UDP-galactopyranose mutase has a novel structure and mechanism

DARS Sanders, AG Staines, SA McMahon, MR McNeil, C Whitfield, James Henderson Naismith

Research output: Contribution to journalLetterpeer-review

150 Citations (Scopus)

Abstract

Uridine diphosphogalactofuranose (UDP-Galf) is the precursor of the D-galactofuranose (Galf) residues found in bacterial and parasitic cell walls, including those of many pathogens, such as Mycobacterium tuberculosis and Trypanosoma cruzi. UDP-Galf is made from UDP-galactopyranose (UDP-Galp) by the enzyme UDP-galactopyranose mutase (mutase). The mutase enzyme is essential for the viability of mycobacteria and is not found in humans, making it a viable therapeutic target. The mechanism by which mutase achieves the unprecedented ring contraction of a nonreducing sugar is unclear. We have solved the crystal structure of Escherichia coli mutase to 2.4 Angstrom resolution. The novel structure shows that the flavin nucleotide is located in a cleft lined with conserved residues. Site-directed mutagenesis studies indicate that this cleft contains the active site, with the sugar ring of the substrate UDP-galactose adjacent to the exposed isoalloxazine ring of FAD. Assay results establish that the enzyme is active only when flavin is reduced. We conclude that mutase most likely functions by transient reduction of substrate.

Original languageEnglish
Pages (from-to)858-863
Number of pages6
JournalNature Structural and Molecular Biology
Volume8
Issue number10
DOIs
Publication statusPublished - Oct 2001

Keywords

  • ESCHERICHIA-COLI
  • ENZYMATIC-SYNTHESIS
  • CRYSTAL-STRUCTURES
  • LEISHMANIA-MAJOR
  • LIPOPHOSPHOGLYCAN
  • GALACTOFURANOSE
  • IDENTIFICATION
  • CATALYSIS
  • REDUCTASE
  • BACTERIA

Fingerprint

Dive into the research topics of 'UDP-galactopyranose mutase has a novel structure and mechanism'. Together they form a unique fingerprint.

Cite this