Crystal structure of GDP-mannose dehydrogenase: a key enzyme of alginate biosynthesis in P. aeruginosa

Biochemistry. 2003 Apr 29;42(16):4658-68. doi: 10.1021/bi027328k.

Abstract

The enzyme GMD from Pseudomonas aeruginosa catalyzes the committed step in the synthesis of the exopolysaccharide alginate. Alginate is a major component of P. aeruginosa biofilms that protect the bacteria from the host immune response and antibiotic therapy. The 1.55 A crystal structure of GMD in ternary complex with its cofactor NAD(H) and product GDP-mannuronic acid reveals that the enzyme forms a domain-swapped dimer with two polypeptide chains contributing to each active site. The extensive dimer interface provides multiple opportunities for intersubunit communication. Comparison of the GMD structure with that of UDP-glucose dehydrogenase reveals the structural basis of sugar binding specificity that distinguishes these two related enzyme families. The high-resolution structure of GMD provides detailed information on the active site of the enzyme and a template for structure-based inhibitor design.

Publication types

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

MeSH terms

  • Alginates / metabolism
  • Binding Sites
  • Carbohydrate Dehydrogenases / chemistry*
  • Carbohydrate Dehydrogenases / metabolism
  • Crystallography, X-Ray
  • Dimerization
  • Hydrogen Bonding
  • Ligands
  • Models, Chemical
  • Models, Molecular*
  • NAD / chemistry
  • NAD / metabolism
  • Nucleoside Diphosphate Sugars / chemistry
  • Nucleoside Diphosphate Sugars / metabolism
  • Pseudomonas aeruginosa / enzymology*
  • Uridine Diphosphate Glucose Dehydrogenase / chemistry

Substances

  • Alginates
  • Ligands
  • Nucleoside Diphosphate Sugars
  • NAD
  • GDP mannuronic acid
  • Carbohydrate Dehydrogenases
  • GDPmannose dehydrogenase
  • Uridine Diphosphate Glucose Dehydrogenase

Associated data

  • PDB/1MF2
  • PDB/1MUU
  • PDB/1MV8