The enzyme function initiative

John Alan Gerlt, Karen N. Allen, Steven C. Almo, Richard N. Armstrong, Patricia C. Babbitt, John E Cronan, Debra Dunaway-Mariano, Heidi J Imker, Matthew P. Jacobson, Wladek Minor, C. Dale Poulter, Frank M. Raushel, Andrej Sali, Brian K. Shoichet, Jonathan V Sweedler

Research output: Contribution to journalReview article

Abstract

The Enzyme Function Initiative (EFI) was recently established to address the challenge of assigning reliable functions to enzymes discovered in bacterial genome projects; in this Current Topic, we review the structure and operations of the EFI. The EFI includes the Superfamily/Genome, Protein, Structure, Computation, and Data/Dissemination Cores that provide the infrastructure for reliably predicting the in vitro functions of unknown enzymes. The initial targets for functional assignment are selected from five functionally diverse superfamilies (amidohydrolase, enolase, glutathione transferase, haloalkanoic acid dehalogenase, and isoprenoid synthase), with five superfamily specific Bridging Projects experimentally testing the predicted in vitro enzymatic activities. The EFI also includes the Microbiology Core that evaluates the in vivo context of in vitro enzymatic functions and confirms the functional predictions of the EFI. The deliverables of the EFI to the scientific community include (1) development of a large-scale, multidisciplinary sequence/structure- based strategy for functional assignment of unknown enzymes discovered in genome projects (target selection, protein production, structure determination, computation, experimental enzymology, microbiology, and structure-based annotation), (2) dissemination of the strategy to the community via publications, collaborations, workshops, and symposia, (3) computational and bioinformatic tools for using the strategy, (4) provision of experimental protocols and/or reagents for enzyme production and characterization, and (5) dissemination of data via the EFI's Website, http://enzymefunction.org. The realization of multidisciplinary strategies for functional assignment will begin to define the full metabolic diversity that exists in nature and will impact basic biochemical and evolutionary understanding, as well as a wide range of applications of central importance to industrial, medicinal, and pharmaceutical efforts.

Original languageEnglish (US)
Pages (from-to)9950-9962
Number of pages13
JournalBiochemistry
Volume50
Issue number46
DOIs
StatePublished - Nov 22 2011

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Enzymes
Microbiology
Genes
Amidohydrolases
Genome
Bacterial Genomes
Phosphopyruvate Hydratase
Terpenes
Bioinformatics
Glutathione Transferase
Computational Biology
Publications
Websites
Proteins
Education
Network protocols
Acids
Testing
Pharmaceutical Preparations
In Vitro Techniques

ASJC Scopus subject areas

  • Biochemistry

Cite this

Gerlt, J. A., Allen, K. N., Almo, S. C., Armstrong, R. N., Babbitt, P. C., Cronan, J. E., ... Sweedler, J. V. (2011). The enzyme function initiative. Biochemistry, 50(46), 9950-9962. https://doi.org/10.1021/bi201312u

The enzyme function initiative. / Gerlt, John Alan; Allen, Karen N.; Almo, Steven C.; Armstrong, Richard N.; Babbitt, Patricia C.; Cronan, John E; Dunaway-Mariano, Debra; Imker, Heidi J; Jacobson, Matthew P.; Minor, Wladek; Poulter, C. Dale; Raushel, Frank M.; Sali, Andrej; Shoichet, Brian K.; Sweedler, Jonathan V.

In: Biochemistry, Vol. 50, No. 46, 22.11.2011, p. 9950-9962.

Research output: Contribution to journalReview article

Gerlt, JA, Allen, KN, Almo, SC, Armstrong, RN, Babbitt, PC, Cronan, JE, Dunaway-Mariano, D, Imker, HJ, Jacobson, MP, Minor, W, Poulter, CD, Raushel, FM, Sali, A, Shoichet, BK & Sweedler, JV 2011, 'The enzyme function initiative', Biochemistry, vol. 50, no. 46, pp. 9950-9962. https://doi.org/10.1021/bi201312u
Gerlt JA, Allen KN, Almo SC, Armstrong RN, Babbitt PC, Cronan JE et al. The enzyme function initiative. Biochemistry. 2011 Nov 22;50(46):9950-9962. https://doi.org/10.1021/bi201312u
Gerlt, John Alan ; Allen, Karen N. ; Almo, Steven C. ; Armstrong, Richard N. ; Babbitt, Patricia C. ; Cronan, John E ; Dunaway-Mariano, Debra ; Imker, Heidi J ; Jacobson, Matthew P. ; Minor, Wladek ; Poulter, C. Dale ; Raushel, Frank M. ; Sali, Andrej ; Shoichet, Brian K. ; Sweedler, Jonathan V. / The enzyme function initiative. In: Biochemistry. 2011 ; Vol. 50, No. 46. pp. 9950-9962.
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