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Characterizing non-hydrolyzing Neisseria meningitidis serogroup A UDP-N-acetylglucosamine (UDP-GlcNAc) 2-epimerase using UDP-N-acetylmannosamine (UDP-ManNAc) and derivatives
- Source :
- Carbohydrate Research. 419:18-28
- Publication Year :
- 2016
- Publisher :
- Elsevier BV, 2016.
-
Abstract
- Neisseria meningitidis serogroup A non-hydrolyzing uridine 5'-diphosphate-N-acetylglucosamine (UDP-GlcNAc) 2-epimerase (NmSacA) catalyzes the interconversion between UDP-GlcNAc and uridine 5'-diphosphate-N-acetylmannosamine (UDP-ManNAc). It is a key enzyme involved in the biosynthesis of the capsular polysaccharide [-6ManNAcĪ±1-phosphate-]n of N. meningitidis serogroup A, one of the six serogroups (A, B, C, W-135, X, and Y) that account for most cases of N. meningitidis-caused bacterial septicemia and meningitis. N. meningitidis serogroup A is responsible for large epidemics in the developing world, especially in Africa. Here we report that UDP-ManNAc could be used as a substrate for C-terminal His6-tagged recombinant NmSacA (NmSacA-His6) in the absence of UDP-GlcNAc. NmSacA-His6 was activated by UDP-GlcNAc and inhibited by 2-acetamidoglucal and UDP. Substrate specificity study showed that NmSacA-His6 could tolerate several chemoenzymatically synthesized UDP-ManNAc derivatives as substrates although its activity was much lower than non-modified UDP-ManNAc. Homology modeling and molecular docking revealed likely structural determinants of NmSacA substrate specificity. This is the first detailed study of N. meningitidis serogroup A UDP-GlcNAc 2-epimerase.
- Subjects :
- 0301 basic medicine
UDP-GlcNAc 2-epimerase
Neisseria meningitidis
Biochemistry
Substrate Specificity
Analytical Chemistry
law.invention
chemistry.chemical_compound
law
N-Acetylmannosamine
Catalytic Domain
Epimerization
2.2 Factors relating to the physical environment
UDP-ManNAc
Cloning, Molecular
Enzyme Inhibitors
Aetiology
chemistry.chemical_classification
Uridine Diphosphate N-Acetylglucosamine
General Medicine
Molecular Docking Simulation
Recombinant DNA
Infection
Molecular Sequence Data
Polysaccharide
Article
Uridine Diphosphate
Microbiology
Medicinal and Biomolecular Chemistry
03 medical and health sciences
Rare Diseases
Biosynthesis
Amino Acid Sequence
Homology modeling
Organic Chemistry
Molecular
Substrate (chemistry)
Hexosamines
UDP-GlcNAc
Uridine
Enzyme Activation
carbohydrates (lipids)
030104 developmental biology
Enzyme
chemistry
Biochemistry and Cell Biology
Carbohydrate Epimerases
Cloning
Subjects
Details
- ISSN :
- 00086215
- Volume :
- 419
- Database :
- OpenAIRE
- Journal :
- Carbohydrate Research
- Accession number :
- edsair.doi.dedup.....03d28bb2d43e2b3ad62ca27eb637f889