6ee3: Difference between revisions

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 <StructureSection load='6ee3' size='340' side='right'caption='[[6ee3]], [[Resolution|resolution]] 1.82&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[6ee3]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Plafq Plafq]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6EE3 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6EE3 FirstGlance]. <br>
+<table><tr><td colspan='2'>[[6ee3]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Plasmodium_falciparum_FcB1/Columbia Plasmodium falciparum FcB1/Columbia]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6EE3 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6EE3 FirstGlance]. <br>
-</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=J4V:(1R,2r,3S,5R,7R)-N-[(1R)-2-(hydroxyamino)-2-oxo-1-(3,4,5-trifluoro[1,1-biphenyl]-4-yl)ethyl]tricyclo[3.3.1.1~3,7~]decane-2-carboxamide'>J4V</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene>, <scene name='pdbligand=PO4:PHOSPHATE+ION'>PO4</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</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]] 1.82&#8491;</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=6ee3 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6ee3 OCA], [http://pdbe.org/6ee3 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6ee3 RCSB], [http://www.ebi.ac.uk/pdbsum/6ee3 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6ee3 ProSAT]</span></td></tr>
+<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=J4V:(1R,2r,3S,5R,7R)-N-[(1R)-2-(hydroxyamino)-2-oxo-1-(3,4,5-trifluoro[1,1-biphenyl]-4-yl)ethyl]tricyclo[3.3.1.1~3,7~]decane-2-carboxamide'>J4V</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene>, <scene name='pdbligand=PO4:PHOSPHATE+ION'>PO4</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</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=6ee3 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6ee3 OCA], [https://pdbe.org/6ee3 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6ee3 RCSB], [https://www.ebi.ac.uk/pdbsum/6ee3 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6ee3 ProSAT]</span></td></tr>
 </table>
 == Function ==
-[[http://www.uniprot.org/uniprot/AMP1_PLAFQ AMP1_PLAFQ]] Displays aminopeptidase activity with a broad substrate specificity. Preferentially hydrolyzes L-Lys-AMC but also shows strong activity against L-Ala-AMC, L-Arg-AMC and L-Leu-AMC.<ref>PMID:12166515</ref> <ref>PMID:19196988</ref>
+[https://www.uniprot.org/uniprot/AMP1_PLAFQ AMP1_PLAFQ] Displays aminopeptidase activity with a broad substrate specificity. Preferentially hydrolyzes L-Lys-AMC but also shows strong activity against L-Ala-AMC, L-Arg-AMC and L-Leu-AMC.<ref>PMID:12166515</ref> <ref>PMID:19196988</ref>
-<div style="background-color:#fffaf0;">
-== Publication Abstract from PubMed ==
-There is an urgent clinical need for antimalarial compounds that target malaria caused by both Plasmodium falciparum and Plasmodium vivax. The M1 and M17 metalloexopeptidases play key roles in Plasmodium haemoglobin digestion, and are validated drug targets. We used a multi-target strategy to rationally design inhibitors capable of potent inhibition of the M1 and M17 aminopeptidases from both P. falciparum (Pf-M1 and Pf-M17) and P. vivax (Pv-M1 and Pv-M17). The novel chemical series contains a hydroxamic acid zinc binding group to coordinate catalytic zinc ion/s, and a variety of hydrophobic groups to probe the S1' pockets of the four target enzymes. Structural characterisation by co-crystallisation showed that selected compounds utilise new and unexpected binding modes; most notably, compounds substituted with bulky hydrophobic substituents displace the Pf-M17 catalytic zinc ion. Excitingly, key compounds of the series potently inhibit all four molecular targets and show antimalarial activity comparable to current clinical candidates.
-Hydroxamic acid inhibitors provide cross-species inhibition of Plasmodium M1 and M17 aminopeptidases.,Vinh NB, Drinkwater N, Malcolm TR, Kassiou M, Lucantoni L, Grin PM, Butler GS, Duffy S, Overall CM, Avery VM, Scammells PJ, McGowan S J Med Chem. 2018 Dec 11. doi: 10.1021/acs.jmedchem.8b01310. PMID:30537832<ref>PMID:30537832</ref>
-From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
-</div>
-<div class="pdbe-citations 6ee3" style="background-color:#fffaf0;"></div>
 ==See Also==
@@ Line 26: / Line 18: @@
 </StructureSection>
 [[Category: Large Structures]]
-[[Category: Plafq]]
+[[Category: Plasmodium falciparum FcB1/Columbia]]
-[[Category: Drinkwater, N]]
+[[Category: Drinkwater N]]
-[[Category: McGowan, S]]
+[[Category: McGowan S]]
-[[Category: Hydrolase]]
-[[Category: Hydrolase-hydrolase inhibitor complex]]
-[[Category: Hydroxamic acid]]
-[[Category: Inhibitor]]
-[[Category: M1 alanyl-aminopeptidase]]
-[[Category: Protease]]