|
|
| Line 3: |
Line 3: |
| | <StructureSection load='2r9b' size='340' side='right'caption='[[2r9b]], [[Resolution|resolution]] 2.80Å' scene=''> | | <StructureSection load='2r9b' size='340' side='right'caption='[[2r9b]], [[Resolution|resolution]] 2.80Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[2r9b]] is a 4 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=2R9B OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2R9B FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[2r9b]] is a 4 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=2R9B OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2R9B FirstGlance]. <br> |
| - | </td></tr><tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=DCL:2-AMINO-4-METHYL-PENTAN-1-OL'>DCL</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]] 2.8Å</td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">plasmepsin 2 ([https://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=36329 PLAF7])</td></tr>
| + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=DCL:2-AMINO-4-METHYL-PENTAN-1-OL'>DCL</scene></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=2r9b FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2r9b OCA], [https://pdbe.org/2r9b PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2r9b RCSB], [https://www.ebi.ac.uk/pdbsum/2r9b PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2r9b 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=2r9b FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2r9b OCA], [https://pdbe.org/2r9b PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2r9b RCSB], [https://www.ebi.ac.uk/pdbsum/2r9b PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2r9b 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: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 == | | == Evolutionary Conservation == |
| | [[Image:Consurf_key_small.gif|200px|right]] | | [[Image:Consurf_key_small.gif|200px|right]] |
| Line 36: |
Line 37: |
| | </StructureSection> | | </StructureSection> |
| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| - | [[Category: Plaf7]] | + | [[Category: Plasmodium falciparum 3D7]] |
| - | [[Category: Plasmepsin II]]
| + | [[Category: Dunn BM]] |
| - | [[Category: Dunn, B M]] | + | [[Category: Liu P]] |
| - | [[Category: Liu, P]] | + | [[Category: Marzahn MR]] |
| - | [[Category: Marzahn, M R]] | + | [[Category: McKenna R]] |
| - | [[Category: McKenna, R]] | + | [[Category: Robbins AH]] |
| - | [[Category: Robbins, A H]] | + | |
| - | [[Category: Beta fold aspartyl protease]]
| + | |
| - | [[Category: Glycoprotein]]
| + | |
| - | [[Category: Hydrolase-hydrolase inhibitor complex]]
| + | |
| - | [[Category: Vacuole]]
| + | |
| - | [[Category: Zymogen]]
| + | |
| Structural highlights
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
A mutated form of truncated proplasmepsin 1 (proPfPM1) from the human malaria parasite Plasmodium falciparum, proPfPM1 K110pN, was generated and overexpressed in Escherichia coli. The automaturation process was carried out at pH 4.0 and 4.5, and the optimal catalytic pH of the resulting mature PfPM1 was determined to be pH 5.5. This mature PfPM1 showed comparable binding affinity to peptide substrates and inhibitors with the naturally occurring form isolated from parasites. The S3-S3' subsite preferences of the recombinant mature PfPM1 were explored using combinatorial chemistry based peptide libraries. On the basis of the results, a peptidomimetic inhibitor (compound 1) was designed and yielded 5-fold selectivity for binding to PfPM1 versus the homologous human cathepsin D (hcatD). The 2.8 A structure of the PfPM2-compound 1 complex is reported. Modeling studies were conducted using a series of peptidomimetic inhibitors (compounds 1-6, Table 3) and three plasmepsins: the crystal structure of PfPM2, and homology derived models of PfPM1 and PfPM4.
Recombinant plasmepsin 1 from the human malaria parasite plasmodium falciparum: enzymatic characterization, active site inhibitor design, and structural analysis.,Liu P, Marzahn MR, Robbins AH, Gutierrez-de-Teran H, Rodriguez D, McClung SH, Stevens SM Jr, Yowell CA, Dame JB, McKenna R, Dunn BM Biochemistry. 2009 May 19;48(19):4086-99. PMID:19271776[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
- ↑ Liu P, Marzahn MR, Robbins AH, Gutierrez-de-Teran H, Rodriguez D, McClung SH, Stevens SM Jr, Yowell CA, Dame JB, McKenna R, Dunn BM. Recombinant plasmepsin 1 from the human malaria parasite plasmodium falciparum: enzymatic characterization, active site inhibitor design, and structural analysis. Biochemistry. 2009 May 19;48(19):4086-99. PMID:19271776 doi:10.1021/bi802059r
|
