6JKU

Crystal structure of N-acetylglucosamine-6-phosphate deacetylase from Pasteurella Multocida

Summary for 6JKU

• Entry DOI: 10.2210/pdb6jku/pdb
• Descriptor: N-acetylglucosamine-6-phosphate deacetylase, ZINC ION, PHOSPHATE ION, ... (7 entities in total)
• Functional Keywords: deacetylase, sialic acid catabolism pathway, metal binding protein
• Biological source: Pasteurella multocida
• Total number of polymer chains: 4
• Total formula weight: 174914.85

Authors

Manjunath, L.,Bose, S.,Subramanian, R. (deposition date: 2019-03-01, release date: 2020-03-04, Last modification date: 2023-11-22)

Primary citation

Manjunath, L.,Coombes, D.,Davies, J.,Dhurandhar, M.,Tiwari, V.R.,Dobson, R.C.J.,Sowdhamini, R.,Ramaswamy, S.,Bose, S.
Quaternary variations in the structural assembly of N-acetylglucosamine-6-phosphate deacetylase from Pasteurella multocida.
Proteins, 2020

PubMed Abstract: N-acetylglucosamine 6-phosphate deacetylase (NagA) catalyzes the conversion of N-acetylglucosamine-6-phosphate to glucosamine-6-phosphate in amino sugar catabolism. This conversion is an essential step in the catabolism of sialic acid in several pathogenic bacteria, including Pasteurella multocida, and thus NagA is identified as a potential drug target. Here, we report the unique structural features of NagA from P. multocida (PmNagA) resolved to 1.95 Å. PmNagA displays an altered quaternary architecture with unique interface interactions compared to its close homolog, the Escherichia coli NagA (EcNagA). We confirmed that the altered quaternary structure is not a crystallographic artifact using single particle electron cryo-microscopy. Analysis of the determined crystal structure reveals a set of hot-spot residues involved in novel interactions at the dimer-dimer interface. PmNagA binds to one Zn ion in the active site and demonstrates kinetic parameters comparable to other bacterial homologs. Kinetic studies reveal that at high substrate concentrations (~10-fold the K ), the tetrameric PmNagA displays hysteresis similar to its distant neighbor, the dimeric Staphylococcus aureus NagA (SaNagA). Our findings provide key information on structural and functional properties of NagA in P. multocida that could be utilized to design novel antibacterials.

PubMed: 32865821
DOI: 10.1002/prot.25996

Experimental method

X-RAY DIFFRACTION (1.95 Å)