5lod

From Proteopedia

Crystal structure of HhaI DNA methyltransferase in APO form

Structural highlights

5lod is a 2 chain structure with sequence from Haemophilus parahaemolyticus. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:	X-ray diffraction, Resolution 1.9Å
Ligands:
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.

Publication Abstract from PubMed

AIM: DNA methyltransferases (DNMTs) are important drug targets for epigenetic therapy of cancer. Nowadays, non-nucleoside DNMT inhibitors are in development to address high toxicity of nucleoside analogs. However, these compounds still have low activity in cancer cells and mode of action of these compounds remains unclear. MATERIALS & METHODS: In this work, we studied maleimide derivatives of RG108 by biochemical, structural and computational approaches to highlight their inhibition mechanism on DNMTs. RESULTS: Findings demonstrated a correlation between cytotoxicity on mesothelioma cells of these compounds and their inhibitory potency against DNMTs. Noncovalent and covalent docking studies, supported by crystallographic (apo structure of M.HhaI) and differential scanning fluorimetry assays, provided detailed insights into their mode of action and revealed essential residues for the stabilization of such compounds inside DNMTs. [Formula: see text].

Inhibition studies of DNA methyltransferases by maleimide derivatives of RG108 as non-nucleoside inhibitors.,Rondelet G, Fleury L, Faux C, Masson V, Dubois J, Arimondo PB, Willems L, Wouters J Future Med Chem. 2017 Aug 10. doi: 10.4155/fmc-2017-0074. PMID:28795598^[1]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

References

↑ Rondelet G, Fleury L, Faux C, Masson V, Dubois J, Arimondo PB, Willems L, Wouters J. Inhibition studies of DNA methyltransferases by maleimide derivatives of RG108 as non-nucleoside inhibitors. Future Med Chem. 2017 Aug 10. doi: 10.4155/fmc-2017-0074. PMID:28795598 doi:http://dx.doi.org/10.4155/fmc-2017-0074