|
|
| Line 3: |
Line 3: |
| | <StructureSection load='5usr' size='340' side='right'caption='[[5usr]], [[Resolution|resolution]] 3.09Å' scene=''> | | <StructureSection load='5usr' size='340' side='right'caption='[[5usr]], [[Resolution|resolution]] 3.09Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[5usr]] is a 12 chain structure with sequence from [http://en.wikipedia.org/wiki/Ecoli Ecoli] and [http://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5USR OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5USR FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[5usr]] is a 12 chain structure with sequence from [https://en.wikipedia.org/wiki/Escherichia_coli_K-12 Escherichia coli K-12] 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=5USR OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5USR 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></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]] 3.09Å</td></tr> |
| - | <tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=LLP:(2S)-2-AMINO-6-[[3-HYDROXY-2-METHYL-5-(PHOSPHONOOXYMETHYL)PYRIDIN-4-YL]METHYLIDENEAMINO]HEXANOIC+ACID'>LLP</scene></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=LLP:(2S)-2-AMINO-6-[[3-HYDROXY-2-METHYL-5-(PHOSPHONOOXYMETHYL)PYRIDIN-4-YL]METHYLIDENEAMINO]HEXANOIC+ACID'>LLP</scene></td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">NFS1, NIFS, HUSSY-08 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN]), LYRM4, C6orf149, ISD11, CGI-203 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN]), acpP, b1094, JW1080 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=83333 ECOLI])</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=5usr FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5usr OCA], [https://pdbe.org/5usr PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5usr RCSB], [https://www.ebi.ac.uk/pdbsum/5usr PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5usr ProSAT]</span></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'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5usr FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5usr OCA], [http://pdbe.org/5usr PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5usr RCSB], [http://www.ebi.ac.uk/pdbsum/5usr PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5usr ProSAT]</span></td></tr> | + | |
| | </table> | | </table> |
| | == Disease == | | == Disease == |
| - | [[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/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. |
| | == Function == | | == Function == |
| - | [[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_ECOLI ACP_ECOLI]] 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/LYRM4_HUMAN LYRM4_HUMAN] Required for nuclear and mitochondrial iron-sulfur protein biosynthesis.<ref>PMID:17331979</ref> <ref>PMID:19454487</ref> |
| | <div style="background-color:#fffaf0;"> | | <div style="background-color:#fffaf0;"> |
| | == Publication Abstract from PubMed == | | == Publication Abstract from PubMed == |
| Line 31: |
Line 29: |
| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Cysteine desulfurase]] | + | [[Category: Escherichia coli K-12]] |
| - | [[Category: Ecoli]] | + | [[Category: Homo sapiens]] |
| - | [[Category: Human]]
| + | |
| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| - | [[Category: Barondeau, D P]] | + | [[Category: Barondeau DP]] |
| - | [[Category: Cory, S A]] | + | [[Category: Cory SA]] |
| - | [[Category: Acyl-carrier protein]]
| + | |
| - | [[Category: Fe-s cluster assembly]]
| + | |
| - | [[Category: Lyr]]
| + | |
| - | [[Category: Nfs1]]
| + | |
| - | [[Category: Transferase]]
| + | |
| Structural highlights
Disease
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.
Function
LYRM4_HUMAN Required for nuclear and mitochondrial iron-sulfur protein biosynthesis.[1] [2]
Publication Abstract from PubMed
In eukaryotes, sulfur is mobilized for incorporation into multiple biosynthetic pathways by a cysteine desulfurase complex that consists of a catalytic subunit (NFS1), LYR protein (ISD11), and acyl carrier protein (ACP). This NFS1-ISD11-ACP (SDA) complex forms the core of the iron-sulfur (Fe-S) assembly complex and associates with assembly proteins ISCU2, frataxin (FXN), and ferredoxin to synthesize Fe-S clusters. Here we present crystallographic and electron microscopic structures of the SDA complex coupled to enzyme kinetic and cell-based studies to provide structure-function properties of a mitochondrial cysteine desulfurase. Unlike prokaryotic cysteine desulfurases, the SDA structure adopts an unexpected architecture in which a pair of ISD11 subunits form the dimeric core of the SDA complex, which clarifies the critical role of ISD11 in eukaryotic assemblies. The different quaternary structure results in an incompletely formed substrate channel and solvent-exposed pyridoxal 5'-phosphate cofactor and provides a rationale for the allosteric activator function of FXN in eukaryotic systems. The structure also reveals the 4'-phosphopantetheine-conjugated acyl-group of ACP occupies the hydrophobic core of ISD11, explaining the basis of ACP stabilization. The unexpected architecture for the SDA complex provides a framework for understanding interactions with acceptor proteins for sulfur-containing biosynthetic pathways, elucidating mechanistic details of eukaryotic Fe-S cluster biosynthesis, and clarifying how defects in Fe-S cluster assembly lead to diseases such as Friedreich's ataxia. Moreover, our results support a lock-and-key model in which LYR proteins associate with acyl-ACP as a mechanism for fatty acid biosynthesis to coordinate the expression, Fe-S cofactor maturation, and activity of the respiratory complexes.
Structure of human Fe-S assembly subcomplex reveals unexpected cysteine desulfurase architecture and acyl-ACP-ISD11 interactions.,Cory SA, Van Vranken JG, Brignole EJ, Patra S, Winge DR, Drennan CL, Rutter J, Barondeau DP Proc Natl Acad Sci U S A. 2017 Jul 3;114(27):E5325-E5334. doi:, 10.1073/pnas.1702849114. Epub 2017 Jun 20. PMID:28634302[3]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Shan Y, Napoli E, Cortopassi G. Mitochondrial frataxin interacts with ISD11 of the NFS1/ISCU complex and multiple mitochondrial chaperones. Hum Mol Genet. 2007 Apr 15;16(8):929-41. Epub 2007 Mar 1. PMID:17331979 doi:http://dx.doi.org/ddm038
- ↑ Shi Y, Ghosh MC, Tong WH, Rouault TA. Human ISD11 is essential for both iron-sulfur cluster assembly and maintenance of normal cellular iron homeostasis. Hum Mol Genet. 2009 Aug 15;18(16):3014-25. doi: 10.1093/hmg/ddp239. Epub 2009 May, 18. PMID:19454487 doi:http://dx.doi.org/10.1093/hmg/ddp239
- ↑ Cory SA, Van Vranken JG, Brignole EJ, Patra S, Winge DR, Drennan CL, Rutter J, Barondeau DP. Structure of human Fe-S assembly subcomplex reveals unexpected cysteine desulfurase architecture and acyl-ACP-ISD11 interactions. Proc Natl Acad Sci U S A. 2017 Jul 3;114(27):E5325-E5334. doi:, 10.1073/pnas.1702849114. Epub 2017 Jun 20. PMID:28634302 doi:http://dx.doi.org/10.1073/pnas.1702849114
|
