5m7u

From Proteopedia

(Difference between revisions)

Current revision

Structure of human O-GlcNAc hydrolase with new iminocyclitol type inhibitor

Structural highlights

5m7u 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 2.3Å
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

O-GlcNAc hydrolase (OGA) removes O-linked N-acetylglucosamine (O-GlcNAc) from a myriad of nucleocytoplasmic proteins. Through co-expression and assembly of OGA fragments, we determined the three-dimensional structure of human OGA, revealing an unusual helix-exchanged dimer that lays a structural foundation for an improved understanding of substrate recognition and regulation of OGA. Structures of OGA in complex with a series of inhibitors define a precise blueprint for the design of inhibitors that have clinical value.

Structural and functional insight into human O-GlcNAcase.,Roth C, Chan S, Offen WA, Hemsworth GR, Willems LI, King DT, Varghese V, Britton R, Vocadlo DJ, Davies GJ Nat Chem Biol. 2017 Mar 27. doi: 10.1038/nchembio.2358. PMID:28346405^[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
↑ Roth C, Chan S, Offen WA, Hemsworth GR, Willems LI, King DT, Varghese V, Britton R, Vocadlo DJ, Davies GJ. Structural and functional insight into human O-GlcNAcase. Nat Chem Biol. 2017 Mar 27. doi: 10.1038/nchembio.2358. PMID:28346405 doi:http://dx.doi.org/10.1038/nchembio.2358

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/5m7u"

@@ Line 1: / Line 1: @@
-'''Unreleased structure'''
-The entry 5m7u is ON HOLD  until Paper Publication
+==Structure of human O-GlcNAc hydrolase with new iminocyclitol type inhibitor==
+<StructureSection load='5m7u' size='340' side='right'caption='[[5m7u]], [[Resolution|resolution]] 2.30&Aring;' scene=''>
+== Structural highlights ==
+<table><tr><td colspan='2'>[[5m7u]] 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=5M7U OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5M7U 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]] 2.3&#8491;</td></tr>
+<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=XHA:2-[(2~{R},3~{S},4~{R},5~{R})-5-(HYDROXYMETHYL)-3,4-BIS(OXIDANYL)-1-[3-[3-(TRIFLUOROMETHYL)PHENYL]PROPYL]PYRROLIDIN-2-YL]-~{N}-METHYL-ETHANAMIDE'>XHA</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=5m7u FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5m7u OCA], [https://pdbe.org/5m7u PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5m7u RCSB], [https://www.ebi.ac.uk/pdbsum/5m7u PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5m7u 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 ==
+O-GlcNAc hydrolase (OGA) removes O-linked N-acetylglucosamine (O-GlcNAc) from a myriad of nucleocytoplasmic proteins. Through co-expression and assembly of OGA fragments, we determined the three-dimensional structure of human OGA, revealing an unusual helix-exchanged dimer that lays a structural foundation for an improved understanding of substrate recognition and regulation of OGA. Structures of OGA in complex with a series of inhibitors define a precise blueprint for the design of inhibitors that have clinical value.
-Authors:
+Structural and functional insight into human O-GlcNAcase.,Roth C, Chan S, Offen WA, Hemsworth GR, Willems LI, King DT, Varghese V, Britton R, Vocadlo DJ, Davies GJ Nat Chem Biol. 2017 Mar 27. doi: 10.1038/nchembio.2358. PMID:28346405<ref>PMID:28346405</ref>
-Description:
+From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
-[[Category: Unreleased Structures]]
+</div>
+<div class="pdbe-citations 5m7u" style="background-color:#fffaf0;"></div>
+==See Also==
+*[[O-GlcNAcase|O-GlcNAcase]]
+== References ==
+<references/>
+__TOC__
+</StructureSection>
+[[Category: Homo sapiens]]
+[[Category: Large Structures]]
+[[Category: Britton R]]
+[[Category: Chan S]]
+[[Category: Davies GJ]]
+[[Category: Hemsworth GR]]
+[[Category: King D]]
+[[Category: Offen WA]]
+[[Category: Roth C]]
+[[Category: Varghese V]]
+[[Category: Vocadlo DJ]]
+[[Category: Willems LI]]

5m7u

From Proteopedia

Current revision

Structure of human O-GlcNAc hydrolase with new iminocyclitol type inhibitor

Structural highlights

Function

Publication Abstract from PubMed

See Also

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

Views

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