6bmt

Crystal Structure of a Recombinant form of Human Myeloperoxidase Bound to an Inhibitor from Staphylococcus delphini

spinqualitylabelsall models 6bmt, resolution 2.40Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 6bmt is a 2 chain structure with sequence from Atcc 49171 and Human. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Ligands: CA, CL, HEM, NAG Related: 5uzu Gene: MPO (HUMAN) Activity: Myeloperoxidase, with EC number 1.11.2.2 Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Disease [PERM_HUMAN] Defects in MPO are the cause of myeloperoxidase deficiency (MPOD) [MIM:254600]. A disorder characterized by decreased myeloperoxidase activity in neutrophils and monocytes that results in disseminated candidiasis. Function [PERM_HUMAN] Part of the host defense system of polymorphonuclear leukocytes. It is responsible for microbicidal activity against a wide range of organisms. In the stimulated PMN, MPO catalyzes the production of hypohalous acids, primarily hypochlorous acid in physiologic situations, and other toxic intermediates that greatly enhance PMN microbicidal activity. Publication Abstract from PubMed Staphylococcus aureus and related species are highly adapted to their hosts and have evolved numerous strategies to evade the immune system. S. aureus shows resistance to killing following uptake into the phagosome, which suggests that the bacterium evades intracellular killing mechanisms used by neutrophils. We recently discovered an S. aureus protein (SPIN for Staphylococcal Peroxidase INhibitor) that binds to and inhibits myeloperoxidase (MPO), a major player in the oxidative defense of neutrophils. To allow for comparative studies between multiple SPIN sequences, we identified a panel of homologs from species closely related to S. aureus. Characterization of these proteins revealed that SPIN molecules from S. agnetis, S. delphini, S. schleiferi, and S. intermedius all bind human MPO with nanomolar affinities, and that those from S. delphini, S. schleiferi, and S. intermedius inhibit human MPO in a dose-dependent manner. A 2.4A resolution co-crystal structure of SPIN-delphini bound to recombinant human MPO allowed us to identify conserved structural features of SPIN proteins, and to propose sequence-dependent physical explanations for why SPIN-aureus binds human MPO with higher affinity than SPIN-delphini. Together, these studies expand our understanding of MPO binding and inhibition by a recently identified component of the staphylococcal innate immune evasion arsenal. Identification and structural characterization of a novel myeloperoxidase inhibitor from Staphylococcus delphini.,Ploscariu NT, de Jong NWM, van Kessel KPM, van Strijp JAG, Geisbrecht BV Arch Biochem Biophys. 2018 Mar 7;645:1-11. doi: 10.1016/j.abb.2018.03.007. PMID:29524428 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Myeloperoxidase

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