UDP-glucose Dehydrogenase From Bovine Liver: Primary Structure and Relationship to Other Dehydrogenases

Protein Sci. 1994 Jul;3(7):1074-80. doi: 10.1002/pro.5560030710.

Abstract

The primary structure of bovine liver UDP-glucose dehydrogenase (UDPGDH), a hexameric, NAD(+)-linked enzyme, has been determined at the protein level. The 52-kDa subunits are composed of 468 amino acid residues, with a free N-terminus and a Ser/Asn microhetergeneity at one position. The sequence shares 29.6% positional identity with GDP-mannose dehydrogenase from Pseudomonas, confirming a similarity earlier noted between active site peptides. This degree of similarity is comparable to the 31.1% identity vs. the UDPGDH from type A Streptococcus. Database searching also revealed similarities to a hypothetical sequence from Salmonella typhimurium and to "UDP-N-acetyl-mannosaminuronic acid dehydrogenase" from Escherichia coli. Pairwise identities between bovine UDPGDH and each of these sequences were all in the range of approximately 26-34%. Multiple alignment of all 5 sequences indicates common ancestry for these 4-electron-transferring enzymes. There are 27 strictly conserved residues, including a cysteine residue at position 275, earlier identified by chemical modification as the expected catalytic residue of the second half-reaction (conversion of UDP-aldehydoglucose to UDP-glucuronic acid), and 2 lysine residues, at positions 219 and 338, one of which may be the expected catalytic residue for the first half-reaction (conversion of UDP-glucose to UDP-aldehydoglucose). A GXGXXG pattern characteristic of the coenzyme-binding fold is found at positions 11-16, close to the N-terminus as with "short-chain" alcohol dehydrogenases.(ABSTRACT TRUNCATED AT 250 WORDS)

Publication types

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

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Carbohydrate Dehydrogenases / chemistry
  • Cattle
  • Escherichia coli / enzymology
  • Liver / enzymology*
  • Molecular Sequence Data
  • Oxidoreductases / chemistry*
  • Pseudomonas / enzymology
  • Salmonella typhimurium / enzymology
  • Sequence Homology
  • Streptococcus pyogenes / enzymology
  • Uridine Diphosphate Glucose Dehydrogenase / chemistry*

Substances

  • Oxidoreductases
  • Carbohydrate Dehydrogenases
  • UDP-N-acetylmannosamine dehydrogenase
  • GDPmannose dehydrogenase
  • Uridine Diphosphate Glucose Dehydrogenase