View source for 2z6u


==Ternary structure of the Glu119Ala M.HhaI, C5-Cytosine DNA methyltransferase, with unmodified DNA and AdoHcy==
<StructureSection load='2z6u' size='340' side='right'caption='[[2z6u]], [[Resolution|resolution]] 2.72&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[2z6u]] is a 3 chain structure with sequence from [https://en.wikipedia.org/wiki/Haemophilus_parahaemolyticus Haemophilus parahaemolyticus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2Z6U OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2Z6U 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]] 2.72&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=SAH:S-ADENOSYL-L-HOMOCYSTEINE'>SAH</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=2z6u FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2z6u OCA], [https://pdbe.org/2z6u PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2z6u RCSB], [https://www.ebi.ac.uk/pdbsum/2z6u PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2z6u ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/MTH1_HAEPH MTH1_HAEPH] This methylase recognizes the double-stranded sequence GCGC, causes specific methylation on C-2 on both strands, and protects the DNA from cleavage by the HhaI endonuclease.
== Evolutionary Conservation ==
[[Image:Consurf_key_small.gif|200px|right]]
Check<jmol>
  <jmolCheckbox>
    <scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/z6/2z6u_consurf.spt"</scriptWhenChecked>
    <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked>
    <text>to colour the structure by Evolutionary Conservation</text>
  </jmolCheckbox>
</jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/main_output.php?pdb_ID=2z6u ConSurf].
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== Publication Abstract from PubMed ==
The role of Glu119 in S-adenosyl-L-methionine-dependent DNA methyltransferase M.HhaI-catalyzed DNA methylation was studied. Glu119 belongs to the highly conserved Glu/Asn/Val motif found in all DNA C5-cytosine methyltransferases, and its importance for M.HhaI function remains untested. We show that formation of the covalent intermediate between Cys81 and the target cytosine requires Glu119, since conversion to Ala, Asp or Gln lowers the rate of methyl transfer 10(2)-10(6) fold. Further, unlike the wild-type M.HhaI, these mutants are not trapped by the substrate in which the target cytosine is replaced with the mechanism-based inhibitor 5-fluorocytosine. The DNA binding affinity for the Glu119Asp mutant is decreased 10(3)-fold. Thus, the ability of the enzyme to stabilize the extrahelical cytosine is coupled directly to tight DNA binding. The structures of the ternary protein/DNA/AdoHcy complexes for both the Glu119Ala and Glu119Gln mutants (2.70 A and 2.75 A, respectively) show that the flipped base is positioned nearly identically with that observed in the wild-type M.HhaI complex. A single water molecule in the Glu119Ala structure between Ala119 and the extrahelical cytosine N3 is lacking in the Glu119Gln and wild-type M.HhaI structures, and most likely accounts for this mutant's partial activity. Glu119 has essential roles in activating the target cytosine for nucleophilic attack and contributes to tight DNA binding.

AdoMet-dependent methyl-transfer: Glu119 is essential for DNA C5-cytosine methyltransferase M.HhaI.,Shieh FK, Reich NO J Mol Biol. 2007 Nov 9;373(5):1157-68. Epub 2007 Aug 19. PMID:17897676<ref>PMID:17897676</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 2z6u" style="background-color:#fffaf0;"></div>

==See Also==
*[[DNA methyltransferase 3D structures|DNA methyltransferase 3D structures]]
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Haemophilus parahaemolyticus]]
[[Category: Large Structures]]
[[Category: Shieh FK]]