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

Journal Article

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.

Full Text

Duke Authors

Cited Authors

  • Marvin, JS; Hellinga, HW

Published Date

  • April 24, 2001

Published In

Volume / Issue

  • 98 / 9

Start / End Page

  • 4955 - 4960

PubMed ID

  • 11320244

International Standard Serial Number (ISSN)

  • 0027-8424

Digital Object Identifier (DOI)

  • 10.1073/pnas.091083898

Language

  • eng

Conference Location

  • United States