5zyw

From Proteopedia

(Difference between revisions)

Current revision

The crystal structure of apo-HsMGME1 with Mn2+

Structural highlights

5zyw is a 1 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 2.2Å
Ligands:	, ,
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Disease

MGME1_HUMAN Progressive external ophthalmoplegia - myopathy - emaciation. The disease may be caused by mutations affecting the gene represented in this entry.

Function

MGME1_HUMAN Metal-dependent single-stranded DNA (ssDNA) exonuclease involved in mitochondrial genome maintenance. Has preference for 5'-3' exonuclease activity but is also capable of endoduclease activity on linear substrates. Necessary for maintenance of proper 7S DNA levels. Probably involved in mitochondrial DNA (mtDNA) repair, possibly via the processing of displaced DNA containing Okazaki fragments during RNA-primed DNA synthesis on the lagging strand or via processing of DNA flaps during long-patch base excision repair. Specifically binds 5-hydroxymethylcytosine (5hmC)-containing DNA in stem cells.[HAMAP-Rule:MF_03030]^[1] ^[2]

Publication Abstract from PubMed

Mitochondrial nucleases play important roles in accurate maintenance and correct metabolism of mtDNA, the own genetic materials of mitochondria that are passed exclusively from mother to child. MGME1 is a highly conserved DNase that was discovered recently. Mutations in MGME1-coding gene lead to severe mitochondrial syndromes characterized by external ophthalmoplegia, emaciation, and respiratory failure in humans. Unlike many other nucleases that are distributed in multiple cellular organelles, human MGME1 is a mitochondria-specific nuclease; therefore, it can serve as an ideal target for treating related syndromes. Here, we report one HsMGME1-Mn2+ complex and three different HsMGME1-DNA complex structures. In combination with in vitro cleavage assays, our structures reveal the detailed molecular basis for substrate DNA binding and/or unwinding by HsMGME1. Besides the conserved two-cation-assisted catalytic mechanism, structural analysis of HsMGME1 and comparison with homologous proteins also clarified substrate binding and cleavage directionalities of the DNA double-strand break repair complexes RecBCD and AddAB.

Structural insights into DNA degradation by human mitochondrial nuclease MGME1.,Yang C, Wu R, Liu H, Chen Y, Gao Y, Chen X, Li Y, Ma J, Li J, Gan J Nucleic Acids Res. 2018 Sep 21. pii: 5104735. doi: 10.1093/nar/gky855. PMID:30247721^[3]

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

References

↑ Kornblum C, Nicholls TJ, Haack TB, Scholer S, Peeva V, Danhauser K, Hallmann K, Zsurka G, Rorbach J, Iuso A, Wieland T, Sciacco M, Ronchi D, Comi GP, Moggio M, Quinzii CM, DiMauro S, Calvo SE, Mootha VK, Klopstock T, Strom TM, Meitinger T, Minczuk M, Kunz WS, Prokisch H. Loss-of-function mutations in MGME1 impair mtDNA replication and cause multisystemic mitochondrial disease. Nat Genet. 2013 Feb;45(2):214-9. doi: 10.1038/ng.2501. Epub 2013 Jan 13. PMID:23313956 doi:http://dx.doi.org/10.1038/ng.2501
↑ Szczesny RJ, Hejnowicz MS, Steczkiewicz K, Muszewska A, Borowski LS, Ginalski K, Dziembowski A. Identification of a novel human mitochondrial endo-/exonuclease Ddk1/c20orf72 necessary for maintenance of proper 7S DNA levels. Nucleic Acids Res. 2013 Mar 1;41(5):3144-61. doi: 10.1093/nar/gkt029. Epub 2013, Jan 28. PMID:23358826 doi:http://dx.doi.org/10.1093/nar/gkt029
↑ Yang C, Wu R, Liu H, Chen Y, Gao Y, Chen X, Li Y, Ma J, Li J, Gan J. Structural insights into DNA degradation by human mitochondrial nuclease MGME1. Nucleic Acids Res. 2018 Sep 21. pii: 5104735. doi: 10.1093/nar/gky855. PMID:30247721 doi:http://dx.doi.org/10.1093/nar/gky855

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

Proteopedia Page Contributors and Editors (what is this?)

OCA

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

Categories: Homo sapiens | Large Structures | Gan J | Yang C

@@ Line 1: / Line 1: @@
-==crytal struture of apo-HsMGME1 with Mn2+==
+==The crystal structure of apo-HsMGME1 with Mn2+==
-<StructureSection load='5zyw' size='340' side='right' caption='[[5zyw]], [[Resolution|resolution]] 2.20&Aring;' scene=''>
+<StructureSection load='5zyw' size='340' side='right'caption='[[5zyw]], [[Resolution|resolution]] 2.20&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[5zyw]] is a 1 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=5ZYW OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5ZYW FirstGlance]. <br>
+<table><tr><td colspan='2'>[[5zyw]] is a 1 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=5ZYW OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5ZYW FirstGlance]. <br>
-</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=MN:MANGANESE+(II)+ION'>MN</scene>, <scene name='pdbligand=TLA:L(+)-TARTARIC+ACID'>TLA</scene></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]] 2.2&#8491;</td></tr>
-<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">MGME1, C20orf72, DDK1 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr>
+<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=MN:MANGANESE+(II)+ION'>MN</scene>, <scene name='pdbligand=TLA:L(+)-TARTARIC+ACID'>TLA</scene></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=5zyw FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5zyw OCA], [http://pdbe.org/5zyw PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5zyw RCSB], [http://www.ebi.ac.uk/pdbsum/5zyw PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5zyw ProSAT]</span></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=5zyw FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5zyw OCA], [https://pdbe.org/5zyw PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5zyw RCSB], [https://www.ebi.ac.uk/pdbsum/5zyw PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5zyw ProSAT]</span></td></tr>
 </table>
 == Disease ==
-[[http://www.uniprot.org/uniprot/MGME1_HUMAN MGME1_HUMAN]] Progressive external ophthalmoplegia - myopathy - emaciation. The disease may be caused by mutations affecting the gene represented in this entry.
+[https://www.uniprot.org/uniprot/MGME1_HUMAN MGME1_HUMAN] Progressive external ophthalmoplegia - myopathy - emaciation. The disease may be caused by mutations affecting the gene represented in this entry.
 == Function ==
-[[http://www.uniprot.org/uniprot/MGME1_HUMAN MGME1_HUMAN]] Metal-dependent single-stranded DNA (ssDNA) exonuclease involved in mitochondrial genome maintenance. Has preference for 5'-3' exonuclease activity but is also capable of endoduclease activity on linear substrates. Necessary for maintenance of proper 7S DNA levels. Probably involved in mitochondrial DNA (mtDNA) repair, possibly via the processing of displaced DNA containing Okazaki fragments during RNA-primed DNA synthesis on the lagging strand or via processing of DNA flaps during long-patch base excision repair. Specifically binds 5-hydroxymethylcytosine (5hmC)-containing DNA in stem cells.[HAMAP-Rule:MF_03030]<ref>PMID:23313956</ref> <ref>PMID:23358826</ref>
+[https://www.uniprot.org/uniprot/MGME1_HUMAN MGME1_HUMAN] Metal-dependent single-stranded DNA (ssDNA) exonuclease involved in mitochondrial genome maintenance. Has preference for 5'-3' exonuclease activity but is also capable of endoduclease activity on linear substrates. Necessary for maintenance of proper 7S DNA levels. Probably involved in mitochondrial DNA (mtDNA) repair, possibly via the processing of displaced DNA containing Okazaki fragments during RNA-primed DNA synthesis on the lagging strand or via processing of DNA flaps during long-patch base excision repair. Specifically binds 5-hydroxymethylcytosine (5hmC)-containing DNA in stem cells.[HAMAP-Rule:MF_03030]<ref>PMID:23313956</ref> <ref>PMID:23358826</ref>
 <div style="background-color:#fffaf0;">
 == Publication Abstract from PubMed ==
@@ Line 21: / Line 21: @@
 </div>
 <div class="pdbe-citations 5zyw" style="background-color:#fffaf0;"></div>
+==See Also==
+*[[Exonuclease 3D structures|Exonuclease 3D structures]]
 == References ==
 <references/>
 __TOC__
 </StructureSection>
-[[Category: Human]]
+[[Category: Homo sapiens]]
-[[Category: Gan, J]]
+[[Category: Large Structures]]
-[[Category: Yang, C]]
+[[Category: Gan J]]
-[[Category: Dna binding protein]]
+[[Category: Yang C]]
-[[Category: Dna complex]]
-[[Category: Dna exonuclease]]
-[[Category: Huamnmgme1]]
-[[Category: Hydrolase]]

5zyw

From Proteopedia

Current revision

The crystal structure of apo-HsMGME1 with Mn2+

Structural highlights

Disease

Function

Publication Abstract from PubMed

See Also

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

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