A dimer between monomers and hexamers-Oligomeric variations in glucosamine-6-phosphate deaminase family

PLoS One. 2023 Jan 4;18(1):e0271654. doi: 10.1371/journal.pone.0271654. eCollection 2023.


In bacteria that live in hosts whose terminal sugar is a sialic acid, Glucosamine-6-phosphate deaminase (NagB) catalyzes the last step in converting sialic acid into Fructose-6-phosphate. These bacteria then use the Fructose-6-phosphate as an energy source. The enzyme NagB exists as a hexamer in Gram-negative bacteria and is allosterically regulated. In Gram-positive bacteria, it exists as a monomer and lacks allosteric regulation. Our identification of a dimeric Gram-negative bacterial NagB motivated us to characterize the structural basis of two closely related oligomeric forms. We report here the crystal structures of NagB from two Gram-negative pathogens, Haemophilus influenzae (Hi) and Pasturella multocida (Pm). The Hi-NagB is active as a hexamer, while Pm-NagB is active as a dimer. Both Hi-NagB and Pm-NagB contain the C-terminal helix implicated as essential for hexamer formation. The hexamer is described as a dimer of trimers. In the Pm-NagB dimer, the dimeric interface is conserved. The conservation of the dimer interface suggests that the three possible oligomeric forms of NagB are a monomer, a dimer, and a trimer of dimers. Computational modeling and MD simulations indicate that the residues at the trimeric interface have less stabilizing energy of oligomer formation than those in the dimer interface. We propose that Pm-NagB is the evolutionary link between the monomer and the hexamer forms.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aldose-Ketose Isomerases*
  • Bacterial Proteins*
  • Haemophilus influenzae* / enzymology
  • N-Acetylneuraminic Acid
  • Pasteurella multocida* / enzymology
  • Polymers


  • Aldose-Ketose Isomerases
  • glucosamine-6-phosphate isomerase
  • N-Acetylneuraminic Acid
  • Polymers
  • Bacterial Proteins

Grants and funding

This research was supported by the DBT/Wellcome Trust India Alliance Early Career Fellowship, Grant/Award Number: 500210-Z-11-Z to SS; RS thanks support from DBT‐B‐life grant, Grant/Award Number: BT/PR5081/INF/156/2012, DBT‐Indo Swedish Grant, Grant/Award Number: BT/IN/SWEDEN/06/SR/2017‐18, ESRF Access Program of RCB, Grant/Award Number: BT/INF/22/SP22660/2017, National Centre for Biological Sciences X‐ray facility grant, and Grant/Award Number: BT/PR12422/MED/31/287/214. RS acknowledges funding and support provided by the JC Bose Fellowship (SB/S2/JC-071/2015) from the Science and Engineering Research Board, India, and the Bioinformatics Center Grant funded by the Department of Biotechnology, India (BT/PR40187/BTIS/137/9/2021). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.