7BVJ
UDP-N-acetylglucosamine 3-dehydrogenase GnnA from Acidithiobacillus ferrooxidans (P21)
Summary for 7BVJ
| Entry DOI | 10.2210/pdb7bvj/pdb |
| Descriptor | Oxidoreductase, NAD-binding, NICOTINAMIDE-ADENINE-DINUCLEOTIDE, (2R,3R)-2,3-bis(oxidanyl)butane-1,4-disulfonic acid, ... (4 entities in total) |
| Functional Keywords | gnna, oxidoreductase, udp-glcnac, lipopolysaccharide, udp-n-acetylglucosamine 3-dehydrogenase |
| Biological source | Acidithiobacillus ferrooxidans (strain ATCC 23270 / DSM 14882 / CIP 104768 / NCIMB 8455) |
| Total number of polymer chains | 4 |
| Total formula weight | 143557.53 |
| Authors | Wangkanont, K. (deposition date: 2020-04-10, release date: 2020-12-02, Last modification date: 2023-11-29) |
| Primary citation | Manissorn, J.,Sitthiyotha, T.,Montalban, J.R.E.,Chunsrivirot, S.,Thongnuek, P.,Wangkanont, K. Biochemical and Structural Investigation of GnnA in the Lipopolysaccharide Biosynthesis Pathway of Acidithiobacillus ferrooxidans . Acs Chem.Biol., 15:3235-3243, 2020 Cited by PubMed Abstract: Lipopolysaccharide (LPS) is a crucial component in the outer membrane of Gram-negative bacteria that contributes to both pathogenicity as well as immunity against pathogenic bacteria. Typical LPS contains GlcN disaccharide as the core of lipid A. However, some bacteria such as and contain GlcN3N in lipid A instead. This modification has been shown to dampen the host immune response and increase resistance to antimicrobial peptides. Therefore, investigation of the enzymes responsible for the biosynthesis of GlcN3N has promising applications in the development of vaccines, antibiotics, or usage of the enzymes in chemoenzymatic synthesis of modified LPS. Here, we describe biochemical and structural investigation of GnnA from (GnnA) that is responsible for oxidation of UDP-GlcNAc, which subsequently undergoes transamination to produce UDP-GlcNAc3N as a precursor for LPS biosynthesis. GnnA is specific for NAD and UDP-GlcNAc. The crystal structures of GnnA in combination with molecular dynamics simulation and mutational analysis suggest the substrate recognition mode and the catalytic mechanism. K91 or H164 is a potential catalytic base in the oxidation reaction. The results will not only provide insights into the biosynthesis of unusual LPS but will also lay the foundation for development of more immunogenic vaccines, novel antibiotics, or utilization of GnnA in the synthesis of UDP-sugars or modified LPS. PubMed: 33200610DOI: 10.1021/acschembio.0c00791 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (2.15 Å) |
Structure validation
Download full validation report
