5wlw
From Proteopedia
(Difference between revisions)
(New page: '''Unreleased structure''' The entry 5wlw is ON HOLD until Paper Publication Authors: Boniecki, M.T., Cygler, M. Description: Crystal Structure of the Human Mitochondrial Cysteine Desu...) |
|||
| (3 intermediate revisions not shown.) | |||
| Line 1: | Line 1: | ||
| - | '''Unreleased structure''' | ||
| - | The entry | + | ==Crystal Structure of the Human Mitochondrial Cysteine Desulfurase with active Cysteine Loop within ISCU1 active site, coordinating Zn ion. Complexed with human ISD11 and E. coli ACP1 at 3.3A.== |
| + | <StructureSection load='5wlw' size='340' side='right'caption='[[5wlw]], [[Resolution|resolution]] 3.32Å' scene=''> | ||
| + | == Structural highlights == | ||
| + | <table><tr><td colspan='2'>[[5wlw]] is a 8 chain structure with sequence from [https://en.wikipedia.org/wiki/Escherichia_coli_S88 Escherichia coli S88] and [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5WLW OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5WLW 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]] 3.317Å</td></tr> | ||
| + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=8Q1:S-[2-({N-[(2R)-2-hydroxy-3,3-dimethyl-4-(phosphonooxy)butanoyl]-beta-alanyl}amino)ethyl]+dodecanethioate'>8Q1</scene>, <scene name='pdbligand=PLP:PYRIDOXAL-5-PHOSPHATE'>PLP</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</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=5wlw FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5wlw OCA], [https://pdbe.org/5wlw PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5wlw RCSB], [https://www.ebi.ac.uk/pdbsum/5wlw PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5wlw ProSAT]</span></td></tr> | ||
| + | </table> | ||
| + | == Disease == | ||
| + | [https://www.uniprot.org/uniprot/ISCU_HUMAN ISCU_HUMAN] Hereditary myopathy with lactic acidosis due to ISCU deficiency. The disease is caused by mutations affecting the gene represented in this entry. | ||
| + | == Function == | ||
| + | [https://www.uniprot.org/uniprot/ISCU_HUMAN ISCU_HUMAN] Scaffold protein for the de novo synthesis of iron-sulfur (Fe-S) clusters within mitochondria, which is required for maturation of both mitochondrial and cytoplasmic [2Fe-2S] and [4Fe-4S] proteins (PubMed:11060020). First, a [2Fe-2S] cluster is transiently assembled on the scaffold protein ISCU. In a second step, the cluster is released from ISCU, transferred to a glutaredoxin GLRX5, followed by the formation of mitochondrial [2Fe-2S] proteins, the synthesis of [4Fe-4S] clusters and their target-specific insertion into the recipient apoproteins. Cluster assembly on ISCU depends on the function of the cysteine desulfurase complex NFS1-LYRM4/ISD11, which serves as the sulfur donor for cluster synthesis, the iron-binding protein frataxin as the putative iron donor, and the electron transfer chain comprised of ferredoxin reductase and ferredoxin, which receive their electrons from NADH (By similarity).[UniProtKB:Q03020]<ref>PMID:11060020</ref> | ||
| + | <div style="background-color:#fffaf0;"> | ||
| + | == Publication Abstract from PubMed == | ||
| + | Iron-sulfur (Fe/S) clusters are essential protein cofactors crucial for many cellular functions including DNA maintenance, protein translation, and energy conversion. De novo Fe/S cluster synthesis occurs on the mitochondrial scaffold protein ISCU and requires cysteine desulfurase NFS1, ferredoxin, frataxin, and the small factors ISD11 and ACP (acyl carrier protein). Both the mechanism of Fe/S cluster synthesis and function of ISD11-ACP are poorly understood. Here, we present crystal structures of three different NFS1-ISD11-ACP complexes with and without ISCU, and we use SAXS analyses to define the 3D architecture of the complete mitochondrial Fe/S cluster biosynthetic complex. Our structural and biochemical studies provide mechanistic insights into Fe/S cluster synthesis at the catalytic center defined by the active-site Cys of NFS1 and conserved Cys, Asp, and His residues of ISCU. We assign specific regulatory rather than catalytic roles to ISD11-ACP that link Fe/S cluster synthesis with mitochondrial lipid synthesis and cellular energy status. | ||
| - | + | Structure and functional dynamics of the mitochondrial Fe/S cluster synthesis complex.,Boniecki MT, Freibert SA, Muhlenhoff U, Lill R, Cygler M Nat Commun. 2017 Nov 3;8(1):1287. doi: 10.1038/s41467-017-01497-1. PMID:29097656<ref>PMID:29097656</ref> | |
| - | + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |
| - | [[Category: | + | </div> |
| - | [[Category: | + | <div class="pdbe-citations 5wlw" style="background-color:#fffaf0;"></div> |
| - | [[Category: Boniecki | + | |
| + | ==See Also== | ||
| + | *[[Acyl carrier protein 3D structures|Acyl carrier protein 3D structures]] | ||
| + | *[[Cysteine desulfurase 3D structures|Cysteine desulfurase 3D structures]] | ||
| + | == References == | ||
| + | <references/> | ||
| + | __TOC__ | ||
| + | </StructureSection> | ||
| + | [[Category: Escherichia coli S88]] | ||
| + | [[Category: Homo sapiens]] | ||
| + | [[Category: Large Structures]] | ||
| + | [[Category: Boniecki MT]] | ||
| + | [[Category: Cygler M]] | ||
Current revision
Crystal Structure of the Human Mitochondrial Cysteine Desulfurase with active Cysteine Loop within ISCU1 active site, coordinating Zn ion. Complexed with human ISD11 and E. coli ACP1 at 3.3A.
| |||||||||||
