1qry

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(New page: 200px<br /><applet load="1qry" size="450" color="white" frame="true" align="right" spinBox="true" caption="1qry" /> '''Homeobox protein VND (ventral nervous system...)
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Revision as of 22:48, 20 November 2007


1qry

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Homeobox protein VND (ventral nervous system defective protein)

Overview

The three-dimensional solution structure obtained by NMR of the A35T, mutant vnd/NK-2 homeodomain bound to the vnd/NK-2 consensus 16 bp DNA, sequence was determined. This mutation to threonine from alanine in, position 35 in helix II of the vnd/NK-2 homeodomain is associated with, early embryonic lethality in Drosophila melanogaster. Although the unbound, mutant protein is not structured, in the DNA-bound state it adopts the, three-helix fold characteristic of all known homeodomains, but with, alterations relative to the structure of the wild-type analogue. These, structural modifications occur, and are accompanied by a 50-fold reduction, in the DNA binding affinity, even though most of the protein-DNA, interactions originally seen for the wild-type homeodomain are found, likewise in the threonine analogue. Alterations include torsional angle, changes in the loop between helix I and helix II, and in the turn between, helix II and helix III, as well as in a distortion of the usual, antiparallel orientation of helix I with respect to helix II. The, alteration of the position of leucine 40 in the A35T mutant is proposed to, explain the observed 1.27 ppm upfield shift of the corresponding amide, proton resonance relative to the value observed for the wild-type, analogue. A detailed comparison of the structures of the mutant A35T and, wild-type vnd/NK-2 homeodomains bound to the cognate DNA is presented. The, consequences of the structural alteration of the DNA-bound A35T mutant, vnd/NK-2 protein may constitute the basis of the observed early embryonic, lethality.

About this Structure

1QRY is a Single protein structure of sequence from Drosophila melanogaster. Full crystallographic information is available from OCA.

Reference

Distortion of the three-dimensional structure of the vnd/NK-2 homeodomain bound to DNA induced by an embryonically lethal A35T point mutation., Hwang KJ, Xiang B, Gruschus JM, Nam KY, No KT, Nirenberg M, Ferretti JA, Biochemistry. 2003 Nov 4;42(43):12522-31. PMID:14580198

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