Exploiting the right side of the ramachandran plot: Substitution of glycines by D-alanine can significantly increase protein stability

被引：71

作者：

Anil, B

Song, BB

Tang, YF

Raleigh, DP ^{[1
]}

机构：

[1] SUNY Stony Brook, Dept Chem, Stony Brook, NY 11794 USA

[2] SUNY Stony Brook, Grad Programs Biophys & Biochem & Struct Biol, Stony Brook, NY 11794 USA

来源：

JOURNAL OF THE AMERICAN CHEMICAL SOCIETY | 2004年 / 126卷 / 41期

关键词：

D O I：

10.1021/ja047119i

中图分类号：

O6 [化学];

学科分类号：

0703 ;

摘要：

A major goal of protein engineering is the enhancement of protein stability. Here we demonstrate a rational method for enhancing the stability of globular proteins by targeting glycine residues which adopt conformations with Φ > 0. Replacement of such a glycine by d-alanine can lead to a significant increase in stability. The approach is tested at three sites in two model proteins. NMR and CD indicated that the substitutions do not alter the structure. Replacement of glycine-24 of the N-terminal domain of L9 (NTL9) with d-Ala results in an increase in stability of 1.3 kcal mol-1, while replacement of glycine-34 of NTL9 leads to an increase of 1.9 kcal mol-1. Replacement of glycine-331 of the UBA domain with d-Ala leads to an increase in stability of 0.6 kcal mol-1. Copyright © 2004 American Chemical Society.

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页码：13194 / 13195

页数：2

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共 34 条

[1] Protein prosthesis:: A nonnatural residue accelerates folding and increases stability [J].

Arnold, U ;

Hinderaker, MP ;

Köditz, J ;

Golbik, R ;

Ulbrich-Hofmann, R ;

Raines, RT .

JOURNAL OF THE AMERICAN CHEMICAL SOCIETY, 2003, 125 (25) :7500-7501

[2] Protein prosthesis:: A semisynthetic enzyme with a β-peptide reverse turn [J].

Arnold, U ;

Hinderaker, MP ;

Nilsson, BL ;

Huck, BR ;

Gellman, SH ;

Raines, RT .

JOURNAL OF THE AMERICAN CHEMICAL SOCIETY, 2002, 124 (29) :8522-8523

[3] A coiled coil with a fluorous core [J].

Bilgiçer, B ;

Fichera, A ;

Kumar, K .

JOURNAL OF THE AMERICAN CHEMICAL SOCIETY, 2001, 123 (19) :4393-4399

[4] The interrelationships of side-chain and main-chain conformations in proteins [J].

Chakrabarti, P ;

Pal, D .

PROGRESS IN BIOPHYSICS & MOLECULAR BIOLOGY, 2001, 76 (1-2) :1-102

[5] SYNTHESIS OF PROTEINS BY NATIVE CHEMICAL LIGATION [J].

DAWSON, PE ;

MUIR, TW ;

CLARKLEWIS, I ;

KENT, SBH .

SCIENCE, 1994, 266 (5186) :776-779

[6] Structure of a human DNA repair protein UBA domain that interacts with HIV-1 Vpr [J].

Dieckmann, T ;

Withers-Ward, ES ;

Jarosinski, MA ;

Liu, CF ;

Chen, ISY ;

Feigon, J .

NATURE STRUCTURAL BIOLOGY, 1998, 5 (12) :1042-1047

[7] GLYCINE TO ALANINE SUBSTITUTIONS IN HELICES OF GLYCERALDEHYDE-3-PHOSPHATE DEHYDROGENASE - EFFECTS ON STABILITY [J].

GANTER, C ;

PLUCKTHUN, A .

BIOCHEMISTRY, 1990, 29 (40) :9395-9402

[8] Insights on beta-hairpin stability in aqueous solution from peptides with enforced type I' and type II' beta-turns [J].

Haque, TS ;

Gellman, SH .

JOURNAL OF THE AMERICAN CHEMICAL SOCIETY, 1997, 119 (09) :2303-2304

[9] Φ-Values beyond the ribosomally encoded amino acids:: Kinetic and thermodynamic consequences of incorporating trifluoromethyl amino acids in a globular protein [J].

Horng, JC ;

Raleigh, DP .

JOURNAL OF THE AMERICAN CHEMICAL SOCIETY, 2003, 125 (31) :9286-9287

[10] Conformations of amino acids in proteins [J].

Hovmöller, S ;

Zhou, T ;

Ohlson, T .

ACTA CRYSTALLOGRAPHICA SECTION D-BIOLOGICAL CRYSTALLOGRAPHY, 2002, 58 :768-776

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