1t97
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(New page: 200px<br /><applet load="1t97" size="450" color="white" frame="true" align="right" spinBox="true" caption="1t97, resolution 2.70Å" /> '''Use of sequence dupl...)
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Revision as of 00:58, 21 November 2007
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Use of sequence duplication to engineer a ligand-triggered long-distance molecular switch in T4 lysosyme
Overview
We have designed a molecular switch in a T4 lysozyme construct that, controls a large-scale translation of a duplicated helix. As shown by, crystal structures of the construct with the switch on and off, the, conformational change is triggered by the binding of a ligand (guanidinium, ion) to a site that in the wild-type protein was occupied by the guanidino, head group of an Arg. In the design template, a duplicated helix is, flanked by two loop regions of different stabilities. In the "on" state, the N-terminal loop is weakly structured, whereas the C-terminal loop has, a well defined conformation that is stabilized by means of nonbonded, interactions with the Arg head group. The truncation of the Arg to Ala, destabilizes this loop and switches the protein to the "off" state, in, which the duplicated helix is translocated approximately 20 A. Guanidinium, binding restores the key interactions, restabilizes the C-terminal loop, and restores the "on" state. Thus, the presence of an external ligand, which is unrelated to the catalytic activity of the enzyme, triggers the, inserted helix to translate 20 A away from the binding site. The results, illustrate a proposed mechanism for protein evolution in which sequence, duplication followed by point mutation can lead to the establishment of, new function.
About this Structure
1T97 is a Single protein structure of sequence from Bacteriophage t4. Active as Lysozyme, with EC number 3.2.1.17 Full crystallographic information is available from OCA.
Reference
Use of sequence duplication to engineer a ligand-triggered, long-distance molecular switch in T4 lysozyme., Yousef MS, Baase WA, Matthews BW, Proc Natl Acad Sci U S A. 2004 Aug 10;101(32):11583-6. Epub 2004 Jul 30. PMID:15286283
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