TY - JOUR
T1 - Structure of a binary complex of HhaI methyltransferase with S-adenosyl-L-methionine formed in the presence of a short non-specific DNA oligonucleotide
AU - O'Gara, Margaret
AU - Zhang, Xing
AU - Roberts, Richard J.
AU - Cheng, Xiaodong
N1 - Funding Information:
We thank J. R. Horton, M. Capel, and L. Berman for help with X-ray data collection. M.O’G. was supported in part by a National Institutes of Health fellowship (GM17052). Work was supported in part by National Institutes of Health Grants GM46127 to R.J.R. and GM49245 to X.C.
PY - 1999/3/26
Y1 - 1999/3/26
N2 - We have determined a structure for a complex formed between HhaI methyltransferase (M. HhaI) and S-adenosyl-L-methionine (AdoMet) in the presence of a non-specific short oligonucleotide. M. HhaI binds to the non-specific short oligonucleotides in solution. Although no DNA is incorporated in the crystal, AdoMet binds in a primed orientation, identical with that observed in the ternary complex of the enzyme, cognate DNA, and AdoMet or S-adenosyl-L-homocysteine (AdoHcy). This orientation differs from the previously observed unprimed orientation in the M.HhaI-AdoMet binary complex, where the S+-CH3 unit of AdoMet is protected by a favorable cation-π interaction with Trp41. The structure suggests that the presence of DNA can guide AdoMet into the primed orientation. These results shed new light on the proposed ordered mechanism of binding and explains the stable association between AdoMet and M. HhaI.
AB - We have determined a structure for a complex formed between HhaI methyltransferase (M. HhaI) and S-adenosyl-L-methionine (AdoMet) in the presence of a non-specific short oligonucleotide. M. HhaI binds to the non-specific short oligonucleotides in solution. Although no DNA is incorporated in the crystal, AdoMet binds in a primed orientation, identical with that observed in the ternary complex of the enzyme, cognate DNA, and AdoMet or S-adenosyl-L-homocysteine (AdoHcy). This orientation differs from the previously observed unprimed orientation in the M.HhaI-AdoMet binary complex, where the S+-CH3 unit of AdoMet is protected by a favorable cation-π interaction with Trp41. The structure suggests that the presence of DNA can guide AdoMet into the primed orientation. These results shed new light on the proposed ordered mechanism of binding and explains the stable association between AdoMet and M. HhaI.
KW - Cation-π interactions
KW - DNA methyltransferase
KW - Primed AdoMet binding orientation
KW - Protein-DNA non-specific binding
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U2 - 10.1006/jmbi.1999.2608
DO - 10.1006/jmbi.1999.2608
M3 - Article
C2 - 10080885
AN - SCOPUS:0033605827
SN - 0022-2836
VL - 287
SP - 201
EP - 209
JO - Journal of Molecular Biology
JF - Journal of Molecular Biology
IS - 2
ER -