9m3m: Difference between revisions

Latest revision as of 08:22, 13 August 2025

Structure of FSP1 in complex with FSEN1

Structural highlights

9m3m 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 2.01Å
Ligands:	6FA, A1EMU, NAP
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

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[2]

[3]

[4]

[5]

@@ Line 1: / Line 1: @@
-'''Unreleased structure'''
-The entry 9m3m is ON HOLD  until 2027-03-03
+==Structure of FSP1 in complex with FSEN1==
+<StructureSection load='9m3m' size='340' side='right'caption='[[9m3m]], [[Resolution|resolution]] 2.01&Aring;' scene=''>
-Authors: Zhang, S.T., Jia, D.
+== Structural highlights ==
+<table><tr><td colspan='2'>[[9m3m]] 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=9M3M OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=9M3M FirstGlance]. <br>
-Description: Structure of FSP1 in complex with FSEN1
+</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.01&#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=A1EMU:3-(4-bromophenyl)-6-[[4-(4-methoxyphenyl)piperazin-1-yl]methyl]-[1,3]thiazolo[2,3-c][1,2,4]triazole'>A1EMU</scene>, <scene name='pdbligand=NAP:NADP+NICOTINAMIDE-ADENINE-DINUCLEOTIDE+PHOSPHATE'>NAP</scene></td></tr>
-[[Category: Zhang, S.T]]
+<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=9m3m FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=9m3m OCA], [https://pdbe.org/9m3m PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=9m3m RCSB], [https://www.ebi.ac.uk/pdbsum/9m3m PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=9m3m ProSAT]</span></td></tr>
-[[Category: Jia, D]]
+</table>
+== Function ==
+[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>
+== References ==
+<references/>
+__TOC__
+</StructureSection>
+[[Category: Homo sapiens]]
+[[Category: Large Structures]]
+[[Category: Jia D]]
+[[Category: Zhang ST]]

9m3m: Difference between revisions

Latest revision as of 08:22, 13 August 2025

Structure of FSP1 in complex with FSEN1

Structural highlights

Function

References

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