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Arabinose 5-phosphate covalently inhibits transaldolase

  • Samuel H. Light
  • Wayne F. AndersonEmail author
Article

Abstract

Arabinose 5-phosphate (A5P) is the aldopentose version of the ketohexose fructose 6-phosphate (F6P), having identical stereochemistry but lacking atoms corresponding to the 1-carbon and 1-hydroxyl. Despite structural similarity and conservation of the reactive portion of F6P, F6P acts as a substrate whereas A5P is reported to be an inhibitor of transaldolase. To address the lack of A5P reactivity we determined a crystal structure of the Francisella tularensis transaldolase in complex with A5P. This structure reveals that like F6P, A5P forms a covalent Schiff base with active site Lys135. Unlike F6P, A5P binding fails to displace an ordered active site water molecule. Retaining this water necessitates conformational changes at the A5P-protein linkage that possibly hinder reactivity. The findings presented here show the basis of A5P inhibition and suggest an unusual mechanism of competitive, reversible-covalent transaldolase regulation.

Keywords

Arabinose 5-phosphate Competitive inhibition Glucose 6-phosphate Ordered water Pentose phosphate pathway X-ray crystal structure 

Abbreviations

A5P

Arabinose 5-phosphate

E4P

Erythrose 4-phosphate

F6P

Fructose 6-phosphate

G3P

Glyceraldehyde 3-phosphate

S7P

Sedoheptulose 7-phosphate

Notes

Acknowledgments

The Center for Structural Genomics of Infectious Diseases has been funded in whole or in part with federal funds from the National Institute of Allergy and Infectious Diseases, National Institutes of Health, Department of Health and Human Services, under Contract Nos. HHSN272200700058C and HHSN272201200026C (to W.F.A). Use of the Advanced Photon Source was supported by the U. S. Department of Energy, Office of Science, Office of Basic Energy Sciences, under Contract No. DE-AC02-06CH11357. Use of the LS-CAT Sector 21 was supported by the Michigan Economic Development Corporation and the Michigan Technology Tri-Corridor for the support of this research program (Grant 085P1000817).

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Copyright information

© Springer Science+Business Media Dordrecht 2014

Authors and Affiliations

  1. 1.Center for Structural Genomics of Infectious Diseases, Department of Molecular Pharmacology and Biological Chemistry, Feinberg School of MedicineNorthwestern UniversityChicagoUSA

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