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| | ==Crystal structure of FK506 binding domain of plasmodium falciparum FKBP35 in complex with D44== | | ==Crystal structure of FK506 binding domain of plasmodium falciparum FKBP35 in complex with D44== |
| - | <StructureSection load='4j4n' size='340' side='right' caption='[[4j4n]], [[Resolution|resolution]] 2.75Å' scene=''> | + | <StructureSection load='4j4n' size='340' side='right'caption='[[4j4n]], [[Resolution|resolution]] 2.75Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[4j4n]] is a 3 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=4J4N OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4J4N FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[4j4n]] is a 3 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=4J4N OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4J4N FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=D44:N-(2-ETHYLPHENYL)-2-(3H-IMIDAZO[4,5-B]PYRIDIN-2-YLSULFANYL)ACETAMIDE'>D44</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]] 2.75Å</td></tr> |
| - | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[2vn1|2vn1]], [[2ofn|2ofn]], [[4j4o|4j4o]]</td></tr>
| + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=D44:N-(2-ETHYLPHENYL)-2-(3H-IMIDAZO[4,5-B]PYRIDIN-2-YLSULFANYL)ACETAMIDE'>D44</scene></td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">FKBP35, PFL2275C ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=36329 PLAF7])</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=4j4n FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4j4n OCA], [https://pdbe.org/4j4n PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4j4n RCSB], [https://www.ebi.ac.uk/pdbsum/4j4n PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4j4n 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/Peptidylprolyl_isomerase Peptidylprolyl isomerase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=5.2.1.8 5.2.1.8] </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=4j4n FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4j4n OCA], [http://pdbe.org/4j4n PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4j4n RCSB], [http://www.ebi.ac.uk/pdbsum/4j4n PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4j4n ProSAT]</span></td></tr> | + | |
| | </table> | | </table> |
| | + | == Function == |
| | + | [https://www.uniprot.org/uniprot/FKB35_PLAF7 FKB35_PLAF7] Has peptidylprolyl isomerase (PPIase) and co-chaperone activities (PubMed:15664653, PubMed:15850699). Assists protein folding by catalyzing the peptidyl conversion of cis and trans rotamers of the prolyl amide bond of protein substrates (PubMed:15664653, PubMed:15850699, PubMed:23974147). Inhibits calcineurin phosphatase activity in vitro (PubMed:15850699, PubMed:17289400, PubMed:23974147). Plays an essential role in merozoite egress from host erythrocytes (PubMed:15664653, PubMed:23974147).<ref>PMID:15664653</ref> <ref>PMID:15850699</ref> <ref>PMID:17289400</ref> <ref>PMID:23974147</ref> |
| | <div style="background-color:#fffaf0;"> | | <div style="background-color:#fffaf0;"> |
| | == Publication Abstract from PubMed == | | == Publication Abstract from PubMed == |
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| | ==See Also== | | ==See Also== |
| - | *[[FK506 binding protein|FK506 binding protein]] | + | *[[FKBP 3D structures|FKBP 3D structures]] |
| | == References == | | == References == |
| | <references/> | | <references/> |
| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Peptidylprolyl isomerase]] | + | [[Category: Large Structures]] |
| - | [[Category: Plaf7]] | + | [[Category: Plasmodium falciparum 3D7]] |
| - | [[Category: Harikishore, A]] | + | [[Category: Harikishore A]] |
| - | [[Category: Sreekanth, R]] | + | [[Category: Sreekanth R]] |
| - | [[Category: Yoon, H S]] | + | [[Category: Yoon HS]] |
| - | [[Category: D44]]
| + | |
| - | [[Category: Fk506 binding]]
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| - | [[Category: Fkbp35]]
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| - | [[Category: Isomerase-isomerase inhibitor complex]]
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| Structural highlights
Function
FKB35_PLAF7 Has peptidylprolyl isomerase (PPIase) and co-chaperone activities (PubMed:15664653, PubMed:15850699). Assists protein folding by catalyzing the peptidyl conversion of cis and trans rotamers of the prolyl amide bond of protein substrates (PubMed:15664653, PubMed:15850699, PubMed:23974147). Inhibits calcineurin phosphatase activity in vitro (PubMed:15850699, PubMed:17289400, PubMed:23974147). Plays an essential role in merozoite egress from host erythrocytes (PubMed:15664653, PubMed:23974147).[1] [2] [3] [4]
Publication Abstract from PubMed
Malaria parasite strains have emerged to tolerate the therapeutic effects of the prophylactics and drugs presently available. This resistance now poses a serious challenge to researchers in the bid to overcome malaria parasitic infection. Recent studies have shown that FK520 and its analogs inhibit malaria parasites growth by binding to FK506 binding proteins (FKBPs) of the parasites. Structure based drug screening efforts based on three-dimensional structural information of FKBPs from Plasmodium falciparum led us to identify new chemical entities that bind to the parasite FKBP35 and inhibit its growth. Our experimental results verify that this novel compound (D44) modulate the PPIase activity of Plasmodium FKBP35 and demonstrate the stage-specific growth inhibition of Plasmodium falciparum strains. Here, we present the X-ray crystallographic structures of FK506 binding domains (FKBDs) of PfFKBP35 and PvFKBP35 in complex with the newly identified inhibitor providing molecular insights into its mode of action.
Small molecule Plasmodium FKBP35 inhibitor as a potential antimalaria agent.,Harikishore A, Niang M, Rajan S, Preiser PR, Yoon HS Sci Rep. 2013 Aug 26;3:2501. doi: 10.1038/srep02501. PMID:23974147[5]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Monaghan P, Bell A. A Plasmodium falciparum FK506-binding protein (FKBP) with peptidyl-prolyl cis-trans isomerase and chaperone activities. Mol Biochem Parasitol. 2005 Feb;139(2):185-95. doi:, 10.1016/j.molbiopara.2004.10.007. PMID:15664653 doi:http://dx.doi.org/10.1016/j.molbiopara.2004.10.007
- ↑ Kumar R, Adams B, Musiyenko A, Shulyayeva O, Barik S. The FK506-binding protein of the malaria parasite, Plasmodium falciparum, is a FK506-sensitive chaperone with FK506-independent calcineurin-inhibitory activity. Mol Biochem Parasitol. 2005 Jun;141(2):163-73. doi:, 10.1016/j.molbiopara.2005.02.007. Epub 2005 Mar 19. PMID:15850699 doi:http://dx.doi.org/10.1016/j.molbiopara.2005.02.007
- ↑ Yoon HR, Kang CB, Chia J, Tang K, Yoon HS. Expression, purification, and molecular characterization of Plasmodium falciparum FK506-binding protein 35 (PfFKBP35). Protein Expr Purif. 2007 May;53(1):179-85. doi: 10.1016/j.pep.2006.12.019. Epub, 2006 Dec 30. PMID:17289400 doi:http://dx.doi.org/10.1016/j.pep.2006.12.019
- ↑ Harikishore A, Niang M, Rajan S, Preiser PR, Yoon HS. Small molecule Plasmodium FKBP35 inhibitor as a potential antimalaria agent. Sci Rep. 2013 Aug 26;3:2501. doi: 10.1038/srep02501. PMID:23974147 doi:10.1038/srep02501
- ↑ Harikishore A, Niang M, Rajan S, Preiser PR, Yoon HS. Small molecule Plasmodium FKBP35 inhibitor as a potential antimalaria agent. Sci Rep. 2013 Aug 26;3:2501. doi: 10.1038/srep02501. PMID:23974147 doi:10.1038/srep02501
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