1lf4

From Proteopedia

(Difference between revisions)

Current revision

STRUCTURE OF PLASMEPSIN II

Structural highlights

1lf4 is a 1 chain structure with sequence from Plasmodium falciparum. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:	X-ray diffraction, Resolution 1.9Å
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

PLM2_PLAFX During the asexual blood stage, participates in initial cleavage of native host hemoglobin (Hb) resulting in Hb denaturation (PubMed:8844673, PubMed:11782538, PubMed:15574427). May cleave preferentially denatured hemoglobin that has been cleaved by PMI (PubMed:8844673). Digestion of host Hb is an essential step which provides the parasite with amino acids for protein synthesis, and regulates osmolarity (Probable).^[1] ^[2] ^[3]

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

Malaria remains a human disease of global significance and a major cause of high infant mortality in endemic nations. Parasites of the genus Plasmodium cause the disease by degrading human hemoglobin as a source of amino acids for their growth and maturation. Hemoglobin degradation is initiated by aspartic proteases, termed plasmepsins, with a cleavage at the alpha-chain between residues Phe33 and Leu34. Plasmepsin II is one of the four catalytically active plasmepsins that has been identified in the food vacuole of Plasmodium falciparum. Novel crystal structures of uncomplexed plasmepsin II as well as the complex with a potent inhibitor have been refined with data extending to resolution limits of 1.9A and 2.7A, and to R factors of 17% and 18%, respectively. The inhibitor, N-(3-[(2-benzo[1,3]dioxol-5-yl-ethyl)[3-(1-methyl-3-oxo-1,3-dihydro-isoind ol-2-yl)-propionyl]-amino]-1-benzyl-2-(hydroxypropyl)-4-benzyloxy-3,5-dime thoxy-benzamide, belongs to a family of potent non-peptidic inhibitors that have large P1' groups. Such inhibitors could not be modeled into the binding cavity of the structure of plasmepsin II in complex with pepstatin A. Our structures reveal that the binding cavities of the new complex and uncomplexed plasmepsin II are considerably more open than that of the pepstatin A complex, allowing for larger heterocyclic groups in the P1', P2' and P2 positions. Both complexed and uncomplexed plasmepsin II crystallized in space group P2, with one monomer in the asymmetric unit. The structures show extensive interlocking of monomers around the crystallographic axis of symmetry, with areas in excess of 2300A(2) buried at the interface, and a loop of one monomer interacting with the binding cavity of the 2-fold related monomer. Electron density for this loop is only fully ordered in the complexed structure.

Novel uncomplexed and complexed structures of plasmepsin II, an aspartic protease from Plasmodium falciparum.,Asojo OA, Gulnik SV, Afonina E, Yu B, Ellman JA, Haque TS, Silva AM J Mol Biol. 2003 Mar 14;327(1):173-81. PMID:12614616^[4]

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

References

↑ Banerjee R, Liu J, Beatty W, Pelosof L, Klemba M, Goldberg DE. Four plasmepsins are active in the Plasmodium falciparum food vacuole, including a protease with an active-site histidine. Proc Natl Acad Sci U S A. 2002 Jan 22;99(2):990-5. doi: 10.1073/pnas.022630099., Epub 2002 Jan 8. PMID:11782538 doi:http://dx.doi.org/10.1073/pnas.022630099
↑ Istvan ES, Goldberg DE. Distal substrate interactions enhance plasmepsin activity. J Biol Chem. 2005 Feb 25;280(8):6890-6. doi: 10.1074/jbc.M412086200. Epub 2004, Dec 1. PMID:15574427 doi:http://dx.doi.org/10.1074/jbc.M412086200
↑ Luker KE, Francis SE, Gluzman IY, Goldberg DE. Kinetic analysis of plasmepsins I and II aspartic proteases of the Plasmodium falciparum digestive vacuole. Mol Biochem Parasitol. 1996 Jul;79(1):71-8. doi: 10.1016/0166-6851(96)02651-5. PMID:8844673 doi:http://dx.doi.org/10.1016/0166-6851(96)02651-5
↑ Asojo OA, Gulnik SV, Afonina E, Yu B, Ellman JA, Haque TS, Silva AM. Novel uncomplexed and complexed structures of plasmepsin II, an aspartic protease from Plasmodium falciparum. J Mol Biol. 2003 Mar 14;327(1):173-81. PMID:12614616

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/1lf4"

@@ Line 4: / Line 4: @@
 == Structural highlights ==
 <table><tr><td colspan='2'>[[1lf4]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Plasmodium_falciparum Plasmodium falciparum]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1LF4 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1LF4 FirstGlance]. <br>
-</td></tr><tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat"><div style='overflow: auto; max-height: 3em;'>[[1sme|1sme]], [[1lee|1lee]], [[1lf2|1lf2]], [[1lf3|1lf3]]</div></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]] 1.9&#8491;</td></tr>
-<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[https://en.wikipedia.org/wiki/Plasmepsin_II Plasmepsin II], with EC number [https://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.4.23.39 3.4.23.39] </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=1lf4 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1lf4 OCA], [https://pdbe.org/1lf4 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1lf4 RCSB], [https://www.ebi.ac.uk/pdbsum/1lf4 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1lf4 ProSAT]</span></td></tr>
 </table>
+== Function ==
+[https://www.uniprot.org/uniprot/PLM2_PLAFX PLM2_PLAFX] During the asexual blood stage, participates in initial cleavage of native host hemoglobin (Hb) resulting in Hb denaturation (PubMed:8844673, PubMed:11782538, PubMed:15574427). May cleave preferentially denatured hemoglobin that has been cleaved by PMI (PubMed:8844673). Digestion of host Hb is an essential step which provides the parasite with amino acids for protein synthesis, and regulates osmolarity (Probable).<ref>PMID:11782538</ref> <ref>PMID:15574427</ref> <ref>PMID:8844673</ref>
 == Evolutionary Conservation ==
 [[Image:Consurf_key_small.gif|200px|right]]
@@ Line 35: / Line 36: @@
 </StructureSection>
 [[Category: Large Structures]]
-[[Category: Plasmepsin II]]
 [[Category: Plasmodium falciparum]]
-[[Category: Afonina, E]]
+[[Category: Afonina E]]
-[[Category: Asojo, O A]]
+[[Category: Asojo OA]]
-[[Category: Ellman, J A]]
+[[Category: Ellman JA]]
-[[Category: Gulnik, S V]]
+[[Category: Gulnik SV]]
-[[Category: Haque, T S]]
+[[Category: Haque TS]]
-[[Category: Silva, A M]]
+[[Category: Silva AM]]
-[[Category: Yu, B]]
+[[Category: Yu B]]
-[[Category: Hydrolase]]

1lf4

From Proteopedia

Current revision

STRUCTURE OF PLASMEPSIN II

Structural highlights

Function

Evolutionary Conservation

Publication Abstract from PubMed

See Also

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

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