9qe3 | pdb_00009qe3

Structure of native leukocyte myeloperoxidase in complex with a truncated version of the Staphylococcal Peroxidase Inhibitor SPIN and selenocyanate at pH 5.5

spinqualitylabelsall models 9qe3, resolution 2.06Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 9qe3 is a 6 chain structure with sequence from Homo sapiens and Staphylococcus aureus. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 2.06Å Ligands: BMA, CA, CSO, FUC, HEM, MAN, NAG, SEK Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function Q2G0X2_STAA8 Publication Abstract from PubMed The heme enzyme myeloperoxidase is a key player in the innate immune defense. It uses hydrogen peroxide to produce bactericidal hypohalous acids from (pseudo)halides, foremost chloride, and thiocyanate in the neutrophil phagosome. However, the available structural data on the halide-binding site, the marked pH dependence of halide oxidation, and the atypical pK(a) of an active-site histidine 261 fail to fully account for the mechanism of halide oxidation by myeloperoxidase. In the present study, crystal structures of myeloperoxidase-halide complexes show that halides can integrate into the hydrogen-bonding network formed by conserved water molecules, without directly interacting with the deprotonated histidine at both acidic and neutral pH. Molecular dynamics simulations reveal that protonation of histidine 261 decreases active site rigidity and increases the flexibility of arginine 405. Together with the terminal residues of the myeloperoxidase heavy and light chains, arginine 405 contributes to halide transport into the active site. Kinetic analyses and simulations further demonstrate that sodium ions play a critical role as charge shields, enabling halides to traverse the negatively charged access channel, which represents a key bottleneck for halide binding. Thus, halide access to the active site is governed by a complex interplay of electrostatic interactions involving both solvent ions and charged amino acid residues. Halide binding by myeloperoxidase is regulated by access channel dynamics and charge interactions.,Leitgeb U, Crha R, Fegerl I, Furtmuller PG, Oostenbrink C, Pfanzagl V Int J Biol Macromol. 2025 Oct 4;330(Pt 2):148038. doi: , 10.1016/j.ijbiomac.2025.148038. PMID:41043752 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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