4zl4

From Proteopedia

(Difference between revisions)

Current revision

Plasmepsin V from Plasmodium vivax bound to a transition state mimetic (WEHI-842)

Structural highlights

4zl4 is a 2 chain structure with sequence from Plasmodium vivax. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:	X-ray diffraction, Resolution 2.37Å
Ligands:	, , ,
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

PLM5_PLAVS During the asexual blood stage, plays an essential role in the export of several proteins into the host erythrocytes by cleaving the pentameric localization motif RxLxE/Q/D (termed Plasmodium export element (PEXEL)) located downstream of the N-terminal secretory signal sequence (PubMed:24983235). Specifically, cleaves after the leucine residue in the RxLxE/Q/D (or RxLxxE) motif of exported proteins including EMP1 (By similarity). Also, by regulating protein export, plays an essential role in gametocyte development and thus parasite transmission to the mosquito vector (By similarity).[UniProtKB:Q8I6Z5][UniProtKB:W7JPD9]^[1]

Publication Abstract from PubMed

Plasmepsin V, an essential aspartyl protease of malaria parasites, has a key role in the export of effector proteins to parasite-infected erythrocytes. Consequently, it is an important drug target for the two most virulent malaria parasites of humans, Plasmodium falciparum and Plasmodium vivax. We developed a potent inhibitor of plasmepsin V, called WEHI-842, which directly mimics the Plasmodium export element (PEXEL). WEHI-842 inhibits recombinant plasmepsin V with a half-maximal inhibitory concentration of 0.2 nM, efficiently blocks protein export and inhibits parasite growth. We obtained the structure of P. vivax plasmepsin V in complex with WEHI-842 to 2.4-A resolution, which provides an explanation for the strict requirements for substrate and inhibitor binding. The structure characterizes both a plant-like fold and a malaria-specific helix-turn-helix motif that are likely to be important in cleavage of effector substrates for export.

Structural basis for plasmepsin V inhibition that blocks export of malaria proteins to human erythrocytes.,Hodder AN, Sleebs BE, Czabotar PE, Gazdik M, Xu Y, O'Neill MT, Lopaticki S, Nebl T, Triglia T, Smith BJ, Lowes K, Boddey JA, Cowman AF Nat Struct Mol Biol. 2015 Aug;22(8):590-6. doi: 10.1038/nsmb.3061. Epub 2015 Jul , 27. PMID:26214367^[2]

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

References

↑ Sleebs BE, Lopaticki S, Marapana DS, O'Neill MT, Rajasekaran P, Gazdik M, Günther S, Whitehead LW, Lowes KN, Barfod L, Hviid L, Shaw PJ, Hodder AN, Smith BJ, Cowman AF, Boddey JA. Inhibition of Plasmepsin V activity demonstrates its essential role in protein export, PfEMP1 display, and survival of malaria parasites. PLoS Biol. 2014 Jul 1;12(7):e1001897. PMID:24983235 doi:10.1371/journal.pbio.1001897
↑ Hodder AN, Sleebs BE, Czabotar PE, Gazdik M, Xu Y, O'Neill MT, Lopaticki S, Nebl T, Triglia T, Smith BJ, Lowes K, Boddey JA, Cowman AF. Structural basis for plasmepsin V inhibition that blocks export of malaria proteins to human erythrocytes. Nat Struct Mol Biol. 2015 Aug;22(8):590-6. doi: 10.1038/nsmb.3061. Epub 2015 Jul , 27. PMID:26214367 doi:http://dx.doi.org/10.1038/nsmb.3061

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

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/4zl4"

@@ Line 3: / Line 3: @@
 <StructureSection load='4zl4' size='340' side='right'caption='[[4zl4]], [[Resolution|resolution]] 2.37&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[4zl4]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Haemamoeba_vivax Haemamoeba vivax]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4ZL4 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4ZL4 FirstGlance]. <br>
+<table><tr><td colspan='2'>[[4zl4]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Plasmodium_vivax Plasmodium vivax]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4ZL4 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4ZL4 FirstGlance]. <br>
-</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=4PF:(2R)-1-[(2R)-2-(2-METHOXYETHOXY)PROPOXY]PROPAN-2-AMINE'>4PF</scene>, <scene name='pdbligand=4PK:N-[(BENZYLOXY)CARBONYL]-O-CARBAMIMIDAMIDO-L-HOMOSERYL-N-{(3S,4S)-3-HYDROXY-6-METHYL-1-OXO-1-[(2-PHENYLETHYL)AMINO]HEPTAN-4-YL}-L-VALINAMIDE'>4PK</scene>, <scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</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]] 2.37&#8491;</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=4zl4 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4zl4 OCA], [http://pdbe.org/4zl4 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4zl4 RCSB], [http://www.ebi.ac.uk/pdbsum/4zl4 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4zl4 ProSAT]</span></td></tr>
+<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=4PF:(2R)-1-[(2R)-2-(2-METHOXYETHOXY)PROPOXY]PROPAN-2-AMINE'>4PF</scene>, <scene name='pdbligand=4PK:N-[(BENZYLOXY)CARBONYL]-O-CARBAMIMIDAMIDO-L-HOMOSERYL-N-{(3S,4S)-3-HYDROXY-6-METHYL-1-OXO-1-[(2-PHENYLETHYL)AMINO]HEPTAN-4-YL}-L-VALINAMIDE'>4PK</scene>, <scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</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=4zl4 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4zl4 OCA], [https://pdbe.org/4zl4 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4zl4 RCSB], [https://www.ebi.ac.uk/pdbsum/4zl4 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4zl4 ProSAT]</span></td></tr>
 </table>
+== Function ==
+[https://www.uniprot.org/uniprot/PLM5_PLAVS PLM5_PLAVS] During the asexual blood stage, plays an essential role in the export of several proteins into the host erythrocytes by cleaving the pentameric localization motif RxLxE/Q/D (termed Plasmodium export element (PEXEL)) located downstream of the N-terminal secretory signal sequence (PubMed:24983235). Specifically, cleaves after the leucine residue in the RxLxE/Q/D (or RxLxxE) motif of exported proteins including EMP1 (By similarity). Also, by regulating protein export, plays an essential role in gametocyte development and thus parasite transmission to the mosquito vector (By similarity).[UniProtKB:Q8I6Z5][UniProtKB:W7JPD9]<ref>PMID:24983235</ref>
 <div style="background-color:#fffaf0;">
 == Publication Abstract from PubMed ==
@@ Line 16: / Line 19: @@
 </div>
 <div class="pdbe-citations 4zl4" style="background-color:#fffaf0;"></div>
+==See Also==
+*[[Plasmepsin|Plasmepsin]]
 == References ==
 <references/>
 __TOC__
 </StructureSection>
-[[Category: Haemamoeba vivax]]
 [[Category: Large Structures]]
-[[Category: Boddey, J A]]
+[[Category: Plasmodium vivax]]
-[[Category: Cowman, A F]]
+[[Category: Boddey JA]]
-[[Category: Czabotar, P E]]
+[[Category: Cowman AF]]
-[[Category: Gazdic, M]]
+[[Category: Czabotar PE]]
-[[Category: Hodder, A N]]
+[[Category: Gazdic M]]
-[[Category: Sleebs, B E]]
+[[Category: Hodder AN]]
-[[Category: Smith, B J]]
+[[Category: Sleebs BE]]
-[[Category: Aspartyl protease]]
+[[Category: Smith BJ]]
-[[Category: Hydrolase-hydrolase inhibitor complex]]
-[[Category: Inhibitor]]
-[[Category: Malaria]]
-[[Category: Pexel]]

4zl4

From Proteopedia

Current revision

Plasmepsin V from Plasmodium vivax bound to a transition state mimetic (WEHI-842)

Structural highlights

Function

Publication Abstract from PubMed

See Also

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

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