TY - JOUR
T1 - The cell cycle-regulated DNA adenine methyltransferase CcrM opens a bubble at its DNA recognition site
AU - Horton, John R.
AU - Woodcock, Clayton B.
AU - Opot, Sifa B.
AU - Reich, Norbert O.
AU - Zhang, Xing
AU - Cheng, Xiaodong
N1 - Funding Information:
We thank Dr. S.J. Benkovic of Pennsylvania State University for initial plasmid containing C. crescentus CcrM, Dr. Robert M. Blumenthal of the University of Toledo College of Medicine for comments on paper, and Mr. Sarath Chand Pathuri for discussion on CcrM. S.B.O. was supported by the MD Anderson Cancer Center Partnership for Careers in Cancer Science and Medicine Summer Program. This work was supported by grants from NIH (GM049245) and CPRIT (RR160029).
Publisher Copyright:
© 2019, The Author(s).
PY - 2019/12/1
Y1 - 2019/12/1
N2 - The Caulobacter crescentus cell cycle-regulated DNA methyltransferase (CcrM) methylates the adenine of hemimethylated GANTC after replication. Here we present the structure of CcrM in complex with double-stranded DNA containing the recognition sequence. CcrM contains an N-terminal methyltransferase domain and a C-terminal nonspecific DNA-binding domain. CcrM is a dimer, with each monomer contacting primarily one DNA strand: the methyltransferase domain of one molecule binds the target strand, recognizes the target sequence, and catalyzes methyl transfer, while the C-terminal domain of the second molecule binds the non-target strand. The DNA contacts at the 5-base pair recognition site results in dramatic DNA distortions including bending, unwinding and base flipping. The two DNA strands are pulled apart, creating a bubble comprising four recognized base pairs. The five bases of the target strand are recognized meticulously by stacking contacts, van der Waals interactions and specific Watson–Crick polar hydrogen bonds to ensure high enzymatic specificity.
AB - The Caulobacter crescentus cell cycle-regulated DNA methyltransferase (CcrM) methylates the adenine of hemimethylated GANTC after replication. Here we present the structure of CcrM in complex with double-stranded DNA containing the recognition sequence. CcrM contains an N-terminal methyltransferase domain and a C-terminal nonspecific DNA-binding domain. CcrM is a dimer, with each monomer contacting primarily one DNA strand: the methyltransferase domain of one molecule binds the target strand, recognizes the target sequence, and catalyzes methyl transfer, while the C-terminal domain of the second molecule binds the non-target strand. The DNA contacts at the 5-base pair recognition site results in dramatic DNA distortions including bending, unwinding and base flipping. The two DNA strands are pulled apart, creating a bubble comprising four recognized base pairs. The five bases of the target strand are recognized meticulously by stacking contacts, van der Waals interactions and specific Watson–Crick polar hydrogen bonds to ensure high enzymatic specificity.
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U2 - 10.1038/s41467-019-12498-7
DO - 10.1038/s41467-019-12498-7
M3 - Article
C2 - 31601797
AN - SCOPUS:85073112373
SN - 2041-1723
VL - 10
JO - Nature communications
JF - Nature communications
IS - 1
M1 - 4600
ER -