5M6D

Streptococcus pneumoniae Glyceraldehyde-3-Phosphate Dehydrogenase (SpGAPDH) crystal structure

Summary for 5M6D

• Entry DOI: 10.2210/pdb5m6d/pdb
• Descriptor: Glyceraldehyde-3-phosphate dehydrogenase, CHLORIDE ION, CALCIUM ION, ... (6 entities in total)
• Functional Keywords: gapdh, host/pathogen, plasminogen binding, oxidoreductase
• Biological source: Streptococcus pneumoniae
• Total number of polymer chains: 2
• Total formula weight: 77388.00

Authors

Gaboriaud, C.,Moreau, C.P.,Di Guilmi, A.M. (deposition date: 2016-10-25, release date: 2017-01-11, Last modification date: 2024-01-17)

Primary citation

Moreau, C.,Terrasse, R.,Thielens, N.M.,Vernet, T.,Gaboriaud, C.,Di Guilmi, A.M.
Deciphering Key Residues Involved in the Virulence-promoting Interactions between Streptococcus pneumoniae and Human Plasminogen.
J. Biol. Chem., 292:2217-2225, 2017

PubMed Abstract: Bacterial pathogens recruit circulating proteins to their own surfaces, co-opting the host protein functions as a mechanism of virulence. Particular attention has focused on the binding of plasminogen (Plg) to bacterial surfaces, as it has been shown that this interaction contributes to bacterial adhesion to host cells, invasion of host tissues, and evasion of the immune system. Several bacterial proteins are known to serve as receptors for Plg including glyceraldehyde-3-phosphate dehydrogenase (GAPDH), a cytoplasmic enzyme that appears on the cell surface in this moonlighting role. Although Plg typically binds to these receptors via several lysine-binding domains, the specific interactions that occur have not been documented in all cases. However, identification of the relevant residues could help define strategies for mitigating the virulence of important human pathogens, such as (Sp). To shed light on this question, we have described a combination of peptide-spot array screening, competition and SPR assays, high-resolution crystallography, and mutational analyses to characterize the interaction between SpGAPDH and Plg. We identified three SpGAPDH lysine residues that were instrumental in defining the kinetic and thermodynamic parameters of the interaction. Altogether, the integration of the data presented in this work allows us to propose a structural model for the molecular interaction of the SpGAPDH-Plg complex.

PubMed: 28011643
DOI: 10.1074/jbc.M116.764209

Experimental method

X-RAY DIFFRACTION (2 Å)