4j4n: Difference between revisions

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'''Unreleased structure'''


The entry 4j4n is ON HOLD  until Paper Publication
==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]] 2.75&Aring;' scene=''>
== Structural highlights ==
<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='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.75&#8491;</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='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>
</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;">
== 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.


Authors: Sreekanth, R., Harikishore, A., Yoon, H.S.
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<ref>PMID:23974147</ref>


Description: Crystal structure of FK506 binding domain of plasmodium falciparum FKBP35 in complex with D44
From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 4j4n" style="background-color:#fffaf0;"></div>
 
==See Also==
*[[FKBP 3D structures|FKBP 3D structures]]
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Large Structures]]
[[Category: Plasmodium falciparum 3D7]]
[[Category: Harikishore A]]
[[Category: Sreekanth R]]
[[Category: Yoon HS]]

Latest revision as of 17:20, 8 November 2023

Crystal structure of FK506 binding domain of plasmodium falciparum FKBP35 in complex with D44Crystal structure of FK506 binding domain of plasmodium falciparum FKBP35 in complex with D44

Structural highlights

4j4n is a 3 chain structure with sequence from Plasmodium falciparum 3D7. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:X-ray diffraction, Resolution 2.75Å
Ligands:
Resources:FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

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

  1. ↑ 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
  2. ↑ 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
  3. ↑ 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
  4. ↑ 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
  5. ↑ 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

4j4n, resolution 2.75Å

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