5TYH
PglD from Campylobacter jejuni NCTC 11168 in complex with 5-(2-furanyl)-1H-pyrazole-3-carboxylic acid
Summary for 5TYH
| Entry DOI | 10.2210/pdb5tyh/pdb |
| Descriptor | UDP-N-acetylbacillosamine N-acetyltransferase, 3-(furan-2-yl)-1H-pyrazole-5-carboxylic acid (3 entities in total) |
| Functional Keywords | acetyltransferase bacterial n-glycan biosynthesis inhibitor fragment-based discovery, transferase, transferase-transferase inhibitor complex, transferase/transferase inhibitor |
| Biological source | Campylobacter jejuni subsp. jejuni serotype O:2 (strain ATCC 700819 / NCTC 11168) |
| Total number of polymer chains | 1 |
| Total formula weight | 21746.25 |
| Authors | Morrison, J.P.,Imperiali, B. (deposition date: 2016-11-20, release date: 2017-04-12, Last modification date: 2023-10-04) |
| Primary citation | De Schutter, J.W.,Morrison, J.P.,Morrison, M.J.,Ciulli, A.,Imperiali, B. Targeting Bacillosamine Biosynthesis in Bacterial Pathogens: Development of Inhibitors to a Bacterial Amino-Sugar Acetyltransferase from Campylobacter jejuni. J. Med. Chem., 60:2099-2118, 2017 Cited by PubMed Abstract: The glycoproteins of selected microbial pathogens often include highly modified carbohydrates such as 2,4-diacetamidobacillosamine (diNAcBac). These glycoconjugates are involved in host-cell interactions and may be associated with the virulence of medically significant Gram-negative bacteria. In light of genetic studies demonstrating the attenuated virulence of bacterial strains in which modified carbohydrate biosynthesis enzymes have been knocked out, we are developing small molecule inhibitors of selected enzymes as tools to evaluate whether such compounds modulate virulence. We performed fragment-based and high-throughput screens against an amino-sugar acetyltransferase enzyme, PglD, involved in biosynthesis of UDP-diNAcBac in Campylobacter jejuni. Herein we report optimization of the hits into potent small molecule inhibitors (IC < 300 nM). Biophysical characterization shows that the best inhibitors are competitive with acetyl coenzyme A and an X-ray cocrystal structure reveals that binding is biased toward occupation of the adenine subpocket of the AcCoA binding site by an aromatic ring. PubMed: 28182413DOI: 10.1021/acs.jmedchem.6b01869 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (2.1 Å) |
Structure validation
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