1ab5

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STRUCTURE OF CHEY MUTANT F14N, V21T

File:1ab5.gif


1ab5, resolution 2.40Å

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OverviewOverview

The crystal structures of two double mutants (F14N/V21T and F14N/V86T) of, the signal transduction protein CheY have been determined to a resolution, of 2.4 and 2.2 A, respectively. The structures were solved by molecular, replacement and refined to final R values of 18.4 and 19.2%, respectively., Together with urea-denaturation experiments the structures have been used, to analyse the effects of mutations where hydrophobic residues are, replaced by residues capable of establishing hydrogen bonds. The large, increase in stabilization (-12.1 kJ mol-1) of the mutation Phe14Asn arises, from two factors: a reverse hydrophobic effect and the formation of a good, N-cap at alpha-helix 1. In addition, a forward-backward hydrogen-bonding, pattern, resembling an N-capping box and involving Asn14 and Arg18, has, been found. The two Val to Thr mutations at the hydrophobic core have, different thermodynamic effects: the mutation Val21Thr does not affect the, stability of the protein while the mutation Val86Thr causes a small, destabilization of 1.7 kJ mol-1. At site 21 a backward side, chain-to-backbone hydrogen bond is formed inside alpha-helix 1 with the, carbonyl O atom of the i - 4 residue without movement of the mutated side, chain. The destabilizing effect of introducing a polar group in the core, is efficiently compensated for by the formation of an extra hydrogen bond., At site 86 the new Ogamma atom escapes from the hydrophobic environment by, a chi1 rotation into an adjacent hydrophilic cavity to form a new hydrogen, bond. In this case the isosteric Val to Thr substitution is disruptive but, the loss in stabilization energy is partly compensated by the formation of, a hydrogen bond. The two crystal structures described in this work, underline the significance of the hydrogen-bond component to protein, stability.

About this StructureAbout this Structure

1AB5 is a Single protein structure of sequence from Escherichia coli. Full crystallographic information is available from OCA.

ReferenceReference

Structure analysis of two CheY mutants: importance of the hydrogen-bond contribution to protein stability., Wilcock D, Pisabarro MT, Lopez-Hernandez E, Serrano L, Coll M, Acta Crystallogr D Biol Crystallogr. 1998 May 1;54(Pt 3):378-85. PMID:9761905

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