5ZA4

Crystal structure of Sialic acid Binding protein from Haemophilus ducreyi

Summary for 5ZA4

• Entry DOI: 10.2210/pdb5za4/pdb
• Descriptor: Putative ABC transporter periplasmic binding protein (2 entities in total)
• Functional Keywords: three domain proteins, sialic acid neu5gc, molecular mimicry, adhesion, cell signaling, nutrition, sugar binding protein
• Biological source: Haemophilus ducreyi
• Total number of polymer chains: 1
• Total formula weight: 54390.75

Authors

Setty, T.G.,Subramanian, R. (deposition date: 2018-02-06, release date: 2018-10-24, Last modification date: 2023-11-22)

Primary citation

Gangi Setty, T.,Mowers, J.C.,Hobbs, A.G.,Maiya, S.P.,Syed, S.,Munson Jr., R.S.,Apicella, M.A.,Subramanian, R.
Molecular characterization of the interaction of sialic acid with the periplasmic binding protein fromHaemophilus ducreyi.
J. Biol. Chem., 293:20073-20084, 2018

PubMed Abstract: 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 , , , and SiaPs bind the sialic acid -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 The structure of -SatA in the native form and sialic acid-bound forms (with Neu5Ac and -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.

PubMed: 30315109
DOI: 10.1074/jbc.RA118.005151

Experimental method

X-RAY DIFFRACTION (2.193 Å)