1skm | pdb_00001skm

HhaI methyltransferase in complex with DNA containing an abasic south carbocyclic sugar at its target site

spinqualitylabelsall models 1skm, resolution 2.20Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 1skm is a 3 chain structure with sequence from "bacillus_x"_pritchett_and_stillman_1919 "bacillus x" pritchett and stillman 1919. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Ligands: SAH NonStd Res: HCX Related: 1hmy, 1mht, 1fjx, 9mht Gene: HHAIM ("Bacillus X" Pritchett and Stillman 1919) Activity: DNA (cytosine-5-)-methyltransferase, with EC number 2.1.1.37 Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function [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 Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf. Publication Abstract from PubMed Rotation of a DNA or RNA nucleotide out of the double helix and into a protein pocket ('base flipping') is a mechanistic feature common to some DNA/RNA-binding proteins. Here, we report the structure of HhaI methyltransferase in complex with DNA containing a south-constrained abasic carbocyclic sugar at the target site in the presence of the methyl donor byproduct AdoHcy. Unexpectedly, the locked south pseudosugar appears to be trapped in the middle of the flipping pathway via the DNA major groove, held in place primarily through Van der Waals contacts with a set of invariant amino acids. Molecular dynamics simulations indicate that the structural stabilization observed with the south-constrained pseudosugar will not occur with a north-constrained pseudosugar, which explains its lowered binding affinity. Moreover, comparison of structural transitions of the sugar and phosphodiester backbone observed during computational studies of base flipping in the M.HhaI-DNA-AdoHcy ternary complex indicate that the south-constrained pseudosugar induces a conformation on the phosphodiester backbone that corresponds to that of a discrete intermediate of the base-flipping pathway. As previous crystal structures of M.HhaI ternary complex with DNA displayed the flipped sugar moiety in the antipodal north conformation, we suggest that conversion of the sugar pucker from south to north beyond the middle of the pathway is an essential part of the mechanism through which flipping must proceed to reach its final destination. We also discuss the possibility of the south-constrained pseudosugar mimicking a transition state in the phosphodiester and sugar moieties that occurs during DNA base flipping in the presence of M.HhaI. Caught in the act: visualization of an intermediate in the DNA base-flipping pathway induced by HhaI methyltransferase.,Horton JR, Ratner G, Banavali NK, Huang N, Choi Y, Maier MA, Marquez VE, MacKerell AD Jr, Cheng X Nucleic Acids Res. 2004 Jul 23;32(13):3877-86. Print 2004. PMID:15273274 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also DNA methyltransferase 3D structures

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