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MutH Complexed with Hemi- and Unmethylated DNAs: Coupling Base Recognition and DNA Cleavage

Lee, Jae Young and Chang, Judy and Joseph, Nimesh and Ghirlando, Rodolfo and Rao, Desirazu N and Yang, Wei (2005) MutH Complexed with Hemi- and Unmethylated DNAs: Coupling Base Recognition and DNA Cleavage. In: Molecular Cell, 20 (1). pp. 155-166.

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MutH initiates mismatch repair by nicking the transiently unmethylated daughter strand 5' to a GATC sequence. Here, we report crystal structures of MutH complexed with hemimethylated and unmethylated GATC substrates. Both structures contain two $Ca^{2+}$ ions jointly coordinated by a conserved aspartate and the scissile phosphate, as observed in the restriction endonucleases BamHI and BgII. In the hemimethylated complexes, the active site is more compact and DNA cleavage is more efficient. The Lys residue in the conserved DEK motif coordinates the nucleophilic water in conjunction with the phosphate 3' to the scissile bond; the same Lys is also hydrogen bonded with a carbonyl oxygen in the DNA binding module. We propose that this Lys, which is conserved in many restriction endonucleases and is replaced by Glu or Gin in BamHI and BgIII, is a sensor for DNA binding and the linchpin that couples base recognition and DNA cleavage.

Item Type: Journal Article
Publication: Molecular Cell
Publisher: Elsevier Science
Additional Information: Copyright for this article belongs to Elsevier.
Department/Centre: Division of Biological Sciences > Biochemistry
Date Deposited: 29 Nov 2005
Last Modified: 27 Aug 2008 11:34
URI: http://eprints.iisc.ac.in/id/eprint/4219

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