The structure/function relationship of a dual-substrate (βα)8-isomerase

Helena Wright, Lianet Noda-García, Adrián Ochoa-Leyva, David A. Hodgson, Vilmos Fülöp, Francisco Barona-Gómez*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

18 Scopus citations


Two structures of phosphoribosyl isomerase A (PriA) from Streptomyces coelicolor, involved in both histidine and tryptophan biosynthesis, were solved at 1.8 Å resolution. A closed conformer was obtained, which represents the first complete structure of PriA, revealing hitherto unnoticed molecular interactions and the occurrence of conformational changes. Inspection of these conformers, including ligand-docking simulations, allowed identification of residues involved in substrate recognition, chemical catalysis and conformational changes. These predictions were validated by mutagenesis and functional analysis. Arg19 and Ser81 were shown to play critical roles within the carboxyl and amino phosphate-binding sites, respectively; the catalytic residues Asp11 and Asp130 are responsible for both activities; and Thr166 and Asp171, which make an unusual contact, are likely to elicit the conformational changes needed for adopting the active site architectures. This represents the first report of the structure/function relationship of this (βα)8-isomerase.

Original languageAmerican English
Pages (from-to)16-21
Number of pages6
JournalBiochemical and Biophysical Research Communications
Issue number1
StatePublished - 4 Jan 2008
Externally publishedYes

Bibliographical note

Funding Information:
This work was funded by CONACyT, Mexico (Project No. 50952-Q) and the Royal Society, UK (Project No. 20060612184333-3475-43146). We are grateful to Filiberto Sánchez, Paul Gaytan and Jorge Yañez for technical assistance and the European Synchrotron Radiation Facility (ESRF) for access and user support.


  • (βα)-Barrel
  • Co-occurrence of conformers
  • HisA
  • PriA
  • TrpF


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