5LJI

Streptococcus pneumonia TIGR4 flavodoxin: structural and biophysical characterization of a novel drug target

Summary for 5LJI

• Entry DOI: 10.2210/pdb5lji/pdb
• Descriptor: Flavodoxin, FLAVIN MONONUCLEOTIDE, CALCIUM ION, ... (4 entities in total)
• Functional Keywords: flavodoxin, protein stability, fmn binding, drug target, streptococcus pneumoniae, oxidoreductase
• Biological source: Streptococcus pneumoniae
• Total number of polymer chains: 2
• Total formula weight: 33779.77

Authors

Rodriguez-Cardenas, A.,Rojas, A.L.,Velazquez-Campoy, A.,Hurtado-Guerrero, R.,Sancho, J. (deposition date: 2016-07-18, release date: 2016-08-31, Last modification date: 2024-10-09)

Primary citation

Rodriguez-Cardenas, A.,Rojas, A.L.,Conde-Gimenez, M.,Velazquez-Campoy, A.,Hurtado-Guerrero, R.,Sancho, J.
Streptococcus pneumoniae TIGR4 Flavodoxin: Structural and Biophysical Characterization of a Novel Drug Target.
Plos One, 11:e0161020-e0161020, 2016

PubMed Abstract: Streptococcus pneumoniae (Sp) strain TIGR4 is a virulent, encapsulated serotype that causes bacteremia, otitis media, meningitis and pneumonia. Increased bacterial resistance and limited efficacy of the available vaccine to some serotypes complicate the treatment of diseases associated to this microorganism. Flavodoxins are bacterial proteins involved in several important metabolic pathways. The Sp flavodoxin (Spfld) gene was recently reported to be essential for the establishment of meningitis in a rat model, which makes SpFld a potential drug target. To facilitate future pharmacological studies, we have cloned and expressed SpFld in E. coli and we have performed an extensive structural and biochemical characterization of both the apo form and its active complex with the FMN cofactor. SpFld is a short-chain flavodoxin containing 146 residues. Unlike the well-characterized long-chain apoflavodoxins, the Sp apoprotein displays a simple two-state thermal unfolding equilibrium and binds FMN with moderate affinity. The X-ray structures of the apo and holo forms of SpFld differ at the FMN binding site, where substantial rearrangement of residues at the 91-100 loop occurs to permit cofactor binding. This work will set up the basis for future studies aiming at discovering new potential drugs to treat S. pneumoniae diseases through the inhibition of SpFld.

PubMed: 27649488
DOI: 10.1371/journal.pone.0161020

Experimental method

X-RAY DIFFRACTION (2.07 Å)