Using the Structure‐Function Linkage Database to Characterize Functional Domains in Enzymes

Shoshana Brown1, Patricia Babbitt2

1 Department of Bioengineering and Therapeutic Sciences, University of California, San Francisco, California, 2 California Institute for Quantitative Biosciences, University of California, San Francisco, California
Publication Name:  Current Protocols in Bioinformatics
Unit Number:  Unit 2.10
DOI:  10.1002/0471250953.bi0210s48
Online Posting Date:  December, 2014
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The Structure‐Function Linkage Database (SFLD; is a Web‐accessible database designed to link enzyme sequence, structure, and functional information. This unit describes the protocols by which a user may query the database to predict the function of uncharacterized enzymes and to correct misannotated functional assignments. The information in this unit is especially useful in helping a user discriminate functional capabilities of a sequence that is only distantly related to characterized sequences in publicly available databases. © 2014 by John Wiley & Sons, Inc.

Keywords: protein superfamily analysis; protein sequence analysis; structure‐function relationships; protein function prediction; annotation transfer

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Table of Contents

  • Introduction
  • Basic Protocol 1: Using The SFLD to Predict the Function of an Uncharacterized Enzyme
  • Alternate Protocol 1: Using the SFLD to Correct Misannotated Functional Assignments
  • Guidelines for Understanding Results
  • Commentary
  • Figures
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Literature Cited

Literature Cited
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  Babbitt, P.C. and Gerlt, J.A. 1997. Understanding enzyme superfamilies. Chemistry As the fundamental determinant in the evolution of new catalytic activities. J. Biol. Chem. 272:30591‐30594.
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  Gerlt, J.A. and Babbitt, P.C. 2001. Divergent evolution of enzymatic function: Mechanistically diverse superfamilies and functionally distinct suprafamilies. Annu. Rev. Biochem. 70:209‐246.
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Key References
  Akiva et al., 2014. See above.
  Describes the SFLD.
  Gerlt and Babbitt, 2001. See above.
  Describes various mechanisms of enzyme evolution, including chemistry‐driven evolution of mechanistically diverse superfamilies. Several mechanistically diverse superfamilies are discussed in detail.
  Babbitt et al., 1995. See above.
  Describes the use of superfamily analysis to elucidate the function of an uncharacterized ORF in Escherichia coli.
Internet Resources
  The Structure‐Function Linkage Database.
  Get genome context information for a specific gene.
  Get operon context information for a specific gene.
  Get operon context information for a specific gene.
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