3qvi

From Proteopedia

(Difference between revisions)

Current revision

Crystal structure of KNI-10395 bound histo-aspartic protease (HAP) from Plasmodium falciparum

Structural highlights

3qvi is a 4 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 2.5Å
Ligands:	, , , , ,
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

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.

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

1 Structural highlights
2 Function
3 Publication Abstract from PubMed
4 See Also
5 References

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/3qvi"

Categories: Large Structures | Plasmodium falciparum | Bhaumik P | Gustchina A | Wlodawer A

@@ Line 3: / Line 3: @@
 <StructureSection load='3qvi' size='340' side='right'caption='[[3qvi]], [[Resolution|resolution]] 2.50&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[3qvi]] is a 4 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=3QVI OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3QVI FirstGlance]. <br>
+<table><tr><td colspan='2'>[[3qvi]] is a 4 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=3QVI OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3QVI FirstGlance]. <br>
-</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=ACT:ACETATE+ION'>ACT</scene>, <scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene>, <scene name='pdbligand=K95:(4R)-N-[(1S,2R)-2-HYDROXY-2,3-DIHYDRO-1H-INDEN-1-YL]-3-[(2S,3S)-2-HYDROXY-3-{[S-METHYL-N-(PHENYLACETYL)-L-CYSTEINYL]AMINO}-4-PHENYLBUTANOYL]-5,5-DIMETHYL-1,3-THIAZOLIDINE-4-CARBOXAMIDE'>K95</scene>, <scene name='pdbligand=NA:SODIUM+ION'>NA</scene>, <scene name='pdbligand=PG4:TETRAETHYLENE+GLYCOL'>PG4</scene>, <scene name='pdbligand=PG5:1-METHOXY-2-[2-(2-METHOXY-ETHOXY]-ETHANE'>PG5</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]] 2.5&#8491;</td></tr>
-<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat"><div style='overflow: auto; max-height: 3em;'>[[3qvc|3qvc]]</div></td></tr>
+<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=ACT:ACETATE+ION'>ACT</scene>, <scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene>, <scene name='pdbligand=K95:(4R)-N-[(1S,2R)-2-HYDROXY-2,3-DIHYDRO-1H-INDEN-1-YL]-3-[(2S,3S)-2-HYDROXY-3-{[S-METHYL-N-(PHENYLACETYL)-L-CYSTEINYL]AMINO}-4-PHENYLBUTANOYL]-5,5-DIMETHYL-1,3-THIAZOLIDINE-4-CARBOXAMIDE'>K95</scene>, <scene name='pdbligand=NA:SODIUM+ION'>NA</scene>, <scene name='pdbligand=PG4:TETRAETHYLENE+GLYCOL'>PG4</scene>, <scene name='pdbligand=PG5:1-METHOXY-2-[2-(2-METHOXY-ETHOXY]-ETHANE'>PG5</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=3qvi FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3qvi OCA], [https://pdbe.org/3qvi PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3qvi RCSB], [https://www.ebi.ac.uk/pdbsum/3qvi PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3qvi ProSAT]</span></td></tr>
 </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;">
 == Publication Abstract from PubMed ==
@@ Line 26: / Line 27: @@
 </StructureSection>
 [[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-hydrolase inhibitor complex]]
-[[Category: Kni]]
-[[Category: Kni-10395]]
-[[Category: Malaria]]
-[[Category: Plasmepsin]]

3qvi

From Proteopedia

Current revision

Crystal structure of KNI-10395 bound histo-aspartic protease (HAP) from Plasmodium falciparum

Structural highlights

Function

Publication Abstract from PubMed

See Also

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

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