Crystal structure of shikimate 5-dehydrogenase (SDH) bound to NADP: insights into function and evolution

Structure. 2003 Aug;11(8):1005-13. doi: 10.1016/s0969-2126(03)00159-x.


The crystal structure of Methanococcus jannaschii shikimate 5-dehydrogenase (MjSDH) bound to the cofactor nicotinamide adenine dinucleotide phosphate (NADP) has been determined at 2.35 A resolution. Shikimate 5-dehydrogenase (SDH) is responsible for NADP-dependent catalysis of the fourth step in shikimate biosynthesis, which is essential for aromatic amino acid metabolism in bacteria, microbial eukaryotes, and plants. The structure of MjSDH is a compact alpha/beta sandwich with two distinct domains, responsible for binding substrate and the NADP cofactor, respectively. A phylogenetically conserved deep cleft on the protein surface corresponds to the enzyme active site. The structure reveals a topologically new domain fold within the N-terminal segment of the polypeptide chain, which binds substrate and supports dimerization. Insights gained from homology modeling and sequence/structure comparisons suggest that the SDHs represent a unique class of dehydrogenases. The structure provides a framework for further investigation to discover and develop novel inhibitors targeting this essential enzyme.

Publication types

  • Comparative Study
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Alcohol Oxidoreductases / chemistry*
  • Alcohol Oxidoreductases / genetics
  • Alcohol Oxidoreductases / metabolism*
  • Amino Acid Sequence
  • Base Sequence
  • Binding Sites
  • Catalysis
  • Crystallography, X-Ray*
  • Dimerization
  • Evolution, Molecular*
  • Hydrogen Bonding
  • Methanococcus / enzymology
  • Methanococcus / genetics
  • Models, Molecular
  • Molecular Sequence Data
  • Molecular Structure
  • NADP / metabolism*
  • Phylogeny
  • Protein Binding
  • Protein Structure, Secondary
  • Protein Structure, Tertiary
  • Sequence Homology, Amino Acid
  • Shikimic Acid / metabolism
  • Spectrum Analysis, Raman
  • Substrate Specificity
  • Water / chemistry


  • Water
  • Shikimic Acid
  • NADP
  • Alcohol Oxidoreductases
  • Shikimate dehydrogenase

Associated data

  • PDB/1NVT