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 A. Gerlt, Frank M. Raushel, Matthew P. Jacobson, Patricia C. Babbitt, Andrej Sali

Research output: Contribution to journalArticlepeer-review

24 Scopus citations


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
Issue number2
StatePublished - Apr 2009


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

ASJC Scopus subject areas

  • Structural Biology
  • Biochemistry
  • Genetics


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