SNAP output for PDB entry 8fs1 [SNAP web server]

PDB-id

8fs1; SNAP-derived features in text and JSON formats; DNAproDB

Class

transferase-DNA-inhibitor

Method

X-ray (2.74 Å)

Summary

Cama adenine methyltransferase complexed to cognate substrate DNA and inhibitor 11a (yd905)

Reference

Zhou J, Deng Y, Iyamu ID, Horton JR, Yu D, Hajian T, Vedadi M, Rotili D, Mai A, Blumenthal RM, Zhang X, Huang R, Cheng X (2023): "Comparative Study of Adenosine Analogs as Inhibitors of Protein Arginine Methyltransferases and a Clostridioides difficile- Specific DNA Adenine Methyltransferase." Acs Chem.Biol., 18, 734-745. doi: 10.1021/acschembio.3c00035.

Abstract

S-Adenosyl-l-methionine (SAM) analogs are adaptable tools for studying and therapeutically inhibiting SAM-dependent methyltransferases (MTases). Some MTases play significant roles in host-pathogen interactions, one of which is Clostridioides difficile-specific DNA adenine MTase (CamA). CamA is needed for efficient sporulation and alters persistence in the colon. To discover potent and selective CamA inhibitors, we explored modifications of the solvent-exposed edge of the SAM adenosine moiety. Starting from the two parental compounds (