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Conversion of a maltose receptor into a zinc biosensor by computational design.

Publication ,  Journal Article
Marvin, JS; Hellinga, HW
Published in: Proc Natl Acad Sci U S A
April 24, 2001

We have demonstrated that it is possible to radically change the specificity of maltose binding protein by converting it into a zinc sensor using a rational design approach. In this new molecular sensor, zinc binding is transduced into a readily detected fluorescence signal by use of an engineered conformational coupling mechanism linking ligand binding to reporter group response. An iterative progressive design strategy led to the construction of variants with increased zinc affinity by combining binding sites, optimizing the primary coordination sphere, and exploiting conformational equilibria. Intermediates in the design series show that the adaptive process involves both introduction and optimization of new functions and removal of adverse vestigial interactions. The latter demonstrates the importance of the rational design approach in uncovering cryptic phenomena in protein function, which cannot be revealed by the study of naturally evolved systems.

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Published In

Proc Natl Acad Sci U S A

DOI

ISSN

0027-8424

Publication Date

April 24, 2001

Volume

98

Issue

9

Start / End Page

4955 / 4960

Location

United States

Related Subject Headings

  • Zinc
  • Thermodynamics
  • Temperature
  • Substrate Specificity
  • Software
  • Signal Transduction
  • Protein Engineering
  • Protein Conformation
  • Mutation
  • Models, Molecular
 

Citation

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Marvin, J. S., & Hellinga, H. W. (2001). Conversion of a maltose receptor into a zinc biosensor by computational design. Proc Natl Acad Sci U S A, 98(9), 4955–4960. https://doi.org/10.1073/pnas.091083898
Marvin, J. S., and H. W. Hellinga. “Conversion of a maltose receptor into a zinc biosensor by computational design.Proc Natl Acad Sci U S A 98, no. 9 (April 24, 2001): 4955–60. https://doi.org/10.1073/pnas.091083898.
Marvin JS, Hellinga HW. Conversion of a maltose receptor into a zinc biosensor by computational design. Proc Natl Acad Sci U S A. 2001 Apr 24;98(9):4955–60.
Marvin, J. S., and H. W. Hellinga. “Conversion of a maltose receptor into a zinc biosensor by computational design.Proc Natl Acad Sci U S A, vol. 98, no. 9, Apr. 2001, pp. 4955–60. Pubmed, doi:10.1073/pnas.091083898.
Marvin JS, Hellinga HW. Conversion of a maltose receptor into a zinc biosensor by computational design. Proc Natl Acad Sci U S A. 2001 Apr 24;98(9):4955–4960.
Journal cover image

Published In

Proc Natl Acad Sci U S A

DOI

ISSN

0027-8424

Publication Date

April 24, 2001

Volume

98

Issue

9

Start / End Page

4955 / 4960

Location

United States

Related Subject Headings

  • Zinc
  • Thermodynamics
  • Temperature
  • Substrate Specificity
  • Software
  • Signal Transduction
  • Protein Engineering
  • Protein Conformation
  • Mutation
  • Models, Molecular