Direct transfer of extended groups from synthetic cofactors by DNA methyltransferases

被引:185
作者
Dalhoff, C
Lukinavicius, G
Klimasauskas, S
Weinhold, E
机构
[1] Inst Biotechnol, Lab Biol DNA Modificat, LT-02241 Vilnius, Lithuania
[2] Rhein Westfal TH Aachen, Inst Organ Chem, D-52056 Aachen, Germany
关键词
D O I
10.1038/nchembio754
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Adenosyl-L-methionine (AdoMet) is the major methyl donor for biological methylation reactions catalyzed by methyltransferases. We report the first chemical synthesis of AdoMet analogs with extended carbon chains replacing the methyl group and their evaluation as cofactors for all three classes of DNA methyltransferases. Extended groups containing a double or triple bond in the beta position to the sulfonium center were transferred onto DNA in a catalytic and sequence-specific manner, demonstrating a high utility of such synthetic cofactors for targeted functionalization of biopolymers.
引用
收藏
页码:31 / 32
页数:2
相关论文
共 15 条
[1]   POTENTIAL INHIBITORS OF S-ADENOSYLMETHIONINE-DEPENDENT METHYLTRANSFERASES .5. ROLE OF ASYMMETRIC SULFONIUM POLE IN ENZYMATIC BINDING OF S-ADENOSYL-L-METHIONINE [J].
BORCHARDT, RT ;
WU, YS .
JOURNAL OF MEDICINAL CHEMISTRY, 1976, 19 (09) :1099-1103
[3]  
CHENG X, 1999, S ADENOSYLMETHIONINE, P392
[4]   S-ADENOSYLMETHIONINE - THE RELATION OF CONFIGURATION AT THE SULFONIUM CENTER TO ENZYMATIC REACTIVITY [J].
DELAHABA, G ;
JAMIESON, GA ;
MUDD, SH ;
RICHARDS, HH .
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY, 1959, 81 (15) :3975-3980
[5]   Structure of the N6-adenine DNA methyltransferase M•Taql in complex with DNA and a cofactor analog [J].
Goedecke, K ;
Pignot, M ;
Goody, RS ;
Scheidig, AJ ;
Weinhold, E .
NATURE STRUCTURAL BIOLOGY, 2001, 8 (02) :121-125
[6]   Eukaryotic cytosine methyltransferases [J].
Goll, MG ;
Bestor, TH .
ANNUAL REVIEW OF BIOCHEMISTRY, 2005, 74 :481-514
[7]   STEREOCHEMICAL STUDIES OF THE C-METHYLATION OF DEOXYCYTIDINE CATALYZED BY HHAL METHYLASE AND THE N-METHYLATION OF DEOXYADENOSINE CATALYZED BY ECORI METHYLASE [J].
HO, DK ;
WU, JC ;
SANTI, DV ;
FLOSS, HG .
ARCHIVES OF BIOCHEMISTRY AND BIOPHYSICS, 1991, 284 (02) :264-269
[8]   HHAL METHYLTRANSFERASE FLIPS ITS TARGET BASE OUT OF THE DNA HELIX [J].
KLIMASAUSKAS, S ;
KUMAR, S ;
ROBERTS, RJ ;
CHENG, XD .
CELL, 1994, 76 (02) :357-369
[9]  
Merkiene E, 1998, BIOL CHEM, V379, P569
[10]   THE DNA-BINDING AFFINITY OF HHAI METHYLASE IS INCREASED BY A SINGLE AMINO-ACID SUBSTITUTION IN THE CATALYTIC CENTER [J].
MI, S ;
ROBERTS, RJ .
NUCLEIC ACIDS RESEARCH, 1993, 21 (10) :2459-2464