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2vn1

From Proteopedia

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Current revision

Crystal structure of the FK506-binding domain of Plasmodium falciparum FKBP35 in complex with FK506

Structural highlights

2vn1 is a 2 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 2.35Å
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]

Evolutionary Conservation

Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.

Publication Abstract from PubMed

The emergence of multi-drug-resistant strains of Plasmodium parasites has prompted the search for alternative therapeutic strategies for combating malaria. One possible strategy is to exploit existing drugs as lead compounds. FK506 is currently used in the clinic for preventing transplant rejection. It binds to a alpha/beta protein module of approximately 120 amino acids known as the FK506 binding domain (FKBD), which is found in various organisms, including human, yeast, and Plasmodium falciparum (PfFKBD). Antiparasitic effects of FK506 and its analogues devoid of immunosuppressive activities have been demonstrated. We report here the crystallographic structure at 2.35 A resolution of PfFKBD complexed with FK506. Compared to the human FKBP12-FK506 complex reported earlier, the structure reveals structural differences in the beta5-beta6 segment that lines the FK506 binding site. The presence in PfFKBD of Cys-106 and Ser-109 (substituting for His-87 and Ile-90, respectively, in human FKBP12), which are 4-5 A from the nearest atom of the FK506 compound, suggests possible routes for the rational design of analogues of FK506 with specific antiparasitic activity. Upon ligand binding, several conformational changes occur in PfFKBD, including aromatic residues that shape the FK506 binding pocket as shown by NMR studies. A microarray analysis suggests that FK506 and cyclosporine A (CsA) might inhibit parasite development by interfering with the same signaling pathways.

Crystal Structure of the FK506 Binding Domain of Plasmodium falciparum FKBP35 in Complex with FK506.,Kotaka M, Ye H, Alag R, Hu G, Bozdech Z, Preiser PR, Yoon HS, Lescar J Biochemistry. 2008 May 9;. PMID:18465874^[5]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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
↑ Kotaka M, Ye H, Alag R, Hu G, Bozdech Z, Preiser PR, Yoon HS, Lescar J. Crystal Structure of the FK506 Binding Domain of Plasmodium falciparum FKBP35 in Complex with FK506. Biochemistry. 2008 May 9;. PMID:18465874 doi:10.1021/bi800004u

1 Structural highlights
2 Function
3 Evolutionary Conservation
4 Publication Abstract from PubMed
5 See Also
6 References

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/2vn1"

@@ Line 3: / Line 3: @@
 <StructureSection load='2vn1' size='340' side='right'caption='[[2vn1]], [[Resolution|resolution]] 2.35&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[2vn1]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Plaf7 Plaf7]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2VN1 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2VN1 FirstGlance]. <br>
+<table><tr><td colspan='2'>[[2vn1]] 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=2VN1 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2VN1 FirstGlance]. <br>
-</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=FK5:8-DEETHYL-8-[BUT-3-ENYL]-ASCOMYCIN'>FK5</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]] 2.35&#8491;</td></tr>
-<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat"><div style='overflow: auto; max-height: 3em;'>[[2fbn|2fbn]]</div></td></tr>
+<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=FK5:8-DEETHYL-8-[BUT-3-ENYL]-ASCOMYCIN'>FK5</scene></td></tr>
-<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[https://en.wikipedia.org/wiki/Peptidylprolyl_isomerase Peptidylprolyl isomerase], with EC number [https://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'>[https://proteopedia.org/fgij/fg.htm?mol=2vn1 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2vn1 OCA], [https://pdbe.org/2vn1 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2vn1 RCSB], [https://www.ebi.ac.uk/pdbsum/2vn1 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2vn1 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>
 == Evolutionary Conservation ==
 [[Image:Consurf_key_small.gif|200px|right]]
@@ Line 36: / Line 37: @@
 </StructureSection>
 [[Category: Large Structures]]
-[[Category: Peptidylprolyl isomerase]]
+[[Category: Plasmodium falciparum 3D7]]
-[[Category: Plaf7]]
+[[Category: Alag R]]
-[[Category: Alag, R]]
+[[Category: Kotaka M]]
-[[Category: Kotaka, M]]
+[[Category: Lescar J]]
-[[Category: Lescar, J]]
+[[Category: Preiser PR]]
-[[Category: Preiser, P R]]
+[[Category: Ye H]]
-[[Category: Ye, H]]
+[[Category: Yoon HS]]
-[[Category: Yoon, H S]]
-[[Category: Fk506]]
-[[Category: Fkbp]]
-[[Category: Isomerase]]
-[[Category: Plasmodium falciparum]]
-[[Category: Tpr repeat]]

2vn1

From Proteopedia

Current revision

Crystal structure of the FK506-binding domain of Plasmodium falciparum FKBP35 in complex with FK506

Structural highlights

Function

Evolutionary Conservation

Publication Abstract from PubMed

See Also

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

Views

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