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Molecular characterization of the interaction of sialic acid with the periplasmic binding protein from Haemophilus ducreyi

Journal Article · · Journal of Biological Chemistry
 [1];  [2];  [2];  [3];  [3];  [4];  [2];  [3]
  1. Inst. for Stem Cell Biology and Regenerative Medicine, Bangalore (India); Univ. of Trans-Disciplinary Health Sciences and Technology (TDU), Bangalore (India)
  2. Univ. of Iowa, Iowa City, IA (United States)
  3. Inst. for Stem Cell Biology and Regenerative Medicine, Bangalore (India)
  4. The Ohio State Univ., Columbus, OH (United States)
+ Show Author Affiliations

The primary role of bacterial periplasmic binding proteins is sequestration of essential metabolites present at a low concentration in the periplasm and making them available for active transporters that transfer these ligands into the bacterial cell. The periplasmic binding proteins (SiaPs) from the tripartite ATP-independent periplasmic (TRAP) transport system that transports mammalian host–derived sialic acids have been well studied from different pathogenic bacteria, including Haemophilus influenzae, Fusobacterium nucleatum, Pasteurella multocida, and Vibrio cholerae. SiaPs bind the sialic acid N-acetylneuraminic acid (Neu5Ac) with nanomolar affinity by forming electrostatic and hydrogen-bonding interactions. Here, we report the crystal structure of a periplasmic binding protein (SatA) of the ATP-binding cassette (ABC) transport system from the pathogenic bacterium Haemophilus ducreyi. The structure of Hd-SatA in the native form and sialic acid–bound forms (with Neu5Ac and N-glycolylneuraminic acid (Neu5Gc)), determined to 2.2, 1.5, and 2.5 Å resolutions, respectively, revealed a ligand-binding site that is very different from those of the SiaPs of the TRAP transport system. A structural comparison along with thermodynamic studies suggested that similar affinities are achieved in the two classes of proteins through distinct mechanisms, one enthalpically driven and the other entropically driven. In summary, our structural and thermodynamic characterization of Hd-SatA reveals that it binds sialic acids with nanomolar affinity and that this binding is an entropically driven process. This information is important for future structure-based drug design against this pathogen and related bacteria.

Research Organization:
Argonne National Laboratory (ANL), Argonne, IL (United States)
Sponsoring Organization:
USDOE
OSTI ID:
1545842
Journal Information:
Journal of Biological Chemistry, Journal Name: Journal of Biological Chemistry Journal Issue: 52 Vol. 293; ISSN 0021-9258
Publisher:
American Society for Biochemistry and Molecular BiologyCopyright Statement
Country of Publication:
United States
Language:
ENGLISH

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Cited By (2)

Elucidation of a sialic acid metabolism pathway in mucus-foraging Ruminococcus gnavus unravels mechanisms of bacterial adaptation to the gut journal October 2019
Determination of an Interaction Network between an Extracellular Bacterial Pathogen and the Human Host journal June 2019

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Related Subjects

37 INORGANIC, ORGANIC, PHYSICAL, AND ANALYTICAL CHEMISTRY
59 BASIC BIOLOGICAL SCIENCES
ABC transporter
Haemophilus ducreyi
crystal structure
energetics
enthalpy entropy
isothermal titration calorimetry (ITC)
nutrient sequestration
periplasmic binding protein
sialic acid
sugar transport
virulence