The crystal structure of shikimate dehydrogenase (AroE) reveals a unique NADPH binding mode

J Bacteriol. 2003 Jul;185(14):4144-51. doi: 10.1128/JB.185.14.4144-4151.2003.


Shikimate dehydrogenase catalyzes the NADPH-dependent reversible reduction of 3-dehydroshikimate to shikimate. We report the first X-ray structure of shikimate dehydrogenase from Haemophilus influenzae to 2.4-A resolution and its complex with NADPH to 1.95-A resolution. The molecule contains two domains, a catalytic domain with a novel open twisted alpha/beta motif and an NADPH binding domain with a typical Rossmann fold. The enzyme contains a unique glycine-rich P-loop with a conserved sequence motif, GAGGXX, that results in NADPH adopting a nonstandard binding mode with the nicotinamide and ribose moieties disordered in the binary complex. A deep pocket with a narrow entrance between the two domains, containing strictly conserved residues primarily contributed by the catalytic domain, is identified as a potential 3-dehydroshikimate binding pocket. The flexibility of the nicotinamide mononucleotide portion of NADPH may be necessary for the substrate 3-dehydroshikimate to enter the pocket and for the release of the product shikimate.

Publication types

  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Alcohol Oxidoreductases / chemistry*
  • Alcohol Oxidoreductases / metabolism
  • Amino Acid Sequence
  • Binding Sites
  • Catalytic Domain
  • Crystallography, X-Ray
  • Haemophilus influenzae / enzymology*
  • Humans
  • Models, Molecular
  • Molecular Sequence Data
  • NADP / metabolism*
  • Protein Conformation
  • Protein Structure, Tertiary
  • Sequence Alignment
  • Shikimic Acid / analogs & derivatives*
  • Shikimic Acid / metabolism


  • 3-dehydroshikimate
  • Shikimic Acid
  • NADP
  • Alcohol Oxidoreductases
  • Shikimate dehydrogenase