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| | <StructureSection load='3qvc' size='340' side='right'caption='[[3qvc]], [[Resolution|resolution]] 2.10Å' scene=''> | | <StructureSection load='3qvc' size='340' side='right'caption='[[3qvc]], [[Resolution|resolution]] 2.10Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[3qvc]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Plafa Plafa]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3QVC OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3QVC FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[3qvc]] 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=3QVC OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3QVC FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</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]] 2.1Å</td></tr> |
| - | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat"><div style='overflow: auto; max-height: 3em;'>[[3qvi|3qvi]]</div></td></tr> | + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene></td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">hap ([https://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=5833 PLAFA])</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=3qvc FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3qvc OCA], [https://pdbe.org/3qvc PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3qvc RCSB], [https://www.ebi.ac.uk/pdbsum/3qvc PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3qvc 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=3qvc FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3qvc OCA], [https://pdbe.org/3qvc PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3qvc RCSB], [https://www.ebi.ac.uk/pdbsum/3qvc PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3qvc ProSAT]</span></td></tr> |
| | </table> | | </table> |
| | + | == Function == |
| | + | [https://www.uniprot.org/uniprot/PLM3_PLAFX PLM3_PLAFX] During the asexual blood stage, catalyzes the cleavage of denatured host hemoglobin (Hb) or globins (PubMed:11782538). 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> |
| | <div style="background-color:#fffaf0;"> | | <div style="background-color:#fffaf0;"> |
| | == Publication Abstract from PubMed == | | == Publication Abstract from PubMed == |
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| | </StructureSection> | | </StructureSection> |
| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| - | [[Category: Plafa]] | + | [[Category: Plasmodium falciparum]] |
| - | [[Category: Bhaumik, P]] | + | [[Category: Bhaumik P]] |
| - | [[Category: Gustchina, A]] | + | [[Category: Gustchina A]] |
| - | [[Category: Wlodawer, A]] | + | [[Category: Wlodawer A]] |
| - | [[Category: Aspartic protease]]
| + | |
| - | [[Category: Hap]]
| + | |
| - | [[Category: Histo-aspartic protease]]
| + | |
| - | [[Category: Hydrolase]]
| + | |
| - | [[Category: Malaria]]
| + | |
| - | [[Category: Plasmepsin]]
| + | |
| - | [[Category: Zymogen]]
| + | |
| Structural highlights
Function
PLM3_PLAFX During the asexual blood stage, catalyzes the cleavage of denatured host hemoglobin (Hb) or globins (PubMed:11782538). Digestion of host Hb is an essential step which provides the parasite with amino acids for protein synthesis, and regulates osmolarity (Probable).[1]
Publication Abstract from PubMed
Histo-aspartic protease (HAP) from Plasmodium falciparum is a promising target for the development of novel antimalarial drugs. The sequence of HAP is highly similar to those of pepsin-like aspartic proteases, but one of the two catalytic aspartates, Asp32, is replaced with histidine. Crystal structures of the truncated zymogen of HAP and of the complex of the mature enzyme with inhibitor KNI-10395 have been determined at 2.1 and 2.5 A resolution, respectively. As in other proplasmepsins, the propeptide of the zymogen interacts with the C-terminal domain of the enzyme, forcing the N- and C-terminal domains apart, thereby separating His32 and Asp215 and preventing formation of the mature active site. In the inhibitor complex, the enzyme forms a tight domain-swapped dimer, not previously seen in any aspartic proteases. The inhibitor is found in an unprecedented conformation resembling the letter U, stabilized by two intramolecular hydrogen bonds. Surprisingly, the location and conformation of the inhibitor are similar to those of the fragment of helix 2 comprising residues 34p-38p in the prosegments of the zymogens of gastric aspartic proteases; a corresponding helix assumes a vastly different orientation in proplasmepsins. Each inhibitor molecule is in contact with two molecules of HAP, interacting with the carboxylate group of the catalytic Asp215 of one HAP protomer through a water molecule, while also making a direct hydrogen bond to Glu278A' of the other protomer. A comparison of the shifts in the positions of the catalytic residues in the inhibitor complex presented here with those published previously gives further hints regarding the enzymatic mechanism of HAP.
Structural Insights into the Activation and Inhibition of Histo-Aspartic Protease from Plasmodium falciparum.,Bhaumik P, Xiao H, Hidaka K, Gustchina A, Kiso Y, Yada RY, Wlodawer A Biochemistry. 2011 Oct 18;50(41):8862-79. Epub 2011 Sep 26. PMID:21928835[2]
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
- ↑ Bhaumik P, Xiao H, Hidaka K, Gustchina A, Kiso Y, Yada RY, Wlodawer A. Structural Insights into the Activation and Inhibition of Histo-Aspartic Protease from Plasmodium falciparum. Biochemistry. 2011 Oct 18;50(41):8862-79. Epub 2011 Sep 26. PMID:21928835 doi:10.1021/bi201118z
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