2r9b: Difference between revisions
New page: left|200px<br /><applet load="2r9b" size="350" color="white" frame="true" align="right" spinBox="true" caption="2r9b, resolution 2.800Å" /> '''Structural Analysis... |
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== | ==Structural Analysis of Plasmepsin 2 from Plasmodium falciparum complexed with a peptide-based inhibitor== | ||
<StructureSection load='2r9b' size='340' side='right'caption='[[2r9b]], [[Resolution|resolution]] 2.80Å' scene=''> | |||
== Structural highlights == | |||
[ | <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='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='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='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> | |||
[[ | == 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]] | ||
Check<jmol> | |||
<jmolCheckbox> | |||
<scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/r9/2r9b_consurf.spt"</scriptWhenChecked> | |||
<scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked> | |||
<text>to colour the structure by Evolutionary Conservation</text> | |||
</jmolCheckbox> | |||
</jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/main_output.php?pdb_ID=2r9b ConSurf]. | |||
<div style="clear:both"></div> | |||
<div style="background-color:#fffaf0;"> | |||
== 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<ref>PMID:19271776</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
</div> | |||
<div class="pdbe-citations 2r9b" style="background-color:#fffaf0;"></div> | |||
==See Also== | |||
*[[Plasmepsin|Plasmepsin]] | |||
== References == | |||
<references/> | |||
__TOC__ | |||
</StructureSection> | |||
[[Category: Large Structures]] | |||
[[Category: Plasmodium falciparum 3D7]] | |||
[[Category: Dunn BM]] | |||
[[Category: Liu P]] | |||
[[Category: Marzahn MR]] | |||
[[Category: McKenna R]] | |||
[[Category: Robbins AH]] | |||
