Switching DNA-binding specificity by unnatural amino acid substitution
IR@IICB: CSIR-Indian Institute of Chemical Biology, Kolkata
View Archive Info| Field | Value | |
| Title |
Switching DNA-binding specificity by unnatural
amino acid substitution
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| Creator |
Maiti, Atanu
Roy, Siddhartha |
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| Subject |
Structural Biology & Bioinformatics
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| Description |
The specificity of protein–nucleic acid recognition
is believed to originate largely from hydrogen bonding
between protein polar atoms, primarily side-chain
and polar atoms of nucleic acid bases. One way to
design new nucleic acid binding proteins of novel
specificity is by structure-guided alterations of the
hydrogen bonding patterns of a nucleic acid–protein
complex. We have used cI repressor of bacteriophage
l as a model system. In the l-repressor–DNA
complex, the «-NH2 group (hydrogen bond donor)
of lysine-4 of l-repressor forms hydrogen bonds
with the amide carbonyl atom of asparagine-55
(acceptor) and the O6 (acceptor) of CG6 of operator
site OL1. Substitution of lysine-4 (two donors) by isosteric
S-(2-hydroxyethyl)-cysteine (one donor and
one acceptor), by site-directed mutagenesis and chemical
modification, leads to switch of binding specificity
of l-repressor from C:G to T:A at position 6
of OL1. This suggests that unnatural amino acid
substitutions could be a simple way of generating
nucleic acid binding proteins of altered specificity
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| Publisher |
Oxford University Press
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| Date |
2005
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| Type |
Article
PeerReviewed |
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| Format |
application/pdf
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| Identifier |
http://www.eprints.iicb.res.in/578/1/NUCLEIC_ACIDS_RESEARCH__33(18)_5896%2D5903;2005[113].pdf
Maiti, Atanu and Roy, Siddhartha (2005) Switching DNA-binding specificity by unnatural amino acid substitution. Nucleic Acids Research, 33 (18). pp. 5896-5903. |
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| Relation |
http://dx.doi.org/10.1093/nar/gki899
http://www.eprints.iicb.res.in/578/ |
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