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| | <StructureSection load='6nxg' size='340' side='right'caption='[[6nxg]], [[Resolution|resolution]] 1.60Å' scene=''> | | <StructureSection load='6nxg' size='340' side='right'caption='[[6nxg]], [[Resolution|resolution]] 1.60Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[6nxg]] is a 3 chain structure with sequence from [http://en.wikipedia.org/wiki/Plavs Plavs]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6NXG OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6NXG FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[6nxg]] is a 3 chain structure with sequence from [https://en.wikipedia.org/wiki/Plasmodium_vivax_Sal-1 Plasmodium vivax Sal-1]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6NXG OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6NXG FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=BME:BETA-MERCAPTOETHANOL'>BME</scene>, <scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene>, <scene name='pdbligand=L7Y:5-(4-chlorophenyl)-3-({[3-(morpholine-4-carbonyl)phenyl]amino}methyl)pyridin-2(1H)-one'>L7Y</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene>, <scene name='pdbligand=MYA:TETRADECANOYL-COA'>MYA</scene>, <scene name='pdbligand=OXM:OXAMIC+ACID'>OXM</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]] 1.6Å</td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">PVX_085815 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=126793 PLAVS])</td></tr>
| + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=BME:BETA-MERCAPTOETHANOL'>BME</scene>, <scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene>, <scene name='pdbligand=L7Y:5-(4-chlorophenyl)-3-({[3-(morpholine-4-carbonyl)phenyl]amino}methyl)pyridin-2(1H)-one'>L7Y</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene>, <scene name='pdbligand=MYA:TETRADECANOYL-COA'>MYA</scene>, <scene name='pdbligand=OXM:OXAMIC+ACID'>OXM</scene></td></tr> |
| - | <tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Glycylpeptide_N-tetradecanoyltransferase Glycylpeptide N-tetradecanoyltransferase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.3.1.97 2.3.1.97] </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=6nxg FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6nxg OCA], [https://pdbe.org/6nxg PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6nxg RCSB], [https://www.ebi.ac.uk/pdbsum/6nxg PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6nxg 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=6nxg FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6nxg OCA], [http://pdbe.org/6nxg PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6nxg RCSB], [http://www.ebi.ac.uk/pdbsum/6nxg PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6nxg ProSAT]</span></td></tr> | + | |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/A5K1A2_PLAVS A5K1A2_PLAVS]] Adds a myristoyl group to the N-terminal glycine residue of certain cellular proteins (By similarity).[RuleBase:RU000586] | + | [https://www.uniprot.org/uniprot/A5K1A2_PLAVS A5K1A2_PLAVS] Adds a myristoyl group to the N-terminal glycine residue of certain cellular proteins (By similarity).[RuleBase:RU000586] |
| | <div style="background-color:#fffaf0;"> | | <div style="background-color:#fffaf0;"> |
| | == Publication Abstract from PubMed == | | == Publication Abstract from PubMed == |
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| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Glycylpeptide N-tetradecanoyltransferase]] | |
| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| - | [[Category: Plavs]] | + | [[Category: Plasmodium vivax Sal-1]] |
| - | [[Category: Mayclin, S]] | + | [[Category: Mayclin S]] |
| - | [[Category: Structural genomic]]
| + | [[Category: Staker BL]] |
| - | [[Category: Staker, B L]] | + | |
| - | [[Category: Ssgcid]]
| + | |
| - | [[Category: Transferase]]
| + | |
| - | [[Category: Transferase-transferase inhibitor complex]]
| + | |
| Structural highlights
6nxg is a 3 chain structure with sequence from Plasmodium vivax Sal-1. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
| | Method: | X-ray diffraction, Resolution 1.6Å |
| Ligands: | , , , , , , |
| Resources: | FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT |
Function
A5K1A2_PLAVS Adds a myristoyl group to the N-terminal glycine residue of certain cellular proteins (By similarity).[RuleBase:RU000586]
Publication Abstract from PubMed
New drugs that target Plasmodium species, the causative agents of malaria, are needed. The enzyme N-myristoyltransferase (NMT) is an essential protein which catalyzes the myristoylation of protein substrates, often to mediate membrane targeting. We screened ~1.8 million small molecules for activity against Plasmodium vivax NMT. Hits were triaged based on potency and physicochemical properties and further tested against P. vivax and P. falciparum NMTs. We assessed the activity of hits against human NMT1 and NMT2 and discarded compounds with low selectivity indices. We identified 23 chemical classes specific for the inhibition of Plasmodium NMTs over human NMTs, including multiple novel scaffolds. Co-crystallization of P. vivax NMT with one compound revealed peptide binding pocket binding. Other compounds show a range of potential modes of action. Our data provide insight into the activity of a collection of selective inhibitors of Plasmodium NMT and serve a starting point for subsequent medicinal chemistry efforts.
Identification of selective inhibitors of Plasmodium N-myristoyltransferase by high-throughput screening.,Harupa A, de Las Heras L, Colmenarejo G, Lyons-Abbott S, Reers A, Caballero Hernandez I, Chung CW, Charter D, Myler PJ, Fernandez-Menendez RM, Calderon F, Palomo S, Rodriguez B, Berlanga M, Herreros-Aviles E, Staker BL, Fernandez Alvaro E, Kaushansky A J Med Chem. 2019 Dec 18. doi: 10.1021/acs.jmedchem.9b01343. PMID:31850752[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Harupa A, de Las Heras L, Colmenarejo G, Lyons-Abbott S, Reers A, Caballero Hernandez I, Chung CW, Charter D, Myler PJ, Fernandez-Menendez RM, Calderon F, Palomo S, Rodriguez B, Berlanga M, Herreros-Aviles E, Staker BL, Fernandez Alvaro E, Kaushansky A. Identification of selective inhibitors of Plasmodium N-myristoyltransferase by high-throughput screening. J Med Chem. 2019 Dec 18. doi: 10.1021/acs.jmedchem.9b01343. PMID:31850752 doi:http://dx.doi.org/10.1021/acs.jmedchem.9b01343
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