4r6t: Difference between revisions
Jump to navigation
Jump to search
No edit summary |
No edit summary |
||
| Line 1: | Line 1: | ||
==Structure of the m17 leucyl aminopeptidase from malaria complexed with a hydroxamic acid-based inhibitor== | ==Structure of the m17 leucyl aminopeptidase from malaria complexed with a hydroxamic acid-based inhibitor== | ||
<StructureSection load='4r6t' size='340' side='right' caption='[[4r6t]], [[Resolution|resolution]] 2.60Å' scene=''> | <StructureSection load='4r6t' size='340' side='right'caption='[[4r6t]], [[Resolution|resolution]] 2.60Å' scene=''> | ||
== Structural highlights == | == Structural highlights == | ||
<table><tr><td colspan='2'>[[4r6t]] is a 12 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4R6T OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4R6T FirstGlance]. <br> | <table><tr><td colspan='2'>[[4r6t]] is a 12 chain structure with sequence from [http://en.wikipedia.org/wiki/Plaf7 Plaf7]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4R6T OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4R6T FirstGlance]. <br> | ||
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=1PE:PENTAETHYLENE+GLYCOL'>1PE</scene>, <scene name='pdbligand=CO3:CARBONATE+ION'>CO3</scene>, <scene name='pdbligand=DMS:DIMETHYL+SULFOXIDE'>DMS</scene>, <scene name='pdbligand=R5T:TERT-BUTYL+{(1S)-2-(HYDROXYAMINO)-2-OXO-1-[4-(1H-PYRAZOL-1-YL)PHENYL]ETHYL}CARBAMATE'>R5T</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr> | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=1PE:PENTAETHYLENE+GLYCOL'>1PE</scene>, <scene name='pdbligand=CO3:CARBONATE+ION'>CO3</scene>, <scene name='pdbligand=DMS:DIMETHYL+SULFOXIDE'>DMS</scene>, <scene name='pdbligand=R5T:TERT-BUTYL+{(1S)-2-(HYDROXYAMINO)-2-OXO-1-[4-(1H-PYRAZOL-1-YL)PHENYL]ETHYL}CARBAMATE'>R5T</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr> | ||
<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[3ebg|3ebg]], [[4r5v|4r5v]], [[4r5x|4r5x]], [[4r5t|4r5t]], [[4r76|4r76]], [[4r7m|4r7m]]</td></tr> | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[3ebg|3ebg]], [[4r5v|4r5v]], [[4r5x|4r5x]], [[4r5t|4r5t]], [[4r76|4r76]], [[4r7m|4r7m]]</td></tr> | ||
<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">LAP, PF14_0439 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=36329 PLAF7])</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=4r6t FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4r6t OCA], [http://pdbe.org/4r6t PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4r6t RCSB], [http://www.ebi.ac.uk/pdbsum/4r6t PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4r6t ProSAT]</span></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=4r6t FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4r6t OCA], [http://pdbe.org/4r6t PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4r6t RCSB], [http://www.ebi.ac.uk/pdbsum/4r6t PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4r6t ProSAT]</span></td></tr> | ||
</table> | </table> | ||
<div style="background-color:#fffaf0;"> | <div style="background-color:#fffaf0;"> | ||
== Publication Abstract from PubMed == | == Publication Abstract from PubMed == | ||
| Line 20: | Line 20: | ||
==See Also== | ==See Also== | ||
*[[Aminopeptidase|Aminopeptidase]] | *[[Aminopeptidase 3D structures|Aminopeptidase 3D structures]] | ||
== References == | == References == | ||
<references/> | <references/> | ||
__TOC__ | __TOC__ | ||
</StructureSection> | </StructureSection> | ||
[[Category: Large Structures]] | |||
[[Category: Plaf7]] | |||
[[Category: Drinkwater, N]] | [[Category: Drinkwater, N]] | ||
[[Category: Mcgowan, S]] | [[Category: Mcgowan, S]] | ||
[[Category: Hydrolase-hydrolase inhibitor complex]] | [[Category: Hydrolase-hydrolase inhibitor complex]] | ||
[[Category: Protease]] | [[Category: Protease]] | ||
Revision as of 13:00, 1 May 2019
Structure of the m17 leucyl aminopeptidase from malaria complexed with a hydroxamic acid-based inhibitorStructure of the m17 leucyl aminopeptidase from malaria complexed with a hydroxamic acid-based inhibitor
Structural highlights
Publication Abstract from PubMedPlasmodium parasites, the causative agents of malaria, have developed resistance to most of our current antimalarial therapies, including artemisinin combination therapies which are widely described as our last line of defense. Antimalarial agents with a novel mode of action are urgently required. Two Plasmodium falciparum aminopeptidases, PfA-M1 and PfA-M17, play crucial roles in the erythrocytic stage of infection and have been validated as potential antimalarial targets. Using compound-bound crystal structures of both enzymes, we have used a structure-guided approach to develop a novel series of inhibitors capable of potent inhibition of both PfA-M1 and PfA-M17 activity and parasite growth in culture. Herein we describe the design, synthesis, and evaluation of a series of hydroxamic acid-based inhibitors and demonstrate the compounds to be exciting new leads for the development of novel antimalarial therapeutics. Two-Pronged Attack: Dual Inhibition of Plasmodium falciparum M1 and M17 Metalloaminopeptidases by a Novel Series of Hydroxamic Acid-Based Inhibitors.,Mistry SN, Drinkwater N, Ruggeri C, Sivaraman KK, Loganathan S, Fletcher S, Drag M, Paiardini A, Avery VM, Scammells PJ, McGowan S J Med Chem. 2014 Oct 24. PMID:25299353[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
|
| ||||||||||||||||||||