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Literature DB >> 8378307

Engineering multiple properties of a protein by combinatorial mutagenesis.

Abstract

A method for simultaneously engineering multiple properties of a protein, based on the observed additivity of effects of individual mutations, is presented. We show that, for the gene V protein of bacteriophage f1, effects of double mutations on both protein stability and DNA binding affinity are approximately equal to the sums of the effects of the constituent single mutations. This additivity of effects implies that it is possible to deliberately construct mutant proteins optimized for multiple properties by combination of appropriate single mutations chosen from a characterized library.

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Year: 1993 PMID： 8378307 PMCID： PMC47357 DOI： 10.1073/pnas.90.18.8367

Source DB: PubMed Journal: Proc Natl Acad Sci U S A ISSN： 0027-8424 Impact factor: 11.205

42 in total

1. Designing substrate specificity by protein engineering of electrostatic interactions.

Authors: J A Wells; D B Powers; R R Bott; T P Graycar; D A Estell
Journal: Proc Natl Acad Sci U S A Date: 1987-03 Impact factor: 11.205

2. Fine structure of a membrane anchor domain.

Authors: N G Davis; J D Boeke; P Model
Journal: J Mol Biol Date: 1985-01-05 Impact factor: 5.469

3. Rational modification of enzyme catalysis by engineering surface charge.

Authors: A J Russell; A R Fersht
Journal: Nature Date: 1987 Aug 6-12 Impact factor: 49.962

4. Proteases of enhanced stability: characterization of a thermostable variant of subtilisin.

Authors: P N Bryan; M L Rollence; M W Pantoliano; J Wood; B C Finzel; G L Gilliland; A J Howard; T L Poulos
Journal: Proteins Date: 1986-12

5. Contributions of hydrogen bonds of Thr 157 to the thermodynamic stability of phage T4 lysozyme.

Authors: T Alber; D P Sun; K Wilson; J A Wozniak; S P Cook; B W Matthews
Journal: Nature Date: 1987 Nov 5-11 Impact factor: 49.962

6. Disulfide bonds and thermal stability in T4 lysozyme.

Authors: R Wetzel; L J Perry; W A Baase; W J Becktel
Journal: Proc Natl Acad Sci U S A Date: 1988-01 Impact factor: 11.205

7. Dissecting the catalytic triad of a serine protease.

Authors: P Carter; J A Wells
Journal: Nature Date: 1988-04-07 Impact factor: 49.962

8. Recruitment of substrate-specificity properties from one enzyme into a related one by protein engineering.

Authors: J A Wells; B C Cunningham; T P Graycar; D A Estell
Journal: Proc Natl Acad Sci U S A Date: 1987-08 Impact factor: 11.205

9. Engineering enzyme specificity by "substrate-assisted catalysis".

Authors: P Carter; J A Wells
Journal: Science Date: 1987-07-24 Impact factor: 47.728

10. Stabilization of lambda repressor against thermal denaturation by site-directed Gly----Ala changes in alpha-helix 3.

Authors: M H Hecht; J M Sturtevant; R T Sauer
Journal: Proteins Date: 1986-09

21 in total

1. New insight into long-range nonadditivity within protein double-mutant cycles.

Authors: Andrei Y Istomin; M Michael Gromiha; Oleg K Vorov; Donald J Jacobs; Dennis R Livesay
Journal: Proteins Date: 2008-02-15

2. Potential use of additivity of mutational effects in simplifying protein engineering.

Authors: M M Skinner; T C Terwilliger
Journal: Proc Natl Acad Sci U S A Date: 1996-10-01 Impact factor: 11.205

3. Studies using double mutants of the conformational transitions in influenza hemagglutinin required for its membrane fusion activity.

Authors: D A Steinhauer; J Martín; Y P Lin; S A Wharton; M B Oldstone; J J Skehel; D C Wiley
Journal: Proc Natl Acad Sci U S A Date: 1996-11-12 Impact factor: 11.205

Engineering multiple properties of a protein by combinatorial mutagenesis.

1. Designing substrate specificity by protein engineering of electrostatic interactions.

2. Fine structure of a membrane anchor domain.

3. Rational modification of enzyme catalysis by engineering surface charge.

4. Proteases of enhanced stability: characterization of a thermostable variant of subtilisin.

5. Contributions of hydrogen bonds of Thr 157 to the thermodynamic stability of phage T4 lysozyme.

6. Disulfide bonds and thermal stability in T4 lysozyme.

7. Dissecting the catalytic triad of a serine protease.

8. Recruitment of substrate-specificity properties from one enzyme into a related one by protein engineering.

9. Engineering enzyme specificity by "substrate-assisted catalysis".

10. Stabilization of lambda repressor against thermal denaturation by site-directed Gly----Ala changes in alpha-helix 3.

1. New insight into long-range nonadditivity within protein double-mutant cycles.

2. Potential use of additivity of mutational effects in simplifying protein engineering.

3. Studies using double mutants of the conformational transitions in influenza hemagglutinin required for its membrane fusion activity.

4. Stepwise in vitro affinity maturation of Vitaxin, an alphav beta3-specific humanized mAb.

5. Inferring the shape of global epistasis.

6. Biophysical Inference of Epistasis and the Effects of Mutations on Protein Stability and Function.

7. sw ApoMb Amyloid Aggregation under Nondenaturing Conditions: The Role of Native Structure Stability.

Review 8. Conformational stability of dimeric proteins: quantitative studies by equilibrium denaturation.

9. Modification of the substrate specificity of an acyl-acyl carrier protein thioesterase by protein engineering.

10. Inferring stabilizing mutations from protein phylogenies: application to influenza hemagglutinin.