and specificity to OGA in O-GlcNAc regulation.O-linked beta-N-acetyl glucosamine (O-GlcNAc) is an important protein modification that is hydrolyzed by O-GlcNAcase (OGA). Here the authors give insights into OGA substrate recognition by presenting four human OGA structures complexed with glycopeptide substrates containing a single O-GlcNAc modification on either a serine or threonine.

Structural insights into the substrate binding adaptability and specificity of human O-GlcNAcase.,Li B, Li H, Hu CW, Jiang J Nat Commun. 2017 Sep 22;8(1):666. doi: 10.1038/s41467-017-00865-1. PMID:28939839^[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, Hu CW, Jiang J. Structural insights into the substrate binding adaptability and specificity of human O-GlcNAcase. Nat Commun. 2017 Sep 22;8(1):666. doi: 10.1038/s41467-017-00865-1. PMID:28939839 doi:http://dx.doi.org/10.1038/s41467-017-00865-1

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

Proteopedia Page Contributors and Editors (what is this?)

OCA

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

@@ Line 1: / Line 1: @@
 ==Structural Investigations of the Substrate Specificity of Human O-GlcNAcase==
-<StructureSection load='5vvx' size='340' side='right' caption='[[5vvx]], [[Resolution|resolution]] 2.90&Aring;' scene=''>
+<StructureSection load='5vvx' size='340' side='right'caption='[[5vvx]], [[Resolution|resolution]] 2.90&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[5vvx]] is a 4 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5VVX OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5VVX FirstGlance]. <br>
+<table><tr><td colspan='2'>[[5vvx]] is a 4 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5VVX OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=5VVX FirstGlance]. <br>
-</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene></td></tr>
+</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='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[5vvo|5vvo]], [[5vvt|5vvt]], [[5vvu|5vvu]], [[5vvv|5vvv]]</td></tr>
-<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5vvx FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5vvx OCA], [http://pdbe.org/5vvx PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5vvx RCSB], [http://www.ebi.ac.uk/pdbsum/5vvx PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5vvx ProSAT]</span></td></tr>
+<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">MGEA5, HEXC, KIAA0679, MEA5 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr>
+<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://proteopedia.org/fgij/fg.htm?mol=5vvx FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5vvx OCA], [http://pdbe.org/5vvx PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5vvx RCSB], [http://www.ebi.ac.uk/pdbsum/5vvx PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5vvx ProSAT]</span></td></tr>
 </table>
 == Function ==
@@ Line 23: / Line 24: @@
 __TOC__
 </StructureSection>
+[[Category: Human]]
+[[Category: Large Structures]]
 [[Category: Hu, C W]]
 [[Category: Jiang, J]]

5vvx

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Revision as of 08:45, 30 September 2020

Structural Investigations of the Substrate Specificity of Human O-GlcNAcase

Structural highlights

Function

Publication Abstract from PubMed

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

Views

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