Aldoheptose Biosynthesis. Previously, a novobiocin-hypersensitive mutant of Escherichia coli K-12 carrying a cysE-pyrE linked mutation, designated rfaD, which specifically affects the synthesis of the aldoheptose, L-glycero-D-mannoheptose, has been isolated and genetically characterized. Recently, we have cloned a 2.5 kilobase fragment carrying the rfaD gene into several high copy plasmids. The rfaD gene has been expressed in several expression systems, and further characterization of the rfaD gene product is in progress. Hepatitis Non-A, NonB. Hepatitis non-A, nonB (HNANB) is a world-wide problem, and 90% of the transfusion-related hepatitis cases in the United States (and 80-90% in several other countries) are diagnosed as HNANB. Approximately 50% of all acute HNANB patients develop chronic HNANB (an estimate of 4 million persons). They remain as potential sources of infection. Recent publications suggest a correlation between certain hepatocellular carinomas and chronic HNANB infections. Based on biochemical, immunological, and morphological evidence, we suggested that the HNANB agent is a mammalian type C retrovirus. Recently, using an in vitro focus-induction assay developed for mammalian type C viruses, we observed that pelleted material from HNANB sera (transfusion-related) induced foci formation. This result is consistent with the presence of a mammalian type C virus in HNANB sera.

Project Start
Project End
Budget Start
Budget End
Support Year
8
Fiscal Year
1986
Total Cost
Indirect Cost
Name
U.S. National Inst Diabetes/Digst/Kidney
Department
Type
DUNS #
City
State
Country
United States
Zip Code
Morrison, James P; Read, Jay A; Coleman Jr, William G et al. (2005) Dismutase activity of ADP-L-glycero-D-manno-heptose 6-epimerase: evidence for a direct oxidation/reduction mechanism. Biochemistry 44:5907-15
Read, Jay A; Ahmed, Raef A; Morrison, James P et al. (2004) The mechanism of the reaction catalyzed by ADP-beta-L-glycero-D-manno-heptose 6-epimerase. J Am Chem Soc 126:8878-9
Nyan, Dougbeh C; Welch, Anthony R; Dubois, Andre et al. (2004) Development of a noninvasive method for detecting and monitoring the time course of Helicobacter pylori infection. Infect Immun 72:5358-64
Ni, Y; McPhie, P; Deacon, A et al. (2001) Evidence that NADP+ is the physiological cofactor of ADP-L-glycero-D-mannoheptose 6-epimerase. J Biol Chem 276:27329-34
Deacon, A M; Ni, Y S; Coleman Jr, W G et al. (2000) The crystal structure of ADP-L-glycero-D-mannoheptose 6-epimerase: catalysis with a twist. Structure 8:453-62
Ding, L; Zhang, Y; Deacon, A M et al. (1999) Crystallization and preliminary X-ray diffraction studies of the lipopolysaccharide core biosynthetic enzyme ADP-L-glycero-D-mannoheptose 6-epimerase from Escherichia coli K-12. Acta Crystallogr D Biol Crystallogr 55:685-8