8yoq: Difference between revisions

Latest revision as of 07:56, 9 January 2025

Crystal structure of hFSP1 with both 6-OH-FAD and NADP (hFSP1-6-OH-FAD-NADP)

Structural highlights

8yoq is a 1 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:	X-ray diffraction, Resolution 1.79Å
Ligands:	6FA, NDP, SO4
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

FSP1_HUMAN A NAD(P)H-dependent oxidoreductase that acts as a key inhibitor of ferroptosis (PubMed:31634899, PubMed:31634900, PubMed:35922516). At the plasma membrane, catalyzes reduction of coenzyme Q/ubiquinone-10 to ubiquinol-10, a lipophilic radical-trapping antioxidant that prevents lipid oxidative damage and consequently ferroptosis (PubMed:31634899, PubMed:31634900). Acts in parallel to GPX4 to suppress phospholipid peroxidation and ferroptosis (PubMed:31634899, PubMed:31634900). This anti-ferroptotic function is independent of cellular glutathione levels (PubMed:31634899, PubMed:31634900). Also acts as a potent radical-trapping antioxidant by mediating warfarin-resistant vitamin K reduction in the canonical vitamin K cycle: catalyzes NAD(P)H-dependent reduction of vitamin K (phylloquinone, menaquinone-4 and menadione) to hydroquinone forms (PubMed:35922516). Hydroquinones act as potent radical-trapping antioxidants inhibitor of phospholipid peroxidation and ferroptosis (PubMed:35922516). May play a role in mitochondrial stress signaling (PubMed:26689472). Upon oxidative stress, associates with the lipid peroxidation end product 4-hydroxy-2-nonenal (HNE) forming a lipid adduct devoid of oxidoreductase activity, which then translocates from mitochondria into the nucleus triggering DNA damage and cell death (PubMed:26689472). Capable of DNA binding in a non-sequence specific way (PubMed:15958387).^[1] ^[2] ^[3] ^[4] ^[5]

References

↑ Marshall KR, Gong M, Wodke L, Lamb JH, Jones DJ, Farmer PB, Scrutton NS, Munro AW. The human apoptosis-inducing protein AMID is an oxidoreductase with a modified flavin cofactor and DNA binding activity. J Biol Chem. 2005 Sep 2;280(35):30735-40. PMID:15958387 doi:10.1074/jbc.M414018200
↑ Miriyala S, Thippakorn C, Chaiswing L, Xu Y, Noel T, Tovmasyan A, Batinic-Haberle I, Vander Kooi CW, Chi W, Latif AA, Panchatcharam M, Prachayasittikul V, Butterfield DA, Vore M, Moscow J, St Clair DK. Novel role of 4-hydroxy-2-nonenal in AIFm2-mediated mitochondrial stress signaling. Free Radic Biol Med. 2016 Feb;91:68-80. PMID:26689472 doi:10.1016/j.freeradbiomed.2015.12.002
↑ Doll S, Freitas FP, Shah R, Aldrovandi M, da Silva MC, Ingold I, Goya Grocin A, Xavier da Silva TN, Panzilius E, Scheel CH, Mourão A, Buday K, Sato M, Wanninger J, Vignane T, Mohana V, Rehberg M, Flatley A, Schepers A, Kurz A, White D, Sauer M, Sattler M, Tate EW, Schmitz W, Schulze A, O'Donnell V, Proneth B, Popowicz GM, Pratt DA, Angeli JPF, Conrad M. FSP1 is a glutathione-independent ferroptosis suppressor. Nature. 2019 Nov;575(7784):693-698. PMID:31634899 doi:10.1038/s41586-019-1707-0
↑ Bersuker K, Hendricks JM, Li Z, Magtanong L, Ford B, Tang PH, Roberts MA, Tong B, Maimone TJ, Zoncu R, Bassik MC, Nomura DK, Dixon SJ, Olzmann JA. The CoQ oxidoreductase FSP1 acts parallel to GPX4 to inhibit ferroptosis. Nature. 2019 Nov;575(7784):688-692. PMID:31634900 doi:10.1038/s41586-019-1705-2
↑ Mishima E, Ito J, Wu Z, Nakamura T, Wahida A, Doll S, Tonnus W, Nepachalovich P, Eggenhofer E, Aldrovandi M, Henkelmann B, Yamada KI, Wanninger J, Zilka O, Sato E, Feederle R, Hass D, Maida A, Mourão ASD, Linkermann A, Geissler EK, Nakagawa K, Abe T, Fedorova M, Proneth B, Pratt DA, Conrad M. A non-canonical vitamin K cycle is a potent ferroptosis suppressor. Nature. 2022 Aug;608(7924):778-783. PMID:35922516 doi:10.1038/s41586-022-05022-3

Proteopedia Page Contributors and Editors (what is this?)

OCA

[1] Marshall KR, Gong M, Wodke L, Lamb JH, Jones DJ, Farmer PB, Scrutton NS, Munro AW. The human apoptosis-inducing protein AMID is an oxidoreductase with a modified flavin cofactor and DNA binding activity. J Biol Chem. 2005 Sep 2;280(35):30735-40. PMID:15958387 doi:10.1074/jbc.M414018200

[2] Miriyala S, Thippakorn C, Chaiswing L, Xu Y, Noel T, Tovmasyan A, Batinic-Haberle I, Vander Kooi CW, Chi W, Latif AA, Panchatcharam M, Prachayasittikul V, Butterfield DA, Vore M, Moscow J, St Clair DK. Novel role of 4-hydroxy-2-nonenal in AIFm2-mediated mitochondrial stress signaling. Free Radic Biol Med. 2016 Feb;91:68-80. PMID:26689472 doi:10.1016/j.freeradbiomed.2015.12.002

[3] Doll S, Freitas FP, Shah R, Aldrovandi M, da Silva MC, Ingold I, Goya Grocin A, Xavier da Silva TN, Panzilius E, Scheel CH, Mourão A, Buday K, Sato M, Wanninger J, Vignane T, Mohana V, Rehberg M, Flatley A, Schepers A, Kurz A, White D, Sauer M, Sattler M, Tate EW, Schmitz W, Schulze A, O'Donnell V, Proneth B, Popowicz GM, Pratt DA, Angeli JPF, Conrad M. FSP1 is a glutathione-independent ferroptosis suppressor. Nature. 2019 Nov;575(7784):693-698. PMID:31634899 doi:10.1038/s41586-019-1707-0

[4] Bersuker K, Hendricks JM, Li Z, Magtanong L, Ford B, Tang PH, Roberts MA, Tong B, Maimone TJ, Zoncu R, Bassik MC, Nomura DK, Dixon SJ, Olzmann JA. The CoQ oxidoreductase FSP1 acts parallel to GPX4 to inhibit ferroptosis. Nature. 2019 Nov;575(7784):688-692. PMID:31634900 doi:10.1038/s41586-019-1705-2

[5] Mishima E, Ito J, Wu Z, Nakamura T, Wahida A, Doll S, Tonnus W, Nepachalovich P, Eggenhofer E, Aldrovandi M, Henkelmann B, Yamada KI, Wanninger J, Zilka O, Sato E, Feederle R, Hass D, Maida A, Mourão ASD, Linkermann A, Geissler EK, Nakagawa K, Abe T, Fedorova M, Proneth B, Pratt DA, Conrad M. A non-canonical vitamin K cycle is a potent ferroptosis suppressor. Nature. 2022 Aug;608(7924):778-783. PMID:35922516 doi:10.1038/s41586-022-05022-3

[1]

[2]

[3]

[4]

[5]

@@ Line 1: / Line 1: @@
-'''Unreleased structure'''
-The entry 8yoq is ON HOLD
+==Crystal structure of hFSP1 with both 6-OH-FAD and NADP (hFSP1-6-OH-FAD-NADP)==
+<StructureSection load='8yoq' size='340' side='right'caption='[[8yoq]], [[Resolution|resolution]] 1.79&Aring;' scene=''>
-Authors: Lan, H.Y., Gao, Y., Hong, T., Zhao, Z.Z., Chang, Z.H., Wang, Y.F., Wang, F.
+== Structural highlights ==
+<table><tr><td colspan='2'>[[8yoq]] 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=8YOQ OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=8YOQ FirstGlance]. <br>
-Description: Crystal structure of hFSP1 with both 6-OH-FAD and NADP (hFSP1-6-OH-FAD-NADP)
+</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.79&#8491;</td></tr>
-[[Category: Unreleased Structures]]
+<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=6FA:6-HYDROXY-FLAVIN-ADENINE+DINUCLEOTIDE'>6FA</scene>, <scene name='pdbligand=NDP:NADPH+DIHYDRO-NICOTINAMIDE-ADENINE-DINUCLEOTIDE+PHOSPHATE'>NDP</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></td></tr>
-[[Category: Gao, Y]]
+<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=8yoq FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=8yoq OCA], [https://pdbe.org/8yoq PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=8yoq RCSB], [https://www.ebi.ac.uk/pdbsum/8yoq PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=8yoq ProSAT]</span></td></tr>
-[[Category: Wang, F]]
+</table>
-[[Category: Wang, Y.F]]
+== Function ==
-[[Category: Lan, H.Y]]
+[https://www.uniprot.org/uniprot/FSP1_HUMAN FSP1_HUMAN] A NAD(P)H-dependent oxidoreductase that acts as a key inhibitor of ferroptosis (PubMed:31634899, PubMed:31634900, PubMed:35922516). At the plasma membrane, catalyzes reduction of coenzyme Q/ubiquinone-10 to ubiquinol-10, a lipophilic radical-trapping antioxidant that prevents lipid oxidative damage and consequently ferroptosis (PubMed:31634899, PubMed:31634900). Acts in parallel to GPX4 to suppress phospholipid peroxidation and ferroptosis (PubMed:31634899, PubMed:31634900). This anti-ferroptotic function is independent of cellular glutathione levels (PubMed:31634899, PubMed:31634900). Also acts as a potent radical-trapping antioxidant by mediating warfarin-resistant vitamin K reduction in the canonical vitamin K cycle: catalyzes NAD(P)H-dependent reduction of vitamin K (phylloquinone, menaquinone-4 and menadione) to hydroquinone forms (PubMed:35922516). Hydroquinones act as potent radical-trapping antioxidants inhibitor of phospholipid peroxidation and ferroptosis (PubMed:35922516). May play a role in mitochondrial stress signaling (PubMed:26689472). Upon oxidative stress, associates with the lipid peroxidation end product 4-hydroxy-2-nonenal (HNE) forming a lipid adduct devoid of oxidoreductase activity, which then translocates from mitochondria into the nucleus triggering DNA damage and cell death (PubMed:26689472). Capable of DNA binding in a non-sequence specific way (PubMed:15958387).<ref>PMID:15958387</ref> <ref>PMID:26689472</ref> <ref>PMID:31634899</ref> <ref>PMID:31634900</ref> <ref>PMID:35922516</ref>
-[[Category: Hong, T]]
+== References ==
-[[Category: Chang, Z.H]]
+<references/>
-[[Category: Zhao, Z.Z]]
+__TOC__
+</StructureSection>
+[[Category: Homo sapiens]]
+[[Category: Large Structures]]
+[[Category: Chang ZH]]
+[[Category: Gao Y]]
+[[Category: Hong T]]
+[[Category: Lan HY]]
+[[Category: Wang F]]
+[[Category: Wang YF]]
+[[Category: Zhao ZZ]]

8yoq: Difference between revisions

Latest revision as of 07:56, 9 January 2025

Crystal structure of hFSP1 with both 6-OH-FAD and NADP (hFSP1-6-OH-FAD-NADP)

Structural highlights

Function

References

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