31ak: Difference between revisions
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==Structure of native human leukocyte myeloperoxidase== | |||
<StructureSection load='31ak' size='340' side='right'caption='[[31ak]], [[Resolution|resolution]] 2.18Å' scene=''> | |||
== Structural highlights == | |||
<table><tr><td colspan='2'>[[31ak]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=31AK OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=31AK FirstGlance]. <br> | |||
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">Electron Microscopy, [[Resolution|Resolution]] 2.18Å</td></tr> | |||
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=BMA:BETA-D-MANNOSE'>BMA</scene>, <scene name='pdbligand=CA:CALCIUM+ION'>CA</scene>, <scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=FUC:ALPHA-L-FUCOSE'>FUC</scene>, <scene name='pdbligand=HEM:PROTOPORPHYRIN+IX+CONTAINING+FE'>HEM</scene>, <scene name='pdbligand=MAN:ALPHA-D-MANNOSE'>MAN</scene>, <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene></td></tr> | |||
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=31ak FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=31ak OCA], [https://pdbe.org/31ak PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=31ak RCSB], [https://www.ebi.ac.uk/pdbsum/31ak PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=31ak ProSAT]</span></td></tr> | |||
</table> | |||
== Disease == | |||
[https://www.uniprot.org/uniprot/PERM_HUMAN PERM_HUMAN] Defects in MPO are the cause of myeloperoxidase deficiency (MPOD) [MIM:[https://omim.org/entry/254600 254600]. A disorder characterized by decreased myeloperoxidase activity in neutrophils and monocytes that results in disseminated candidiasis.<ref>PMID:8142659</ref> <ref>PMID:7904599</ref> <ref>PMID:8621627</ref> <ref>PMID:9637725</ref> <ref>PMID:9354683</ref> | |||
== Function == | |||
[https://www.uniprot.org/uniprot/PERM_HUMAN 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. | |||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
Myeloperoxidase (MPO) is a highly glycosylated heme oxidoreductase that, together with lactoperoxidase (LPO) and eosinophil peroxidase (EPO), contributes to host defence through the generation of (pseudo)hypohalous acids. Among the human heme peroxidases, mature MPO forms a unique covalently linked homodimer. Dimerization enhances stability and is essential for some biological functions, including chromatin disruption during neutrophil extracellular trap formation. Thus, we hypothesized that MPO dimerization must reflect a tightly regulated step in MPO biosynthesis and is driven by specific structural elements. Cross-species sequence alignment indicated that N-glycosylation motifs were evolutionarily more conserved in MPO than in monomeric EPO and LPO. We investigated the role of N-glycans in MPO dimerization using in vitro monomerized glycosylated (mMPO) and deglycosylated (mMPOdg) monomeric variants of native human MPO. Small-angle X-ray scattering, isothermal titration calorimetry and crystal structures showed that glycosylated MPO monomers had a weak but biologically relevant affinity in the millimolar range, which was lost upon deglycosylation. Furthermore, we present the first cryogenic transmission electron microscopy structure of human MPO with at least one core N-acetylglucosamine residue resolved at each N-glycosylation site. Structural analysis suggests that an extensive hydrogen bonding network of interface N-glycans at position 483 and residues of the other monomer drives MPO homodimerization. Dimerization enhances stability without affecting enzymatic activity. Together, we show that N-glycans are essential to MPO dimerization, provide important insights into the impact of interface N-glycans on biophysical and biochemical properties of MPO and discuss the implications for the biological roles of MPO in health and disease. | |||
Interface N-glycans drive myeloperoxidase dimerization in vitro.,Leitgeb U, Guo Y, Emde T, Ruocco V, Simak T, Zdenkovic E, Furtmuller PG, Borek D, Nauseef WM, Oostenbrink C, Pfanzagl V Int J Biol Macromol. 2026 Sep 14;383(Pt 1):154499. doi: , 10.1016/j.ijbiomac.2026.154499. PMID:42735772<ref>PMID:42735772</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
[[Category: | </div> | ||
<div class="pdbe-citations 31ak" style="background-color:#fffaf0;"></div> | |||
== References == | |||
<references/> | |||
__TOC__ | |||
</StructureSection> | |||
[[Category: Homo sapiens]] | |||
[[Category: Large Structures]] | |||
[[Category: Borek D]] | |||
[[Category: Emde T]] | |||
[[Category: Guo Y]] | |||
[[Category: Leitgeb U]] | |||
[[Category: Pfanzagl V]] | |||
