Solution Structure of the
Methyl-CpG Binding Domain of Human MBD1 in Complex with Methylated DNA
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DNA methylation is an important factor in control of gene
expression in organisms. Increased DNA methylation is associated with
gene silencing. Improper methylation can induce many damaging
genetic defects in organisms. Increased methylation of tumor
suppressor genes (which inhibits their transcription) or decreased
methylation of genes that promote cell growth (possible protooncogenes)
have been carcinogenesis. Methylation of DNA is catalyzed by DNA
methyltransferases. The structure here is the methyl-CpG binding domains (MBDs)
of human methylated DNA Binding Protein 1 (MDB1) bound to methylated DNA. .
For more information see
Biochemistry Online: Chapter 5D - Binding and the Control of Gene
II. General Structure
Methylated DNA and MDB1 protein (methyl group in yellow)
MDB1 protein Backbone
Major/Minor Grooves with methyl groups
Backbone and sidechains of MDB1 protein
Cartoon, Hbonds and
Active site residues (Val 20, Arg 22, Tyr 34, Arg 44, Ser 45)
MDB1 is able to bind to methylated DNA through the use of 5 highly conserved
Methylated DNA (methyl groups in yellow) and MDB1 active site residues
(Val 20, Arg 22, Tyr 34, Arg 44, Ser 45)
Loop L1 (residues 22-30)
This loop undergoes a conformational change to allow it to bind to the major
groove of DNA.
Methylated DNA and binding site of MDB1 (Loop L1)
Methylated DNA with binding MDB1 and active site.
The L1 loop binds to DNA and the active site is then able to interact with the
methyl groups present.