1lyg

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1lyg, resolution 1.8Å

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DISSECTION OF HELIX CAPPING IN T4 LYSOZYME BY STRUCTURAL AND THERMODYNAMIC ANALYSIS OF SIX AMINO ACID SUBSTITUTIONS AT THR 59

Overview

Threonine 59, a helix-capping residue at the amino terminus of the longest, helix in T4 phage lysozyme, was substituted with valine, alanine, glycine, serine, asparagine, and aspartic acid. The valine, alanine, and glycine, replacements were observed to be somewhat more destabilizing than serine, asparagine, and aspartic acid. The crystal structures of the different, variants showed that changes in conformation occurred at the site of, substitution, including Asp 61, which is nearby, as well as displacement, of a solvent molecule that is hydrogen-bonded to the gamma-oxygen of Thr, 59 in wild-type lysozyme. Neither the structures nor the stabilities of, the mutant proteins support the hypothesis of Serrano and Fersht (1989), that glycine and alanine are better helix-capping residues than valine, because a smaller-sized residue allows better hydration at the end of the, helix. In the aspartic acid and asparagine replacements the substituted, side chains form hydrogen bonds with the end of the helix, as does, threonine and serine at this position. In contrast, however, the Asp and, Asn side chains also make unusually close contacts with carbon atoms in, Asp 61. This suggests a structural basis for the heretofore puzzling, observations that asparagine is more frequently observed as a, helix-capping residue than threonine [Richardson, J. S., & Richardson, D., C. (1988) Science 240, 1648-1652] yet Thr----Asn replacements at N-cap, positions in barnase were found to be destabilizing [Serrano, L., &, Fersht, A. R. (1989) Nature 342, 296-299].(ABSTRACT TRUNCATED AT 250, WORDS)

About this Structure

1LYG is a Single protein structure of sequence from Enterobacteria phage t2 with CL and BME as ligands. Full crystallographic information is available from OCA.

Reference

Dissection of helix capping in T4 lysozyme by structural and thermodynamic analysis of six amino acid substitutions at Thr 59., Bell JA, Becktel WJ, Sauer U, Baase WA, Matthews BW, Biochemistry. 1992 Apr 14;31(14):3590-6. PMID:1567817

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