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| | ==Crystal structure of P. falciparum LipL1 in complex lipoate== | | ==Crystal structure of P. falciparum LipL1 in complex lipoate== |
| - | <StructureSection load='5t8u' size='340' side='right' caption='[[5t8u]], [[Resolution|resolution]] 2.32Å' scene=''> | + | <StructureSection load='5t8u' size='340' side='right'caption='[[5t8u]], [[Resolution|resolution]] 2.32Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[5t8u]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Plaf7 Plaf7]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5T8U OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5T8U FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[5t8u]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Plasmodium_falciparum_3D7 Plasmodium falciparum 3D7]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5T8U OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5T8U FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=LPA:LIPOIC+ACID'>LPA</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]] 2.324Å</td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">PF3D7_1314600 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=36329 PLAF7])</td></tr>
| + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=LPA:LIPOIC+ACID'>LPA</scene></td></tr> |
| - | <tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Transferase Transferase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.7.63 2.7.7.63] </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=5t8u FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5t8u OCA], [https://pdbe.org/5t8u PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5t8u RCSB], [https://www.ebi.ac.uk/pdbsum/5t8u PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5t8u 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=5t8u FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5t8u OCA], [http://pdbe.org/5t8u PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5t8u RCSB], [http://www.ebi.ac.uk/pdbsum/5t8u PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5t8u ProSAT]</span></td></tr> | + | |
| | </table> | | </table> |
| | + | == Function == |
| | + | [https://www.uniprot.org/uniprot/LIPLA_PLAF7 LIPLA_PLAF7] Catalyzes both the ATP-dependent activation of exogenously supplied lipoate to lipoyl-AMP and the transfer of the activated lipoyl onto the lipoyl domains of lipoate-dependent enzymes (PubMed:17244193, PubMed:25116855, PubMed:28543853). In the mitochondrion, functions as a redox switch between two lipoylation routes (PubMed:25116855). Senses the oxidation state of lipoate and determines which downstream enzymes will be lipoylated (PubMed:25116855). In low reducing conditions, uses lipoate in its oxidized ring form to lipoylate glycine cleavage system H-protein GCVH (PubMed:17244193, PubMed:25116855, PubMed:28543853). In high reducing conditions and together with LipL2, uses reduced lipoate (dihydrolipoate) to lipoylate the E2 component of the branched chain alpha-ketoacid dehydrogenase complex BCKDH-E2/BCDH and the E2 component of the alpha-ketoglutarate dehydrogenase complex KDH. LipL1 is responsible for catalysing the activation of lipoate, forming lipoyl-AMP while LipL2 is required but is not capable of catalyzing this reaction (PubMed:17244193, PubMed:25116855).<ref>PMID:17244193</ref> <ref>PMID:25116855</ref> <ref>PMID:28543853</ref> |
| | <div style="background-color:#fffaf0;"> | | <div style="background-color:#fffaf0;"> |
| | == Publication Abstract from PubMed == | | == Publication Abstract from PubMed == |
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| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Plaf7]] | + | [[Category: Large Structures]] |
| - | [[Category: Transferase]] | + | [[Category: Plasmodium falciparum 3D7]] |
| - | [[Category: Afanador, G A]] | + | [[Category: Afanador GA]] |
| - | [[Category: Guerra, A J]] | + | [[Category: Guerra AJ]] |
| - | [[Category: Prigge, S T]] | + | [[Category: Prigge ST]] |
| - | [[Category: Ligase]]
| + | |
| - | [[Category: Lipoylation]]
| + | |
| Structural highlights
Function
LIPLA_PLAF7 Catalyzes both the ATP-dependent activation of exogenously supplied lipoate to lipoyl-AMP and the transfer of the activated lipoyl onto the lipoyl domains of lipoate-dependent enzymes (PubMed:17244193, PubMed:25116855, PubMed:28543853). In the mitochondrion, functions as a redox switch between two lipoylation routes (PubMed:25116855). Senses the oxidation state of lipoate and determines which downstream enzymes will be lipoylated (PubMed:25116855). In low reducing conditions, uses lipoate in its oxidized ring form to lipoylate glycine cleavage system H-protein GCVH (PubMed:17244193, PubMed:25116855, PubMed:28543853). In high reducing conditions and together with LipL2, uses reduced lipoate (dihydrolipoate) to lipoylate the E2 component of the branched chain alpha-ketoacid dehydrogenase complex BCKDH-E2/BCDH and the E2 component of the alpha-ketoglutarate dehydrogenase complex KDH. LipL1 is responsible for catalysing the activation of lipoate, forming lipoyl-AMP while LipL2 is required but is not capable of catalyzing this reaction (PubMed:17244193, PubMed:25116855).[1] [2] [3]
Publication Abstract from PubMed
Plasmodium falciparum lipoate protein ligase 1 (PfLipL1) is an ATP-dependent ligase that belongs to the biotin/lipoate A/B protein ligase family (PFAM PF03099). PfLipL1 is the only known canonical lipoate ligase in Pf and functions as a redox switch between two lipoylation routes in the parasite mitochondrion. Here, we report the crystal structure of a deletion construct of PfLipL1 (PfLipL1Delta243-279 ) bound to lipoate, and validate the lipoylation activity of this construct in both an in vitro lipoylation assay and a cell-based lipoylation assay. This characterization represents the first step in understanding the redox dependence of the lipoylation mechanism in malaria parasites. Proteins 2017. (c) 2017 Wiley Periodicals, Inc.
Crystal structure of lipoate-bound lipoate ligase 1, LipL1, from Plasmodium falciparum.,Guerra AJ, Afanador GA, Prigge ST Proteins. 2017 May 24. doi: 10.1002/prot.25324. PMID:28543853[4]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Allary M, Lu JZ, Zhu L, Prigge ST. Scavenging of the cofactor lipoate is essential for the survival of the malaria parasite Plasmodium falciparum. Mol Microbiol. 2007 Mar;63(5):1331-44. PMID:17244193 doi:10.1111/j.1365-2958.2007.05592.x
- ↑ Afanador GA, Matthews KA, Bartee D, Gisselberg JE, Walters MS, Freel Meyers CL, Prigge ST. Redox-dependent lipoylation of mitochondrial proteins in Plasmodium falciparum. Mol Microbiol. 2014 Oct;94(1):156-71. PMID:25116855 doi:10.1111/mmi.12753
- ↑ Guerra AJ, Afanador GA, Prigge ST. Crystal structure of lipoate-bound lipoate ligase 1, LipL1, from Plasmodium falciparum. Proteins. 2017 May 24. doi: 10.1002/prot.25324. PMID:28543853 doi:http://dx.doi.org/10.1002/prot.25324
- ↑ Guerra AJ, Afanador GA, Prigge ST. Crystal structure of lipoate-bound lipoate ligase 1, LipL1, from Plasmodium falciparum. Proteins. 2017 May 24. doi: 10.1002/prot.25324. PMID:28543853 doi:http://dx.doi.org/10.1002/prot.25324
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