7kzg - Revision history

OCA at 15:35, 18 October 2023

2023-10-18T15:35:11Z

←Older revision		Revision as of 15:35, 18 October 2023
Line 1:		Line 1:

-	====	+	==Human MBD4 glycosylase domain bound to DNA containing oxacarbenium-ion analog 1-aza-2'-deoxyribose==
-	<StructureSection load='7kzg' size='340' side='right'caption='[[7kzg]]' scene=''>	+	<StructureSection load='7kzg' size='340' side='right'caption='[[7kzg]], [[Resolution\|resolution]] 1.68Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id= OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol= FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[7kzg]] is a 3 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=7KZG OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7KZG FirstGlance]. <br>
-	</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=7kzg FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7kzg OCA], [https://pdbe.org/7kzg PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7kzg RCSB], [https://www.ebi.ac.uk/pdbsum/7kzg PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7kzg ProSAT]</span></td></tr>	+	</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models\|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution\|Resolution]] 1.68Å</td></tr>
		+	<tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=NA:SODIUM+ION'>NA</scene>, <scene name='pdbligand=NR1:(3R,4R)-3-HYDROXY-4-[(PHOSPHONOOXY)METHYL]PYRROLIDINIUM'>NR1</scene>, <scene name='pdbligand=PEG:DI(HYDROXYETHYL)ETHER'>PEG</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=7kzg FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7kzg OCA], [https://pdbe.org/7kzg PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7kzg RCSB], [https://www.ebi.ac.uk/pdbsum/7kzg PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7kzg ProSAT]</span></td></tr>
	</table>		</table>
		+	== Function ==
		+	[https://www.uniprot.org/uniprot/MBD4_HUMAN MBD4_HUMAN] Mismatch-specific DNA N-glycosylase involved in DNA repair. Has thymine glycosylase activity and is specific for G:T mismatches within methylated and unmethylated CpG sites. Can also remove uracil or 5-fluorouracil in G:U mismatches. Has no lyase activity. Was first identified as methyl-CpG-binding protein.<ref>PMID:10097147</ref> <ref>PMID:10930409</ref>
		+	<div style="background-color:#fffaf0;">
		+	== Publication Abstract from PubMed ==
		+	DNA glycosylases remove damaged or modified nucleobases by cleaving the N-glycosyl bond and the correct nucleotide is restored through subsequent base excision repair. In addition to excising threatening lesions, DNA glycosylases contribute to epigenetic regulation by mediating DNA demethylation and perform other important functions. However, the catalytic mechanism remains poorly defined for many glycosylases, including MBD4 (methyl-CpG binding domain IV), a member of the helix-hairpin-helix (HhH) superfamily. MBD4 excises thymine from G.T mispairs, suppressing mutations caused by deamination of 5-methylcytosine, and it removes uracil and modified uracils (e.g., 5-hydroxymethyluracil) mispaired with guanine. To investigate the mechanism of MBD4 we solved high-resolution structures of enzyme-DNA complexes at three stages of catalysis. Using a non-cleavable substrate analog, 2'-deoxy-pseudouridine, we determined the first structure of an enzyme-substrate complex for wild-type MBD4, which confirms interactions that mediate lesion recognition and suggests that a catalytic Asp, highly conserved in HhH enzymes, binds the putative nucleophilic water molecule and stabilizes the transition state. Observation that mutating the Asp (to Gly) reduces activity by 2700-fold indicates an important role in catalysis, but probably not one as the nucleophile in a double-displacement reaction, as previously suggested. Consistent with direct-displacement hydrolysis, a structure of the enzyme-product complex indicates a reaction leading to inversion of configuration. A structure with DNA containing 1-azadeoxyribose models a potential oxacarbenium-ion intermediate and suggests the Asp could facilitate migration of the electrophile towards the nucleophilic water. Finally, the structures provide detailed snapshots of the HhH motif, informing how these ubiquitous metal-binding elements mediate DNA binding.
		+
		+	Structural Insights into the Mechanism of Base Excision by MBD4.,Pidugu LS, Bright H, Lin WJ, Majumdar C, Van Ostrand RP, David SS, Pozharski E, Drohat AC J Mol Biol. 2021 Jul 23;433(15):167097. doi: 10.1016/j.jmb.2021.167097. Epub 2021 , Jun 6. PMID:34107280<ref>PMID:34107280</ref>
		+
		+	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
		+	</div>
		+	<div class="pdbe-citations 7kzg" style="background-color:#fffaf0;"></div>
		+
		+	==See Also==
		+	*[[Methyl CpG binding protein 3D structures\|Methyl CpG binding protein 3D structures]]
		+	== References ==
		+	<references/>
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
		+	[[Category: Homo sapiens]]
	[[Category: Large Structures]]		[[Category: Large Structures]]
-	[[Category: ~~Z-disk~~]]	+	[[Category: Drohat AC]]
		+	[[Category: Pidugu LS]]
		+	[[Category: Pozharski E]]

OCA at 06:15, 10 November 2021

2021-11-10T06:15:25Z

←Older revision		Revision as of 06:15, 10 November 2021
Line 1:		Line 1:
-	'''Unreleased structure'''

-	~~The entry~~ 7kzg ~~is ON HOLD until Paper Publication~~	+	====
-		+	<StructureSection load='7kzg' size='340' side='right'caption='[[7kzg]]' scene=''>
-	~~Authors~~: ~~Pidugu, L~~.S.~~, Pozharski, E~~.~~, Drohat, A~~.C.	+	== Structural highlights ==
-		+	<table><tr><td colspan='2'>Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id= OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol= FirstGlance]. <br>
-	~~Description~~: ~~Human MBD4 glycosylase domain bound to DNA containing oxacarbenium-ion analog 1-aza-2~~'~~-deoxyribose~~	+	</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=7kzg FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7kzg OCA], [https://pdbe.org/7kzg PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7kzg RCSB], [https://www.ebi.ac.uk/pdbsum/7kzg PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7kzg ProSAT]</span></td></tr>
-	[[~~Category~~: ~~Unreleased Structures~~]]	+	</table>
-	[[~~Category~~: ~~Pozharski~~, E]]	+	__TOC__
-	[[Category: ~~Drohat, A.C~~]]	+	</StructureSection>
-	[[Category: ~~Pidugu, L.S~~]]	+	[[Category: Large Structures]]
		+	[[Category: Z-disk]]

OCA at 05:49, 6 January 2021

2021-01-06T05:49:36Z

←Older revision		Revision as of 05:49, 6 January 2021
Line 1:		Line 1:
	'''Unreleased structure'''		'''Unreleased structure'''

-	The entry 7kzg is ON HOLD	+	The entry 7kzg is ON HOLD until Paper Publication

	Authors: Pidugu, L.S., Pozharski, E., Drohat, A.C.		Authors: Pidugu, L.S., Pozharski, E., Drohat, A.C.
Line 7:		Line 7:
	Description: Human MBD4 glycosylase domain bound to DNA containing oxacarbenium-ion analog 1-aza-2'-deoxyribose		Description: Human MBD4 glycosylase domain bound to DNA containing oxacarbenium-ion analog 1-aza-2'-deoxyribose
	[[Category: Unreleased Structures]]		[[Category: Unreleased Structures]]
-	[[Category: Drohat, A.C]]
	[[Category: Pozharski, E]]		[[Category: Pozharski, E]]
		+	[[Category: Drohat, A.C]]
	[[Category: Pidugu, L.S]]		[[Category: Pidugu, L.S]]

OCA: Protected "7kzg" [edit=sysop:move=sysop]

2020-12-16T11:17:46Z

Protected "7kzg" [edit=sysop:move=sysop]

←Older revision

Revision as of 11:17, 16 December 2020

OCA: New page: '''Unreleased structure''' The entry 7kzg is ON HOLD Authors: Pidugu, L.S., Pozharski, E., Drohat, A.C. Description: Human MBD4 glycosylase domain bound to DNA containing oxacarbenium-...

2020-12-16T11:17:45Z

New page: '''Unreleased structure''' The entry 7kzg is ON HOLD Authors: Pidugu, L.S., Pozharski, E., Drohat, A.C. Description: Human MBD4 glycosylase domain bound to DNA containing oxacarbenium-...

New page

'''Unreleased structure'''

The entry 7kzg is ON HOLD

Authors: Pidugu, L.S., Pozharski, E., Drohat, A.C.

Description: Human MBD4 glycosylase domain bound to DNA containing oxacarbenium-ion analog 1-aza-2'-deoxyribose
[[Category: Unreleased Structures]]
[[Category: Drohat, A.C]]
[[Category: Pozharski, E]]
[[Category: Pidugu, L.S]]