Clostridioides difficile specific DNA adenine methyltransferase CamA squeezes and flips adenine out of DNA helix.

Nature Communications
Jujun ZhouXiaodong Cheng

Abstract

Clostridioides difficile infections are an urgent medical problem. The newly discovered C. difficile adenine methyltransferase A (CamA) is specified by all C. difficile genomes sequenced to date (>300), but is rare among other bacteria. CamA is an orphan methyltransferase, unassociated with a restriction endonuclease. CamA-mediated methylation at CAAAAA is required for normal sporulation, biofilm formation, and intestinal colonization by C. difficile. We characterized CamA kinetic parameters, and determined its structure bound to DNA containing the recognition sequence. CamA contains an N-terminal domain for catalyzing methyl transfer, and a C-terminal DNA recognition domain. Major and minor groove DNA contacts in the recognition site involve base-specific hydrogen bonds, van der Waals contacts and the Watson-Crick pairing of a rearranged A:T base pair. These provide sufficient sequence discrimination to ensure high specificity. Finally, the surprisingly weak binding of the methyl donor S-adenosyl-L-methionine (SAM) might provide avenues for inhibiting CamA activity using SAM analogs.

References

Sep 20, 1989·Journal of Molecular Biology·T Tomcsanyi, D E Berg
Oct 9, 1987·Cell·D Morisato, N Kleckner
Feb 1, 1988·Journal of Bacteriology·S A McCommas, M Syvanen
Apr 1, 1988·Proceedings of the National Academy of Sciences of the United States of America·J C MakrisW S Reznikoff
Jan 1, 1995·Annual Review of Biophysics and Biomolecular Structure·X Cheng
Feb 1, 1995·Current Opinion in Structural Biology·X Cheng
Mar 17, 1995·Journal of Molecular Biology·G SchluckebierX Cheng
Nov 8, 1994·Proceedings of the National Academy of Sciences of the United States of America·J LabahnW Saenger
Jan 11, 1994·Nucleic Acids Research·S KumarG G Wilson
Feb 6, 1996·Proceedings of the National Academy of Sciences of the United States of America·C StephensL Shapiro
Apr 18, 1998·Proceedings of the National Academy of Sciences of the United States of America·A J BerdisS J Benkovic
Jun 25, 2002·Journal of Molecular Biology·Sabine UrigAlbert Jeltsch
Aug 31, 2002·Proceedings of the National Academy of Sciences of the United States of America·Aaron HerndayDavid Low
Feb 20, 2003·Journal of Bacteriology·Jennifer Wyrzykowski, Michael R Volkert
Jun 27, 2003·Trends in Biochemical Sciences·Heidi L SchubertXiaodong Cheng
Aug 26, 2003·Nature Structural Biology·Zhe YangXiaodong Cheng
Jul 27, 2004·Nucleic Acids Research·Edit TímárPál Venetianer
Dec 2, 2004·Acta Crystallographica. Section D, Biological Crystallography·Paul Emsley, Kevin Cowtan
May 26, 2005·Protein Expression and Purification·F William Studier
Mar 10, 2006·Journal of Molecular Biology·John R HortonXiaodong Cheng
Aug 19, 2008·Journal of Molecular Biology·Stacey N Peterson, Norbert O Reich
May 26, 2009·Acta Crystallographica. Section D, Biological Crystallography·Thomas C TerwilligerLi Wei Hung
Feb 4, 2010·Acta Crystallographica. Section D, Biological Crystallography·Paul D AdamsPeter H Zwart
Feb 23, 2011·Journal of Molecular Biology·Tetsuya KawamuraFrederick W Dahlquist
Oct 11, 2012·The Journal of Biological Chemistry·Scott Horowitz, Raymond C Trievel
Nov 8, 2014·Nucleic Acids Research·Richard J RobertsDana Macelis
Feb 26, 2015·The New England Journal of Medicine·Fernanda C LessaL Clifford McDonald
Jun 13, 2015·Nature Communications·Yogesh K GuptaAneel K Aggarwal
Jun 13, 2015·Nucleic Acids Research·Xin DengChuan He
Nov 6, 2015·ACS Chemical Biology·Jing Zhang, Yujun George Zheng

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Citations

Aug 18, 2021·MSystems·Pedro H Oliveira
Sep 16, 2021·Epigenetics : Official Journal of the DNA Methylation Society·Jujun ZhouXiaodong Cheng

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PyMol
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