8uub

Structure of hypothiocyanous acid reductase (Har) from Streptococcus pneumoniae

spinqualitylabelsall models 8uub, resolution 1.50Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 8uub is a 1 chain structure with sequence from Streptococcus pneumoniae D39. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 1.5Å Ligands: FAD, MLI Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function A0A0H2ZMK9_STRP2 Publication Abstract from PubMed The major human pathogen Streptococcus pneumoniae encounters the immune-derived oxidant hypothiocyanous acid (HOSCN) at sites of colonization and infection. We recently identified the pneumococcal hypothiocyanous acid reductase (Har), a member of the flavoprotein disulfide reductase enzyme family, and showed that it contributes to the HOSCN tolerance of S. pneumoniae in vitro. Here, we demonstrate in mouse models of pneumococcal infection that Har is critical for colonization and invasion. In a colonization model, bacterial load was attenuated dramatically in the nasopharynx when har was deleted in S. pneumoniae. The Deltahar strain was also less virulent compared to wild type in an invasion model as reflected by a significant reduction in bacteria in the lungs and no dissemination to the blood and brain. Kinetic measurements with recombinant Har demonstrated that this enzyme reduced HOSCN with near diffusion-limited catalytic efficiency, using either NADH (k(cat)/K(M) = 1.2 x 10(8) M(-1)s(-1)) or NADPH (k(cat)/K(M) = 2.5 x 10(7) M(-1)s(-1)) as electron donors. We determined the X-ray crystal structure of Har in complex with the FAD cofactor to 1.50 A resolution, highlighting the active site architecture characteristic for this class of enzymes. Collectively, our results demonstrate that pneumococcal Har is a highly efficient HOSCN reductase, enabling survival against oxidative host immune defenses. In addition, we provide structural insights that may aid the design of Har inhibitors. Hypothiocyanous acid reductase is critical for host colonization and infection by Streptococcus pneumoniae.,Shearer HL, Currie MJ, Agnew HN, Trappetti C, Stull F, Pace PE, Paton JC, Dobson RCJ, Dickerhof N J Biol Chem. 2024 May;300(5):107282. doi: 10.1016/j.jbc.2024.107282. Epub 2024 , Apr 9. PMID:38604564 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

Proteopedia Page Contributors and Editors (what is this?)

OCA