5mfa: Difference between revisions
New page: '''Unreleased structure''' The entry 5mfa is ON HOLD Authors: Grishkovskaya, I., Furtmueller, P.G., Obinger, C., Djinovic-Carugo, K. Description: Crystal structure of human promyeloper... |
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==Crystal structure of human promyeloperoxidase (proMPO)== | |||
<StructureSection load='5mfa' size='340' side='right'caption='[[5mfa]], [[Resolution|resolution]] 1.20Å' scene=''> | |||
== Structural highlights == | |||
<table><tr><td colspan='2'>[[5mfa]] is a 1 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=5MFA OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5MFA FirstGlance]. <br> | |||
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.2Å</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=CSO:S-HYDROXYCYSTEINE'>CSO</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>, <scene name='pdbligand=PEG:DI(HYDROXYETHYL)ETHER'>PEG</scene>, <scene name='pdbligand=TRS:2-AMINO-2-HYDROXYMETHYL-PROPANE-1,3-DIOL'>TRS</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=5mfa FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5mfa OCA], [https://pdbe.org/5mfa PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5mfa RCSB], [https://www.ebi.ac.uk/pdbsum/5mfa PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5mfa 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 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 remain, such as the structure-function relationships of monomeric unprocessed proMPO versus the mature dimeric MPO and the functional role of the propeptide. Here we present the first and high resolution (at 1.25 A) crystal structure of proMPO and its solution structure obtained by small angle X-ray scattering. Promyeloperoxidase hosts five occupied glycosylation sites and six intrachain cystine bridges with C158 of the very flexible N-terminal propeptide being covalently linked to C319 thereby hindering homodimerization. Furthermore, the structure revealed (i) the binding site of proMPO processing proconvertase, (ii) the structural motif for subsequent cleavage to the heavy and light chains of mature MPO protomers and (iii) three covalent bonds between heme and the protein. Studies on the mutants C158A, C319A and C158A/C319A demonstrate significant differences from the wild-type protein, including diminished enzymatic activity and prevention from export to the Golgi due to prolonged association with the chaperone calnexin. These structural and functional data provide novel insights into MPO biosynthesis and processing. | |||
Structure of human promyeloperoxidase (proMPO) and the role of the propeptide for processing and maturation.,Grishkovskaya I, Paumann-Page M, Tscheliessnig R, Stampler J, Hofbauer S, Soudi M, Sevcnikar B, Oostenbrink C, Furtmuller PG, Djinovic-Carugo K, Nauseef WM, Obinger C J Biol Chem. 2017 Mar 27. pii: jbc.M117.775031. doi: 10.1074/jbc.M117.775031. PMID:28348079<ref>PMID:28348079</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
[[Category: | </div> | ||
[[Category: Djinovic-Carugo | <div class="pdbe-citations 5mfa" style="background-color:#fffaf0;"></div> | ||
[[Category: | |||
[[Category: | ==See Also== | ||
[[Category: | *[[Myeloperoxidase|Myeloperoxidase]] | ||
== References == | |||
<references/> | |||
__TOC__ | |||
</StructureSection> | |||
[[Category: Homo sapiens]] | |||
[[Category: Large Structures]] | |||
[[Category: Djinovic-Carugo K]] | |||
[[Category: Furtmueller PG]] | |||
[[Category: Grishkovskaya I]] | |||
[[Category: Obinger C]] | |||