Enzymology
Structure of human promyeloperoxidase (proMPO) and the role of the propeptide in processing and maturation
Myeloperoxidase (MPO) is synthesized by neutrophil and monocyte precursor cells and contributes to host defense by mediating microbial killing. Although several steps in MPO biosynthesis and processing have been elucidated, many questions remained, such as the structure-function relationship of monomeric unprocessed proMPO versus the mature dimeric MPO and the functional role of the propeptide. Here we have presented the first and high resolution (at 1.25 Å) crystal structure of proMPO and its solution structure obtained by small-angle X-ray scattering.Pre-steady-state Kinetics Reveal the Substrate Specificity and Mechanism of Halide Oxidation of Truncated Human Peroxidasin 1
Human peroxidasin 1 is a homotrimeric multidomain peroxidase that is secreted to the extracellular matrix. The heme enzyme was shown to release hypobromous acid that mediates the formation of specific covalent sulfilimine bonds to reinforce collagen IV in basement membranes. Maturation by proteolytic cleavage is known to activate the enzyme. Here, we present the first multimixing stopped-flow study on a fully functional truncated variant of human peroxidasin 1 comprising four immunoglobulin-like domains and the catalytically active peroxidase domain.Multidomain Human Peroxidasin 1 Is a Highly Glycosylated and Stable Homotrimeric High Spin Ferric Peroxidase
Background: Human peroxidasin 1 (hsPxd01) mediates the formation of sulfilimine cross-links within the collagen IV scaffold of basement membranes.Results: Overexpressed hsPxd01 contains covalently linked heme catalytically active for production of hypobromous acid.Conclusion: hsPxd01 has peroxidase-like active site structure but restricted substrate accessibility.Significance: Architecture of hsPxd01 facilitates product release and its interactions with the physiological substrate collagen IV.
