Document Detail


Biosynthesis of a new UDP-sugar, UDP-2-acetamido-2-deoxyxylose, in the human pathogen Bacillus cereus subspecies cytotoxis NVH 391-98.
MedLine Citation:
PMID:  20529859     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
We have identified an operon and characterized the functions of two genes from the severe food-poisoning bacterium, Bacillus cereus subsp. cytotoxis NVH 391-98, that are involved in the synthesis of a unique UDP-sugar, UDP-2-acetamido-2-deoxyxylose (UDP-N-acetyl-xylosamine, UDP-XylNAc). UGlcNAcDH encodes a UDP-N-acetyl-glucosamine 6-dehydrogenase, converting UDP-N-acetylglucosamine (UDP-GlcNAc) to UDP-N-acetyl-glucosaminuronic acid (UDP-GlcNAcA). The second gene in the operon, UXNAcS, encodes a distinct decarboxylase not previously described in the literature, which catalyzes the formation of UDP-XylNAc from UDP-GlcNAcA in the presence of exogenous NAD(+). UXNAcS is specific and cannot utilize UDP-glucuronic acid and UDP-galacturonic acid as substrates. UXNAcS is active as a dimer with catalytic efficiency of 7 mM(-1) s(-1). The activity of UXNAcS is completely abolished by NADH but unaffected by UDP-xylose. A real-time NMR-based assay showed unambiguously the dual enzymatic conversions of UDP-GlcNAc to UDP-GlcNAcA and subsequently to UDP-XylNAc. From the analyses of all publicly available sequenced genomes, it appears that UXNAcS is restricted to pathogenic Bacillus species, including Bacillus anthracis and Bacillus thuringiensis. The identification of UXNAcS provides insight into the formation of UDP-XylNAc. Understanding the metabolic pathways involved in the utilization of this amino-sugar may allow the development of drugs to combat and eradicate the disease.
Authors:
Xiaogang Gu; John Glushka; Sung G Lee; Maor Bar-Peled
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, Non-P.H.S.     Date:  2010-06-07
Journal Detail:
Title:  The Journal of biological chemistry     Volume:  285     ISSN:  1083-351X     ISO Abbreviation:  J. Biol. Chem.     Publication Date:  2010 Aug 
Date Detail:
Created Date:  2010-08-02     Completed Date:  2010-09-20     Revised Date:  2011-08-25    
Medline Journal Info:
Nlm Unique ID:  2985121R     Medline TA:  J Biol Chem     Country:  United States    
Other Details:
Languages:  eng     Pagination:  24825-33     Citation Subset:  IM    
Affiliation:
Complex Carbohydrate Research Center, University of Georgia, Athens, Georgia 30602, USA.
Data Bank Information
Bank Name/Acc. No.:
GENBANK/GU784842;  GU784843
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MeSH Terms
Descriptor/Qualifier:
Bacillus cereus / metabolism*
Carbohydrate Sequence
Cloning, Molecular
Dimerization
Extracellular Matrix / metabolism
Gene Expression Regulation, Bacterial*
Gene Expression Regulation, Enzymologic*
Glycosaminoglycans / chemistry
Humans
Magnetic Resonance Spectroscopy
Models, Biological
Models, Chemical
Molecular Sequence Data
Recombinant Proteins / chemistry
Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization
Uridine Diphosphate Sugars / biosynthesis*,  chemistry
Uridine Diphosphate Xylose / chemistry*
Grant Support
ID/Acronym/Agency:
GM66340/GM/NIGMS NIH HHS
Chemical
Reg. No./Substance:
0/Glycosaminoglycans; 0/Recombinant Proteins; 0/UDP-2-acetamido-2-deoxyxylose; 0/Uridine Diphosphate Sugars; 3616-06-6/Uridine Diphosphate Xylose
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