Context-dependent protein stabilization by methionine-to-leucine substitution shown in T4 lysozyme

Protein Science : a Publication of the Protein Society
L A LipscombB W Matthews

Abstract

The substitution of methionines with leucines within the interior of a protein is expected to increase stability both because of a more favorable solvent transfer term as well as the reduced entropic cost of holding a leucine side chain in a defined position. Together, these two terms are expected to contribute about 1.4 kcal/mol to protein stability for each Met --> Leu substitution when fully buried. At the same time, this expected beneficial effect may be offset by steric factors due to differences in the shape of leucine and methionine. To investigate the interplay between these factors, all methionines in T4 lysozyme except at the amino-terminus were individually replaced with leucine. Of these mutants, M106L and M120L have stabilities 0.5 kcal/mol higher than wild-type T4 lysozyme, while M6L is significantly destabilized (-2.8 kcal/mol). M102L, described previously, is also destabilized (-0.9 kcal/mol). Based on this limited sample it appears that methionine-to-leucine substitutions can increase protein stability but only in a situation where the methionine side chain is fully or partially buried, yet allows the introduction of the leucine without concomitant steric interference. The variants, together with methionine-to-...Continue Reading

References

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Citations

May 27, 2005·Journal of Medicinal Chemistry·Alan P GravesBrian K Shoichet
May 20, 2009·Proceedings of the National Academy of Sciences of the United States of America·Giselle Román-HernándezTania A Baker
Sep 22, 2001·Journal of Biomolecular Structure & Dynamics·D Pal, P Chakrabarti
Jan 11, 2001·Protein Science : a Publication of the Protein Society·J M WordD C Richardson
Nov 26, 2011·Science·Ruei-Jiun HungJonathan R Terman
Jan 28, 2004·Bioscience, Biotechnology, and Biochemistry·Jureerut PooartTomohiro Araki
Jul 27, 2002·Protein Science : a Publication of the Protein Society·Andrei L LomizeIrina D Pogozheva
Apr 23, 2009·Protein Science : a Publication of the Protein Society·Blaine H M MooersBrian W Matthews
Sep 10, 2003·Journal of Molecular Biology·Blaine H M MooersBrian W Matthews
Jan 23, 2010·Protein Science : a Publication of the Protein Society·Walter A BaaseBrian W Matthews
Feb 17, 2009·Biophysical Journal·Aaron P YamniukHans J Vogel
Nov 11, 2008·Molecular Cell·Kevin H WangTania A Baker
Apr 22, 2015·PloS One·Kwame A Darfour-OduroLawrence B Schook
Sep 17, 2004·Biopolymers·Gavin A Manderson, Jonas S Johansson
May 25, 1999·FEBS Letters·K DüringW Gieffers
Feb 13, 2014·Chemphyschem : a European Journal of Chemical Physics and Physical Chemistry·Ramkrishna AdhikaryFloyd E Romesberg
Sep 4, 2018·Protein Science : a Publication of the Protein Society·Ryan L HayesCharles L Brooks
Jun 16, 2017·BMC Bioinformatics·Wen Torng, Russ B Altman
Nov 17, 2016·Scientifica·Gülşah P ÖzgünNevin Gül Karagüler
Oct 20, 2017·Epigenetics & Chromatin·Saikat BhattacharyaSanjay Gupta
Oct 27, 2018·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Peta J HarveyDavid J Craik
May 12, 2018·International Journal of Molecular Sciences·Dengming MingHe Huang
Feb 20, 2021·Proceedings of the National Academy of Sciences of the United States of America·Dillon T FloodPhilip E Dawson

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