View source for 6lzk


==Aquifex aeolicus MutL ATPase domain with K252N mutation==
<StructureSection load='6lzk' size='340' side='right'caption='[[6lzk]], [[Resolution|resolution]] 3.16&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[6lzk]] is a 3 chain structure with sequence from [https://en.wikipedia.org/wiki/Aquifex_aeolicus_VF5 Aquifex aeolicus VF5]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6LZK OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6LZK 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]] 3.1594963&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=NA:SODIUM+ION'>NA</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=6lzk FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6lzk OCA], [https://pdbe.org/6lzk PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6lzk RCSB], [https://www.ebi.ac.uk/pdbsum/6lzk PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6lzk ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/MUTL_AQUAE MUTL_AQUAE] This protein is involved in the repair of mismatches in DNA. It is required for dam-dependent methyl-directed DNA mismatch repair. May act as a "molecular matchmaker", a protein that promotes the formation of a stable complex between two or more DNA-binding proteins in an ATP-dependent manner without itself being part of a final effector complex (By similarity).
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
In humans, mutations in genes encoding homologs of the DNA mismatch repair endonuclease MutL cause a hereditary cancer that is known as Lynch syndrome. Here, we determined the crystal structures of the N-terminal domain (NTD) of MutL from the thermophilic eubacterium Aquifex aeolicus (aqMutL) complexed with ATP analogs at 1.69-1.73 A. The structures revealed significant structural similarities to those of a human MutL homolog, Postmeiotic segregation increased 2 (PMS2). We introduced five Lynch syndrome-associated mutations clinically found in human PMS2 into the aqMutL NTD and investigated the protein stability, ATPase activity, and DNA-binding ability of these protein variants. Among the mutations studied, the most unexpected results were obtained for the residue Ser34. Ser34 (Ser46 in PMS2) is located at a previously-identified Bergerat ATP-binding fold. We found that the S34I aqMutL NTD retains ATPase and DNA-binding activities. Interestingly, CD spectrometry and trypsin limited proteolysis indicated disruption of a secondary structure element of the S34I NTD, destabilizing the overall structure of the aqMutL NTD. In agreement with this, the recombinant human PMS2 S46I NTD was easily digested in the host Escherichia coli cells. Moreover, other mutations resulted in reduced DNA-binding or ATPase activity. In summary, using the thermostable aqMutL protein as a model molecule, we have experimentally determined the effects of the mutations on MutL endonuclease; we discuss the pathological effects of the corresponding mutations in human PMS2.

A Lynch syndrome-associated mutation at a Bergerat ATP-binding fold destabilizes the structure of the DNA mismatch repair endonuclease MutL.,Izuhara K, Fukui K, Murakawa T, Baba S, Kumasaka T, Uchiyama K, Yano T J Biol Chem. 2020 Jun 22. pii: RA120.013576. doi: 10.1074/jbc.RA120.013576. PMID:32571878<ref>PMID:32571878</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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<div class="pdbe-citations 6lzk" style="background-color:#fffaf0;"></div>

==See Also==
*[[DNA mismatch repair protein 3D structures|DNA mismatch repair protein 3D structures]]
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Aquifex aeolicus VF5]]
[[Category: Large Structures]]
[[Category: Fukui K]]
[[Category: Izuhara K]]
[[Category: Yano T]]