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| | ==Structure of proplasmepsin II from Plasmodium falciparum, Space Group P43212== | | ==Structure of proplasmepsin II from Plasmodium falciparum, Space Group P43212== |
| - | <StructureSection load='5bwy' size='340' side='right' caption='[[5bwy]], [[Resolution|resolution]] 2.64Å' scene=''> | + | <StructureSection load='5bwy' size='340' side='right'caption='[[5bwy]], [[Resolution|resolution]] 2.64Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[5bwy]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Plafa Plafa]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5BWY OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5BWY FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[5bwy]] 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=5BWY OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5BWY FirstGlance]. <br> |
| - | </td></tr><tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">PFAG_05140 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=5833 PLAFA])</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]] 2.644Å</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=5bwy FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5bwy OCA], [http://pdbe.org/5bwy PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5bwy RCSB], [http://www.ebi.ac.uk/pdbsum/5bwy PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5bwy ProSAT]</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=5bwy FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5bwy OCA], [https://pdbe.org/5bwy PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5bwy RCSB], [https://www.ebi.ac.uk/pdbsum/5bwy PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5bwy ProSAT]</span></td></tr> |
| | </table> | | </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:11782538, PubMed:15574427, PubMed:8844673). 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> |
| | <div style="background-color:#fffaf0;"> | | <div style="background-color:#fffaf0;"> |
| | == Publication Abstract from PubMed == | | == Publication Abstract from PubMed == |
| - | The malarial aspartic proteinases (plasmepsins) have been discovered in several species of Plasmodium, including all four of the human malarial pathogens. In P.falciparum, plasmepsins I, II, IV and HAP have been directly implicated in hemoglobin degradation during malaria infection, and are now considered targets for anti-malarial drug design. The plasmepsins are produced from inactive zymogens, proplasmepsins, having unusually long N-terminal prosegments of more than 120 amino acids. Structural and biochemical evidence suggests that the conversion process of proplasmepsins to plasmepsins differs substantially from the gastric and plant aspartic proteinases. Instead of blocking substrate access to a pre-formed active site, the prosegment enforces a conformation in which proplasmepsin cannot form a functional active site. We have determined crystal structures of plasmepsin and proplasmepsin from P.vivax. The three-dimensional structure of P.vivax plasmepsin is typical of the monomeric aspartic proteinases, and the structure of P.vivax proplasmepsin is similar to that of P.falciparum proplasmepsin II. A dramatic refolding of the mature N terminus and a large (18 degrees ) reorientation of the N-domain between P.vivax proplasmepsin and plasmepsin results in a severe distortion of the active site region of the zymogen relative to that of the mature enzyme. The present structures confirm that the mode of inactivation observed originally in P.falciparum proplasmepsin II, i.e. an incompletely formed active site, is a true structural feature and likely represents the general mode of inactivation of the related proplasmepsins.
| + | Plasmepsin IV from Plasmodium falciparum (PM IV) is a promising target for the development of novel antimalarial drugs. Here, the crystal structure of the truncated zymogen of PM IV (pPM IV), consisting of the mature enzyme plus a prosegment of 47 residues, has been determined at 1.5 A resolution. pPM IV presents the fold previously described for studied proplasmepsins, displaying closer similarities to proplasmepin IV from P. vivax (pPvPM) than to the other two proplasmepsins from P. falciparum. The study and comparison of the pPM IV structure with the proplasmepsin structures described previously provide information about the similarities and differences in the inactivation-activation mechanisms among the plasmepsin zymogens. |
| | | | |
| - | Structural insights into the activation of P. vivax plasmepsin.,Bernstein NK, Cherney MM, Yowell CA, Dame JB, James MN J Mol Biol. 2003 Jun 6;329(3):505-24. PMID:12767832<ref>PMID:12767832</ref>
| + | Crystal structure of Plasmodium falciparum proplasmepsin IV: the plasticity of proplasmepsins.,Recacha R, Jaudzems K, Akopjana I, Jirgensons A, Tars K Acta Crystallogr F Struct Biol Commun. 2016 Sep;72(Pt 9):659-66. doi:, 10.1107/S2053230X16011663. Epub 2016 Aug 9. PMID:27599854<ref>PMID:27599854</ref> |
| | | | |
| | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> |
| | </div> | | </div> |
| | <div class="pdbe-citations 5bwy" style="background-color:#fffaf0;"></div> | | <div class="pdbe-citations 5bwy" style="background-color:#fffaf0;"></div> |
| | + | |
| | + | ==See Also== |
| | + | *[[Plasmepsin|Plasmepsin]] |
| | == References == | | == References == |
| | <references/> | | <references/> |
| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Plafa]] | + | [[Category: Large Structures]] |
| - | [[Category: Akopjana, I]] | + | [[Category: Plasmodium falciparum]] |
| - | [[Category: Jaudzems, K]] | + | [[Category: Akopjana I]] |
| - | [[Category: Recacha, R]] | + | [[Category: Jaudzems K]] |
| - | [[Category: Tars, K]] | + | [[Category: Recacha R]] |
| - | [[Category: Hydrolase]]
| + | [[Category: Tars K]] |
| - | [[Category: Malaria]]
| + | |
| Structural highlights
Function
PLM2_PLAFX During the asexual blood stage, participates in initial cleavage of native host hemoglobin (Hb) resulting in Hb denaturation (PubMed:11782538, PubMed:15574427, PubMed:8844673). 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]
Publication Abstract from PubMed
Plasmepsin IV from Plasmodium falciparum (PM IV) is a promising target for the development of novel antimalarial drugs. Here, the crystal structure of the truncated zymogen of PM IV (pPM IV), consisting of the mature enzyme plus a prosegment of 47 residues, has been determined at 1.5 A resolution. pPM IV presents the fold previously described for studied proplasmepsins, displaying closer similarities to proplasmepin IV from P. vivax (pPvPM) than to the other two proplasmepsins from P. falciparum. The study and comparison of the pPM IV structure with the proplasmepsin structures described previously provide information about the similarities and differences in the inactivation-activation mechanisms among the plasmepsin zymogens.
Crystal structure of Plasmodium falciparum proplasmepsin IV: the plasticity of proplasmepsins.,Recacha R, Jaudzems K, Akopjana I, Jirgensons A, Tars K Acta Crystallogr F Struct Biol Commun. 2016 Sep;72(Pt 9):659-66. doi:, 10.1107/S2053230X16011663. Epub 2016 Aug 9. PMID:27599854[4]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
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
- ↑ Recacha R, Jaudzems K, Akopjana I, Jirgensons A, Tars K. Crystal structure of Plasmodium falciparum proplasmepsin IV: the plasticity of proplasmepsins. Acta Crystallogr F Struct Biol Commun. 2016 Sep;72(Pt 9):659-66. doi:, 10.1107/S2053230X16011663. Epub 2016 Aug 9. PMID:27599854 doi:http://dx.doi.org/10.1107/S2053230X16011663
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