2hos
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(New page: 200px<br /><applet load="2hos" size="450" color="white" frame="true" align="right" spinBox="true" caption="2hos, resolution 1.90Å" /> '''Phage-Selected Homeo...)
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Revision as of 09:45, 21 November 2007
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Phage-Selected Homeodomain Bound to Unmodified DNA
Overview
The homeodomain (HD)-DNA interface has been conserved over 500 million, years of evolution. Despite this conservation, we have successfully, re-engineered the engrailed HD to specifically recognize an unnatural, nucleotide using a phage display selection. Here we report the synthesis, of novel nucleosides and the selection of mutant HDs that bind these, nucleotides using phage display. The high-resolution crystal structure of, one mutant in complex with modified and unmodified DNA demonstrates that, even with the substantial perturbation to the interface, this selected, mutant retains a canonical HD structure. Dissection of the contributions, due to each of the selected mutations reveals that the majority of the, modification-specific binding is accomplished by a single mutation (I47G), but that the remaining mutations retune the stability of the HD. These, results afford a detailed look at a re-engineered protein-DNA interaction, and provide insight into the opportunities for re-engineering highly, conserved interfaces.
About this Structure
2HOS is a Single protein structure of sequence from Drosophila melanogaster with 3MO and GOL as ligands. Full crystallographic information is available from OCA.
Reference
Structure and properties of a re-engineered homeodomain protein-DNA interface., Simon MD, Feldman ME, Rauh D, Maris AE, Wemmer DE, Shokat KM, ACS Chem Biol. 2006 Dec 15;1(12):755-60. PMID:17240973
Page seeded by OCA on Wed Nov 21 11:52:43 2007
