7qzr - Revision history

OCA at 11:08, 15 November 2023

OCA — Wed, 15 Nov 2023 11:08:33 GMT

←Older revision		Revision as of 11:08, 15 November 2023
Line 4:		Line 4:
	== Structural highlights ==		== Structural highlights ==
	<table><tr><td colspan='2'>[[7qzr]] is a 6 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] and [https://en.wikipedia.org/wiki/Staphylococcus_aureus Staphylococcus aureus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7QZR OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7QZR FirstGlance]. <br>		<table><tr><td colspan='2'>[[7qzr]] is a 6 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] and [https://en.wikipedia.org/wiki/Staphylococcus_aureus Staphylococcus aureus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7QZR OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7QZR FirstGlance]. <br>
-	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=2CO:S-HYDROPEROXYCYSTEINE'>2CO</scene>, <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=EDO:1,2-ETHANEDIOL'>EDO</scene>, <scene name='pdbligand=FUC:ALPHA-L-FUCOSE'>FUC</scene>, <scene name='pdbligand=HEC:HEME+C'>HEC</scene>, <scene name='pdbligand=I7F:O-hydroxy-L-serine'>I7F</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=PO4:PHOSPHATE+ION'>PO4</scene></td></tr>	+	</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models\|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[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=2CO:S-HYDROPEROXYCYSTEINE'>2CO</scene>, <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=EDO:1,2-ETHANEDIOL'>EDO</scene>, <scene name='pdbligand=FUC:ALPHA-L-FUCOSE'>FUC</scene>, <scene name='pdbligand=HEC:HEME+C'>HEC</scene>, <scene name='pdbligand=I7F:O-hydroxy-L-serine'>I7F</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=PO4:PHOSPHATE+ION'>PO4</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=7qzr FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7qzr OCA], [https://pdbe.org/7qzr PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7qzr RCSB], [https://www.ebi.ac.uk/pdbsum/7qzr PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7qzr ProSAT]</span></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=7qzr FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7qzr OCA], [https://pdbe.org/7qzr PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7qzr RCSB], [https://www.ebi.ac.uk/pdbsum/7qzr PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7qzr ProSAT]</span></td></tr>
	</table>		</table>
Line 20:		Line 21:
	</div>		</div>
	<div class="pdbe-citations 7qzr" style="background-color:#fffaf0;"></div>		<div class="pdbe-citations 7qzr" style="background-color:#fffaf0;"></div>
		+
		+	==See Also==
		+	*[[Myeloperoxidase\|Myeloperoxidase]]
	== References ==		== References ==
	<references/>		<references/>

OCA at 06:01, 26 October 2022

OCA — Wed, 26 Oct 2022 06:01:51 GMT

←Older revision		Revision as of 06:01, 26 October 2022
Line 1:		Line 1:
-	'''Unreleased structure'''

-	~~The entry~~ 7qzr is ~~ON HOLD until Paper~~ Publication	+	==Structure of native leukocyte myeloperoxidase in complex with the Staphyloccal Peroxidase Inhibitor SPIN from Staphylococcus aureus==
		+	<StructureSection load='7qzr' size='340' side='right'caption='[[7qzr]], [[Resolution\|resolution]] 2.18Å' scene=''>
		+	== Structural highlights ==
		+	<table><tr><td colspan='2'>[[7qzr]] is a 6 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] and [https://en.wikipedia.org/wiki/Staphylococcus_aureus Staphylococcus aureus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7QZR OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7QZR FirstGlance]. <br>
		+	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=2CO:S-HYDROPEROXYCYSTEINE'>2CO</scene>, <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=EDO:1,2-ETHANEDIOL'>EDO</scene>, <scene name='pdbligand=FUC:ALPHA-L-FUCOSE'>FUC</scene>, <scene name='pdbligand=HEC:HEME+C'>HEC</scene>, <scene name='pdbligand=I7F:O-hydroxy-L-serine'>I7F</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=PO4:PHOSPHATE+ION'>PO4</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=7qzr FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7qzr OCA], [https://pdbe.org/7qzr PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7qzr RCSB], [https://www.ebi.ac.uk/pdbsum/7qzr PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7qzr 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 ==
		+	The heme enzyme myeloperoxidase (MPO) is one of the key players in the neutrophil-mediated killing of invading pathogens as part of the innate immune system. MPO generates antimicrobial oxidants which indiscriminately and effectively kill phagocytosed pathogens. Staphylococcus aureus however is able to escape this fate, in part by secreting a small protein called SPIN (Staphylococcal Peroxidase Inhibitor), which specifically targets and inhibits MPO in a structurally complex manner. Here we present the first crystal structures of the complex of SPIN-aureus and a truncated version (SPIN-truncated) with mature dimeric leukocyte MPO. We unravel the contributions of the two domains to the kinetics and thermodynamics of SPIN-aureus binding to MPO by using a broad array of complementary biochemical and biophysical methods. The C-terminal "recognition" domain is shown to mediate specific binding to MPO, while interaction of the N-terminal "inhibitory" domain is guided mainly by hydrophobic effects and thus is less sequence-dependent. We found that inhibition of MPO is achieved by reducing substrate migration, but SPIN-aureus cannot completely block MPO activity. Its' effectiveness is inversely related to substrate size, with no discernible dependence on other factors. Thus, SPIN-aureus is an extremely high-affinity inhibitor and highly efficient for substrates larger than halogens. As aberrant MPO activity is implicated in a number of chronic inflammatory diseases, SPIN-aureus is the first promising protein inhibitor for specific inhibition of human MPO.

-	~~Authors: Pfanzagl, V~~., Brito, J.A.	+	The staphylococcal inhibitory protein SPIN binds to human myeloperoxidase with picomolar affinity but only dampens halide oxidation.,Leitgeb U, Furtmuller PG, Hofbauer S, Brito JA, Obinger C, Pfanzagl V J Biol Chem. 2022 Sep 20:102514. doi: 10.1016/j.jbc.2022.102514. PMID:36150500<ref>PMID:36150500</ref>

-	~~Description: Structure~~ of ~~native leukocyte myeloperoxidase in complex with~~ the ~~Staphyloccal Peroxidase Inhibitor SPIN from Staphylococcus aureus~~	+	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
-	[[Category: ~~Unreleased~~ Structures]]	+	</div>
-	[[Category: ~~Pfanzagl, V~~]]	+	<div class="pdbe-citations 7qzr" style="background-color:#fffaf0;"></div>
-	[[Category: Brito~~, J.A~~]]	+	== References ==
		+	<references/>
		+	__TOC__
		+	</StructureSection>
		+	[[Category: Homo sapiens]]
		+	[[Category: Large Structures]]
		+	[[Category: Staphylococcus aureus]]
		+	[[Category: Brito JA]]
		+	[[Category: Pfanzagl V]]

OCA at 06:38, 25 May 2022

OCA — Wed, 25 May 2022 06:38:25 GMT

←Older revision		Revision as of 06:38, 25 May 2022
Line 1:		Line 1:
	'''Unreleased structure'''		'''Unreleased structure'''

-	The entry 7qzr is ON HOLD	+	The entry 7qzr is ON HOLD until Paper Publication

	Authors: Pfanzagl, V., Brito, J.A.		Authors: Pfanzagl, V., Brito, J.A.

OCA: Protected "7qzr" [edit=sysop:move=sysop]

OCA — Wed, 09 Feb 2022 06:09:56 GMT

Protected "7qzr" [edit=sysop:move=sysop]

←Older revision

Revision as of 06:09, 9 February 2022

OCA: New page: '''Unreleased structure''' The entry 7qzr is ON HOLD Authors: Pfanzagl, V., Brito, J.A. Description: Structure of native leukocyte myeloperoxidase in complex with the Staphyloccal Pero...

OCA — Wed, 09 Feb 2022 06:09:55 GMT

New page: '''Unreleased structure''' The entry 7qzr is ON HOLD Authors: Pfanzagl, V., Brito, J.A. Description: Structure of native leukocyte myeloperoxidase in complex with the Staphyloccal Pero...

New page

'''Unreleased structure'''

The entry 7qzr is ON HOLD

Authors: Pfanzagl, V., Brito, J.A.

Description: Structure of native leukocyte myeloperoxidase in complex with the Staphyloccal Peroxidase Inhibitor SPIN from Staphylococcus aureus
[[Category: Unreleased Structures]]
[[Category: Pfanzagl, V]]
[[Category: Brito, J.A]]