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==Crystal Structure of the Human mitochondrial Cysteine Desulfurase in complex with ISD11 and Iron-Sulfur Cluster Scaffold Protein ISCU1, and E. coli ACP1 protein at 3.15A==
==Crystal Structure of the Human mitochondrial Cysteine Desulfurase in complex with ISD11 and Iron-Sulfur Cluster Scaffold Protein ISCU1, and E. coli ACP1 protein at 3.15A==
<StructureSection load='5wkp' size='340' side='right' caption='[[5wkp]], [[Resolution|resolution]] 3.15&Aring;' scene=''>
<StructureSection load='5wkp' size='340' side='right'caption='[[5wkp]], [[Resolution|resolution]] 3.15&Aring;' scene=''>
== Structural highlights ==
== Structural highlights ==
<table><tr><td colspan='2'>[[5wkp]] is a 8 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5WKP OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5WKP FirstGlance]. <br>
<table><tr><td colspan='2'>[[5wkp]] is a 8 chain structure with sequence from [https://en.wikipedia.org/wiki/Escherichia_coli Escherichia coli] 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=5WKP OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5WKP FirstGlance]. <br>
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><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></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]] 3.15&#8491;</td></tr>
<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[5wlw|5wlw]]</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></td></tr>
<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Cysteine_desulfurase Cysteine desulfurase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.8.1.7 2.8.1.7] </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=5wkp FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5wkp OCA], [https://pdbe.org/5wkp PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5wkp RCSB], [https://www.ebi.ac.uk/pdbsum/5wkp PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5wkp ProSAT]</span></td></tr>
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5wkp FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5wkp OCA], [http://pdbe.org/5wkp PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5wkp RCSB], [http://www.ebi.ac.uk/pdbsum/5wkp PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5wkp ProSAT]</span></td></tr>
</table>
</table>
== Disease ==
== Disease ==
[[http://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. [[http://www.uniprot.org/uniprot/NFS1_HUMAN NFS1_HUMAN]] Severe neonatal lactic acidosis due to NFS1-ISD11 complex deficiency.  [[http://www.uniprot.org/uniprot/LYRM4_HUMAN LYRM4_HUMAN]] Severe neonatal lactic acidosis due to NFS1-ISD11 complex deficiency. The disease is caused by mutations affecting the gene represented in this entry.  
[https://www.uniprot.org/uniprot/NFS1_HUMAN NFS1_HUMAN] Severe neonatal lactic acidosis due to NFS1-ISD11 complex deficiency.  
== Function ==
== Function ==
[[http://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>  [[http://www.uniprot.org/uniprot/NFS1_HUMAN NFS1_HUMAN]] Catalyzes the removal of elemental sulfur from cysteine to produce alanine. It supplies the inorganic sulfur for iron-sulfur (Fe-S) clusters. May be involved in the biosynthesis of molybdenum cofactor.<ref>PMID:18650437</ref> [[http://www.uniprot.org/uniprot/ACP_ECO45 ACP_ECO45]] Carrier of the growing fatty acid chain in fatty acid biosynthesis.[HAMAP-Rule:MF_01217] [[http://www.uniprot.org/uniprot/LYRM4_HUMAN LYRM4_HUMAN]] Required for nuclear and mitochondrial iron-sulfur protein biosynthesis.<ref>PMID:17331979</ref> <ref>PMID:19454487</ref> 
[https://www.uniprot.org/uniprot/NFS1_HUMAN NFS1_HUMAN] Catalyzes the removal of elemental sulfur from cysteine to produce alanine. It supplies the inorganic sulfur for iron-sulfur (Fe-S) clusters. May be involved in the biosynthesis of molybdenum cofactor.<ref>PMID:18650437</ref>  
<div style="background-color:#fffaf0;">
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
== Publication Abstract from PubMed ==
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</div>
</div>
<div class="pdbe-citations 5wkp" style="background-color:#fffaf0;"></div>
<div class="pdbe-citations 5wkp" style="background-color:#fffaf0;"></div>
==See Also==
*[[Acyl carrier protein 3D structures|Acyl carrier protein 3D structures]]
*[[Cysteine desulfurase 3D structures|Cysteine desulfurase 3D structures]]
== References ==
== References ==
<references/>
<references/>
__TOC__
__TOC__
</StructureSection>
</StructureSection>
[[Category: Cysteine desulfurase]]
[[Category: Escherichia coli]]
[[Category: Boniecki, M T]]
[[Category: Homo sapiens]]
[[Category: Cygler, M]]
[[Category: Large Structures]]
[[Category: Transferase]]
[[Category: Boniecki MT]]
[[Category: Cygler M]]

Latest revision as of 17:15, 4 October 2023

Crystal Structure of the Human mitochondrial Cysteine Desulfurase in complex with ISD11 and Iron-Sulfur Cluster Scaffold Protein ISCU1, and E. coli ACP1 protein at 3.15ACrystal Structure of the Human mitochondrial Cysteine Desulfurase in complex with ISD11 and Iron-Sulfur Cluster Scaffold Protein ISCU1, and E. coli ACP1 protein at 3.15A

Structural highlights

5wkp is a 8 chain structure with sequence from Escherichia coli and Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:X-ray diffraction, Resolution 3.15Å
Ligands:,
Resources:FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Disease

NFS1_HUMAN Severe neonatal lactic acidosis due to NFS1-ISD11 complex deficiency.

Function

NFS1_HUMAN Catalyzes the removal of elemental sulfur from cysteine to produce alanine. It supplies the inorganic sulfur for iron-sulfur (Fe-S) clusters. May be involved in the biosynthesis of molybdenum cofactor.[1]

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[2]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

See Also

References

  1. ↑ Marelja Z, Stocklein W, Nimtz M, Leimkuhler S. A novel role for human Nfs1 in the cytoplasm: Nfs1 acts as a sulfur donor for MOCS3, a protein involved in molybdenum cofactor biosynthesis. J Biol Chem. 2008 Sep 12;283(37):25178-85. doi: 10.1074/jbc.M804064200. Epub 2008, Jul 23. PMID:18650437 doi:http://dx.doi.org/10.1074/jbc.M804064200
  2. ↑ Boniecki MT, Freibert SA, Muhlenhoff U, Lill R, Cygler M. Structure and functional dynamics of the mitochondrial Fe/S cluster synthesis complex. Nat Commun. 2017 Nov 3;8(1):1287. doi: 10.1038/s41467-017-01497-1. PMID:29097656 doi:http://dx.doi.org/10.1038/s41467-017-01497-1

5wkp, resolution 3.15Å

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