title: Crystal structure of GDP-mannose dehydrogenase: a key enzyme of alginate biosynthesis in P. aeruginosa.
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.
authors.affiliation: Department of Biochemistry, 117 Schweitzer Hall, University of Missouri-Columbia, Columbia, Missouri 65211, USA.
authors.forename: Christopher F
authors.initials: CF
authors.lastname: Snook
authors.forename: Peter A
authors.initials: PA
authors.lastname: Tipton
authors.forename: Lesa J
authors.initials: LJ
authors.lastname: Beamer
mesh_terms: D000464:Alginates / Q000378:metabolism; D001665:Binding Sites; D002237:Carbohydrate Dehydrogenases / Q000737:chemistry* / Q000378:metabolism; D018360:Crystallography, X-Ray; D019281:Dimerization; D006860:Hydrogen Bonding; D008024:Ligands; D008956:Models, Chemical; D008958:Models, Molecular; D009243:NAD / Q000737:chemistry / Q000378:metabolism; D009702:Nucleoside Diphosphate Sugars / Q000737:chemistry / Q000378:metabolism; D011550:Pseudomonas aeruginosa / Q000201:enzymology*; D014533:Uridine Diphosphate Glucose Dehydrogenase / Q000737:chemistry
chemical_list: D000464:Alginates; D008024:Ligands; D009702:Nucleoside Diphosphate Sugars; D009243:NAD; C037228:GDP mannuronic acid; D002237:Carbohydrate Dehydrogenases; C020562:GDPmannose dehydrogenase; D014533:Uridine Diphosphate Glucose Dehydrogenase