Target selection and annotation for the structural genomics of the amidohydrolase and enolase superfamilies

Ursula Pieper, Ranyee Chiang, Jennifer J. Seffernick, Shoshana D. Brown, Margaret E. Glasner, Libusha Kelly, Narayanan Eswar, J. Michael Sauder, Jeffrey B. Bonanno, Subramanyam Swaminathan, Stephen K. Burley, Xiaojing Zheng, Mark R. Chance, Steven C. Almo, John Alan Gerlt, Frank M. Raushel, Matthew P. Jacobson, Patricia C. Babbitt, Andrej Sali

Research output: Contribution to journalArticle

Abstract

To study the substrate specificity of enzymes, we use the amidohydrolase and enolase superfamilies as model systems; members of these superfamilies share a common TIM barrel fold and catalyze a wide range of chemical reactions. Here, we describe a collaboration between the Enzyme Specificity Consortium (ENSPEC) and the New York SGX Research Center for Structural Genomics (NYSGXRC) that aims to maximize the structural coverage of the amidohydrolase and enolase superfamilies. Using sequence- and structure-based protein comparisons, we first selected 535 target proteins from a variety of genomes for high-throughput structure determination by X-ray crystallography; 63 of these targets were not previously annotated as superfamily members. To date, 20 unique amidohydrolase and 41 unique enolase structures have been determined, increasing the fraction of sequences in the two superfamilies that can be modeled based on at least 30% sequence identity from 45% to 73%. We present case studies of proteins related to uronate isomerase (an amidohydrolase superfamily member) and mandelate racemase (an enolase superfamily member), to illustrate how this structure-focused approach can be used to generate hypotheses about sequence-structure-function relationships.

Original languageEnglish (US)
Pages (from-to)107-125
Number of pages19
JournalJournal of Structural and Functional Genomics
Volume10
Issue number2
DOIs
StatePublished - Apr 1 2009

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Amidohydrolases
Phosphopyruvate Hydratase
Genomics
mandelate racemase
Isomerases
Proteins
X ray crystallography
X Ray Crystallography
Enzymes
Substrate Specificity
Chemical reactions
Genes
Throughput
Genome
Substrates
Research

Keywords

  • Amidohydrolase and enolase superfamilies
  • Structural genomics
  • Structure annotation
  • Target selection

ASJC Scopus subject areas

  • Structural Biology
  • Biochemistry
  • Genetics

Cite this

Target selection and annotation for the structural genomics of the amidohydrolase and enolase superfamilies. / Pieper, Ursula; Chiang, Ranyee; Seffernick, Jennifer J.; Brown, Shoshana D.; Glasner, Margaret E.; Kelly, Libusha; Eswar, Narayanan; Sauder, J. Michael; Bonanno, Jeffrey B.; Swaminathan, Subramanyam; Burley, Stephen K.; Zheng, Xiaojing; Chance, Mark R.; Almo, Steven C.; Gerlt, John Alan; Raushel, Frank M.; Jacobson, Matthew P.; Babbitt, Patricia C.; Sali, Andrej.

In: Journal of Structural and Functional Genomics, Vol. 10, No. 2, 01.04.2009, p. 107-125.

Research output: Contribution to journalArticle

Pieper, U, Chiang, R, Seffernick, JJ, Brown, SD, Glasner, ME, Kelly, L, Eswar, N, Sauder, JM, Bonanno, JB, Swaminathan, S, Burley, SK, Zheng, X, Chance, MR, Almo, SC, Gerlt, JA, Raushel, FM, Jacobson, MP, Babbitt, PC & Sali, A 2009, 'Target selection and annotation for the structural genomics of the amidohydrolase and enolase superfamilies', Journal of Structural and Functional Genomics, vol. 10, no. 2, pp. 107-125. https://doi.org/10.1007/s10969-008-9056-5
Pieper, Ursula ; Chiang, Ranyee ; Seffernick, Jennifer J. ; Brown, Shoshana D. ; Glasner, Margaret E. ; Kelly, Libusha ; Eswar, Narayanan ; Sauder, J. Michael ; Bonanno, Jeffrey B. ; Swaminathan, Subramanyam ; Burley, Stephen K. ; Zheng, Xiaojing ; Chance, Mark R. ; Almo, Steven C. ; Gerlt, John Alan ; Raushel, Frank M. ; Jacobson, Matthew P. ; Babbitt, Patricia C. ; Sali, Andrej. / Target selection and annotation for the structural genomics of the amidohydrolase and enolase superfamilies. In: Journal of Structural and Functional Genomics. 2009 ; Vol. 10, No. 2. pp. 107-125.
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