Title | The first structure of UDP-glucose dehydrogenase reveals the catalytic residues necessary for the two-fold oxidation |
Publication Type | Journal Article |
Year of Publication | 2000 |
Authors | Campbell, RE, Mosimann, SC, van de Rijn, I, Tanner, ME, Strynadka, NCJ |
Journal | Biochemistry |
Volume | 39 |
Pagination | 7012-7023 |
Date Published | Jun |
Type of Article | Article |
ISBN Number | 0006-2960 |
Keywords | alanine, ALIGNMENT, CRYSTAL-STRUCTURE, ESCHERICHIA-COLI, GROUP-A STREPTOCOCCI, INSIGHTS, MECHANISM, MOLECULAR CHARACTERIZATION, REDUCTASE, SUBSTRATE-BINDING |
Abstract | Bacterial UDP-glucose dehydrogenase (UDPGlcDH) is essential for formation of the antiphagocytic capsule that protects many virulent bacteria such as Streptococcus pyrogenes and Streptococcus pneumoniae type 3 from the host’s immune system. We have determined the X-ray structures of both native and Cys260Ser UDPGlcDH from S. pyogenes (74% similarity to S. pneumoniae) in ternary complexes with UDP-xylose/NAD(+) and UDP-glucuronic acid/NAD(H), respectively. The 402 residue homodimeric UDPGlcDH is composed of an N-terminal NAD(+) dinucleotide binding domain and a C-terminal UDP-sugar binding domain connected by a long (48 Angstrom) central alpha-helix. The first 290 residues of UDPGlcDH share structural homology with 6-phosphogluconate dehydrogenase, including conservation of an active site lysine and asparagine that are implicated in the enzyme mechanism. Also proposed to participate in the catalytic mechanism are a threonine and a glutamate that hydrogen bond to a conserved active site water molecule suitably positioned for general acid/base catalysis. |
URL | <Go to ISI>://000087631000031 |
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