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6mb1

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<StructureSection load='6mb1' size='340' side='right'caption='[[6mb1]], [[Resolution|resolution]] 1.50&Aring;' scene=''>
<StructureSection load='6mb1' size='340' side='right'caption='[[6mb1]], [[Resolution|resolution]] 1.50&Aring;' scene=''>
== Structural highlights ==
== Structural highlights ==
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<table><tr><td colspan='2'>[[6mb1]] is a 3 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6MB1 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6MB1 FirstGlance]. <br>
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<table><tr><td colspan='2'>[[6mb1]] is a 3 chain structure with sequence from [https://en.wikipedia.org/wiki/Plasmodium_vivax Plasmodium vivax]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6MB1 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6MB1 FirstGlance]. <br>
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</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene>, <scene name='pdbligand=JCY:1-(5-{4-fluoro-2-[2-(1,3,5-trimethyl-1H-pyrazol-4-yl)ethoxy]phenyl}-1-methyl-1H-indazol-3-yl)-N,N-dimethylmethanamine'>JCY</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene>, <scene name='pdbligand=YNC:TETRADEC-13-YNOIC+ACID+-+COA+THIOESTER'>YNC</scene></td></tr>
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</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.5&#8491;</td></tr>
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<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>
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<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene>, <scene name='pdbligand=JCY:1-(5-{4-fluoro-2-[2-(1,3,5-trimethyl-1H-pyrazol-4-yl)ethoxy]phenyl}-1-methyl-1H-indazol-3-yl)-N,N-dimethylmethanamine'>JCY</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene>, <scene name='pdbligand=YNC:TETRADEC-13-YNOIC+ACID+-+COA+THIOESTER'>YNC</scene></td></tr>
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<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=6mb1 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6mb1 OCA], [http://pdbe.org/6mb1 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6mb1 RCSB], [http://www.ebi.ac.uk/pdbsum/6mb1 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6mb1 ProSAT]</span></td></tr>
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<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=6mb1 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6mb1 OCA], [https://pdbe.org/6mb1 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6mb1 RCSB], [https://www.ebi.ac.uk/pdbsum/6mb1 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6mb1 ProSAT]</span></td></tr>
</table>
</table>
== Function ==
== Function ==
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[[http://www.uniprot.org/uniprot/A0A1G4HIY1_PLAVI A0A1G4HIY1_PLAVI]] Adds a myristoyl group to the N-terminal glycine residue of certain cellular proteins.[RuleBase:RU000586]
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[https://www.uniprot.org/uniprot/A0A1G4HIY1_PLAVI A0A1G4HIY1_PLAVI] Adds a myristoyl group to the N-terminal glycine residue of certain cellular proteins.[RuleBase:RU000586]
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<div style="background-color:#fffaf0;">
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== Publication Abstract from PubMed ==
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The attachment of myristate to the N-terminal glycine of certain proteins is largely a co-translational modification catalyzed by N-myristoyltransferase (NMT), and involved in protein membrane-localization. Pathogen NMT is a validated therapeutic target in numerous infectious diseases including malaria. In Plasmodium falciparum, NMT substrates are important in essential processes including parasite gliding motility and host cell invasion. Here, we generated parasites resistant to a particular NMT inhibitor series and show that resistance in an in vitro parasite growth assay is mediated by a single amino acid substitution in the NMT substrate-binding pocket. The basis of resistance was validated and analyzed with a structure-guided approach using crystallography, in combination with enzyme activity, stability, and surface plasmon resonance assays, allowing identification of another inhibitor series unaffected by this substitution. We suggest that resistance studies incorporated early in the drug development process help selection of drug combinations to impede rapid evolution of parasite resistance.
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Structure-Guided Identification of Resistance Breaking Antimalarial NMyristoyltransferase Inhibitors.,Schlott AC, Mayclin S, Reers AR, Coburn-Flynn O, Bell AS, Green J, Knuepfer E, Charter D, Bonnert R, Campo B, Burrows J, Lyons-Abbott S, Staker BL, Chung CW, Myler PJ, Fidock DA, Tate EW, Holder AA Cell Chem Biol. 2019 Apr 9. pii: S2451-9456(19)30111-4. doi:, 10.1016/j.chembiol.2019.03.015. PMID:31080074<ref>PMID:31080074</ref>
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From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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</div>
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<div class="pdbe-citations 6mb1" style="background-color:#fffaf0;"></div>
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== References ==
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<references/>
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__TOC__
__TOC__
</StructureSection>
</StructureSection>
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[[Category: Glycylpeptide N-tetradecanoyltransferase]]
 
[[Category: Large Structures]]
[[Category: Large Structures]]
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[[Category: Plasmodium vivax]]
[[Category: Structural genomic]]
[[Category: Structural genomic]]
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[[Category: Glycylpeptide n-tetradecanoyltransferase]]
 
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[[Category: N-myristoyltransferase]]
 
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[[Category: Nmt]]
 
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[[Category: Ssgcid]]
 
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[[Category: Transferase]]
 

Current revision

Crystal structure of N-myristoyl transferase (NMT) from Plasmodium vivax in complex with inhibitor IMP-1002

PDB ID 6mb1

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