Bacillus subtilis PgcA moonlights as a phosphoglucosamine mutase in support of peptidoglycan synthesis
| Autor: | Katherine A. Black, Kyu Y. Rhee, John D. Helmann, Vaidehi Patel |
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| Rok vydání: | 2019 |
| Předmět: |
Cancer Research
Polymers Phosphoglucosamine mutase activity Bacillus Bacillus subtilis QH426-470 Pathology and Laboratory Medicine Biochemistry chemistry.chemical_compound Database and Informatics Methods 0302 clinical medicine Glucosamine Antibiotics Medicine and Health Sciences Materials Genetics (clinical) chemistry.chemical_classification 0303 health sciences Phosphoglucosamine mutase Organic Compounds Antimicrobials Monosaccharides Drugs Bacterial Pathogens Enzymes Nucleic acids Bacillus Subtilis Chemistry Experimental Organism Systems Macromolecules Medical Microbiology Gain of Function Mutation Physical Sciences Prokaryotic Models Phosphoglucomutase Pathogens Sequence Analysis Research Article Bioinformatics Materials Science Carbohydrates Peptidoglycan Biology DNA replication Research and Analysis Methods Biosynthesis Microbiology 03 medical and health sciences Bacterial Proteins Microbial Control Genetics Molecular Biology Microbial Pathogens Ecology Evolution Behavior and Systematics 030304 developmental biology Pharmacology Bacteria Organic Chemistry Organisms Chemical Compounds Biology and Life Sciences Proteins DNA Peptidoglycans biology.organism_classification Polymer Chemistry carbohydrates (lipids) Enzyme Glucose chemistry Animal Studies Enzymology Synthetic Lethal Mutations Sequence Alignment 030217 neurology & neurosurgery |
| Zdroj: | PLoS Genetics PLoS Genetics, Vol 15, Iss 10, p e1008434 (2019) |
| ISSN: | 1553-7404 |
| Popis: | Phosphohexomutase superfamily enzymes catalyze the reversible intramolecular transfer of a phosphoryl moiety on hexose sugars. Bacillus subtilis phosphoglucomutase PgcA catalyzes the reversible interconversion of glucose 6-phosphate (Glc-6-P) and glucose 1-phosphate (Glc-1-P), a precursor of UDP-glucose (UDP-Glc). B. subtilis phosphoglucosamine mutase (GlmM) is a member of the same enzyme superfamily that converts glucosamine 6-phosphate (GlcN-6-P) to glucosamine 1-phosphate (GlcN-1-P), a precursor of the amino sugar moiety of peptidoglycan. Here, we present evidence that B. subtilis PgcA possesses activity as a phosphoglucosamine mutase that contributes to peptidoglycan biosynthesis. This activity was made genetically apparent by the synthetic lethality of pgcA with glmR, a positive regulator of amino sugar biosynthesis, which can be specifically suppressed by overproduction of GlmM. A gain-of-function mutation in a substrate binding loop (PgcA G47S) increases this secondary activity and suppresses a glmR mutant. Our results demonstrate that bacterial phosphoglucomutases may possess secondary phosphoglucosamine mutase activity, and that this dual activity may provide some level of functional redundancy for the essential peptidoglycan biosynthesis pathway. Author summary Enzyme promiscuity results when an enzyme interacts with multiple, often structurally related, substrates. Phosphohexomutase family enzymes function in diverse pathways by catalyzing the isomerization of 6-phosphosugars and 1-phosphosugars. In Bacillus subtilis, the phosphoglucomutase (PGM) PgcA functions with glucose 6-phosphate (Glc-6-P) as substrate in support of UDP-glucose biosynthesis for glucolipid and teichoic acid synthesis. A separate phosphoglucosamine mutase (PNGM) designated GlmM functions with glucosamine 6-phosphate (GlcN-6-P) as substrate in the synthesis of aminosugars needed for peptidoglycan assembly. Here, we show that PgcA has a significant secondary activity as a PNGM and thereby contributes to PG synthesis. These results support a model in which a subset of bacterial PGM enzymes function as bifunctional PGM/PNGM enzymes, thereby providing functional redundancy for the essential process of cell wall synthesis. |
| Databáze: | OpenAIRE |
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