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| | ==Solution structure of the A147T variant of the mitochondrial translocator protein (tspo) in complex with pk11195== | | ==Solution structure of the A147T variant of the mitochondrial translocator protein (tspo) in complex with pk11195== |
| - | <StructureSection load='2n02' size='340' side='right'caption='[[2n02]], [[NMR_Ensembles_of_Models | 20 NMR models]]' scene=''> | + | <StructureSection load='2n02' size='340' side='right'caption='[[2n02]]' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[2n02]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Lk3_transgenic_mice Lk3 transgenic mice]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2N02 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2N02 FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[2n02]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Mus_musculus Mus musculus]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2N02 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2N02 FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=PKA:N-[(2R)-BUTAN-2-YL]-1-(2-CHLOROPHENYL)-N-METHYLISOQUINOLINE-3-CARBOXAMIDE'>PKA</scene></td></tr> | + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">Solution NMR</td></tr> |
| - | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat"><div style='overflow: auto; max-height: 3em;'>[[2mgy|2mgy]]</div></td></tr> | + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=PKA:N-[(2R)-BUTAN-2-YL]-1-(2-CHLOROPHENYL)-N-METHYLISOQUINOLINE-3-CARBOXAMIDE'>PKA</scene></td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">Bzrp, Tspo ([https://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=10090 LK3 transgenic mice])</td></tr>
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| | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=2n02 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2n02 OCA], [https://pdbe.org/2n02 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2n02 RCSB], [https://www.ebi.ac.uk/pdbsum/2n02 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2n02 ProSAT]</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=2n02 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2n02 OCA], [https://pdbe.org/2n02 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2n02 RCSB], [https://www.ebi.ac.uk/pdbsum/2n02 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2n02 ProSAT]</span></td></tr> |
| | </table> | | </table> |
| | + | == Function == |
| | + | [https://www.uniprot.org/uniprot/TSPO_MOUSE TSPO_MOUSE] Can bind protoporphyrin IX and may play a role in the transport of porphyrins and heme (By similarity). Was initially identified as peripheral-type benzodiazepine receptor; can also bind isoquinoline carboxamides. Promotes the transport of cholesterol across mitochondrial membranes and may play a role in lipid metabolism (PubMed:9832438, PubMed:24814875), but its precise physiological role is controversial. According to some reports, it is not required for steroid hormone biosynthesis (PubMed:24174323, PubMed:24936060).<ref>PMID:24174323</ref> <ref>PMID:24814875</ref> <ref>PMID:24936060</ref> <ref>PMID:8114671</ref> <ref>PMID:9832438</ref> |
| | <div style="background-color:#fffaf0;"> | | <div style="background-color:#fffaf0;"> |
| | == Publication Abstract from PubMed == | | == Publication Abstract from PubMed == |
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| | </StructureSection> | | </StructureSection> |
| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| - | [[Category: Lk3 transgenic mice]] | + | [[Category: Mus musculus]] |
| - | [[Category: Becker, S]] | + | [[Category: Becker S]] |
| - | [[Category: Giller, K]] | + | [[Category: Giller K]] |
| - | [[Category: Jaremko, L]] | + | [[Category: Jaremko L]] |
| - | [[Category: Jaremko, M]] | + | [[Category: Jaremko M]] |
| - | [[Category: Zweckstetter, M]] | + | [[Category: Zweckstetter M]] |
| - | [[Category: A147t]]
| + | |
| - | [[Category: Membrane protein]]
| + | |
| - | [[Category: Mitochondria]]
| + | |
| - | [[Category: Peripheral benzodiazepine receptor]]
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| - | [[Category: Pk11195]]
| + | |
| - | [[Category: Protein-ligand complex]]
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| Structural highlights
Function
TSPO_MOUSE Can bind protoporphyrin IX and may play a role in the transport of porphyrins and heme (By similarity). Was initially identified as peripheral-type benzodiazepine receptor; can also bind isoquinoline carboxamides. Promotes the transport of cholesterol across mitochondrial membranes and may play a role in lipid metabolism (PubMed:9832438, PubMed:24814875), but its precise physiological role is controversial. According to some reports, it is not required for steroid hormone biosynthesis (PubMed:24174323, PubMed:24936060).[1] [2] [3] [4] [5]
Publication Abstract from PubMed
Ligands of the transmembrane protein TSPO are used for imaging of brain inflammation, but a common polymorphism in TSPO complicates their application to humans. Here we determined the three-dimensional structure and side chain dynamics of the A147T polymorph of mammalian TSPO in complex with the first-generation ligand PK11195. We show that A147T TSPO is able to retain the same structural and dynamic profile of the wild-type protein and thus binds PK11195 with comparable affinity. Our study is important for the design of more potent diagnostic and therapeutic ligands of TSPO.
Structural integrity of the A147T polymorph of mammalian TSPO.,Jaremko M, Jaremko L, Giller K, Becker S, Zweckstetter M Chembiochem. 2015 May 12. doi: 10.1002/cbic.201500217. PMID:25974690[6]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Morohaku K, Pelton SH, Daugherty DJ, Butler WR, Deng W, Selvaraj V. Translocator protein/peripheral benzodiazepine receptor is not required for steroid hormone biosynthesis. Endocrinology. 2014 Jan;155(1):89-97. PMID:24174323 doi:10.1210/en.2013-1556
- ↑ Taylor JM, Allen AM, Graham A. Targeting mitochondrial 18 kDa translocator protein (TSPO) regulates macrophage cholesterol efflux and lipid phenotype. Clin Sci (Lond). 2014 Nov;127(10):603-13. PMID:24814875 doi:10.1042/CS20140047
- ↑ Tu LN, Morohaku K, Manna PR, Pelton SH, Butler WR, Stocco DM, Selvaraj V. Peripheral benzodiazepine receptor/translocator protein global knock-out mice are viable with no effects on steroid hormone biosynthesis. J Biol Chem. 2014 Oct 3;289(40):27444-54. PMID:24936060 doi:10.1074/jbc.M114.578286
- ↑ Garnier M, Dimchev AB, Boujrad N, Price JM, Musto NA, Papadopoulos V. In vitro reconstitution of a functional peripheral-type benzodiazepine receptor from mouse Leydig tumor cells. Mol Pharmacol. 1994 Feb;45(2):201-11 PMID:8114671
- ↑ Li H, Papadopoulos V. Peripheral-type benzodiazepine receptor function in cholesterol transport. Identification of a putative cholesterol recognition/interaction amino acid sequence and consensus pattern. Endocrinology. 1998 Dec;139(12):4991-7. PMID:9832438 doi:10.1210/endo.139.12.6390
- ↑ Jaremko M, Jaremko L, Giller K, Becker S, Zweckstetter M. Structural integrity of the A147T polymorph of mammalian TSPO. Chembiochem. 2015 May 12. doi: 10.1002/cbic.201500217. PMID:25974690 doi:http://dx.doi.org/10.1002/cbic.201500217
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