6fz3: Difference between revisions
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<StructureSection load='6fz3' size='340' side='right'caption='[[6fz3]], [[Resolution|resolution]] 2.00Å' scene=''> | <StructureSection load='6fz3' size='340' side='right'caption='[[6fz3]], [[Resolution|resolution]] 2.00Å' scene=''> | ||
== Structural highlights == | == Structural highlights == | ||
<table><tr><td colspan='2'>[[6fz3]] is a 2 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6FZ3 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6FZ3 FirstGlance]. <br> | <table><tr><td colspan='2'>[[6fz3]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6FZ3 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6FZ3 FirstGlance]. <br> | ||
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=EBK:2,6-bis(chloranyl)-4-[2-(4-methylpiperazin-1-yl)pyridin-4-yl]-~{N}-(1,3,5-trimethylpyrazol-4-yl)benzenesulfonamide'>EBK</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene>, <scene name='pdbligand=MYA:TETRADECANOYL-COA'>MYA</scene></td></tr> | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=EBK:2,6-bis(chloranyl)-4-[2-(4-methylpiperazin-1-yl)pyridin-4-yl]-~{N}-(1,3,5-trimethylpyrazol-4-yl)benzenesulfonamide'>EBK</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene>, <scene name='pdbligand=MYA:TETRADECANOYL-COA'>MYA</scene></td></tr> | ||
<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[4c2z|4c2z]], [[3iu1|3iu1]], [[3iu2|3iu2]], [[3iwe|3iwe]], [[6fz2|6fz2]]</td></tr> | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[4c2z|4c2z]], [[3iu1|3iu1]], [[3iu2|3iu2]], [[3iwe|3iwe]], [[6fz2|6fz2]]</td></tr> | ||
<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">NMT1, NMT ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</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='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'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6fz3 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6fz3 OCA], [http://pdbe.org/6fz3 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6fz3 RCSB], [http://www.ebi.ac.uk/pdbsum/6fz3 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6fz3 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=6fz3 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6fz3 OCA], [http://pdbe.org/6fz3 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6fz3 RCSB], [http://www.ebi.ac.uk/pdbsum/6fz3 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6fz3 ProSAT]</span></td></tr> | ||
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== Function == | == Function == | ||
[[http://www.uniprot.org/uniprot/NMT1_HUMAN NMT1_HUMAN]] Adds a myristoyl group to the N-terminal glycine residue of certain cellular and viral proteins. | [[http://www.uniprot.org/uniprot/NMT1_HUMAN NMT1_HUMAN]] Adds a myristoyl group to the N-terminal glycine residue of certain cellular and viral proteins. | ||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
A model system of two related enzymes with conserved binding sites, namely N-myristoyltransferase from two different organisms, was studied to decipher the driving forces that lead to selective inhibition in such cases. Using a combination of computational and experimental tools, two different selectivity-determining features were identified. For some ligands, a change in side-chain flexibility appears to be responsible for selective inhibition. Remarkably, this was observed for residues orienting their side chains away from the ligands. For other ligands, selectivity is caused by interfering with a water molecule that binds more strongly to the off-target than to the target. On the basis of this finding, a virtual screen for selective compounds was conducted, resulting in three hit compounds with the desired selectivity profile. This study delivers a guideline on how to assess selectivity-determining features in proteins with conserved binding sites and to translate this knowledge into the design of selective inhibitors. | |||
How To Design Selective Ligands for Highly Conserved Binding Sites: A Case Study Using N-Myristoyltransferases as a Model System.,Kersten C, Fleischer E, Kehrein J, Borek C, Jaenicke E, Sotriffer C, Brenk R J Med Chem. 2019 Aug 19. doi: 10.1021/acs.jmedchem.9b00586. PMID:31423787<ref>PMID:31423787</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
</div> | |||
<div class="pdbe-citations 6fz3" style="background-color:#fffaf0;"></div> | |||
== References == | |||
<references/> | |||
__TOC__ | __TOC__ | ||
</StructureSection> | </StructureSection> | ||
[[Category: Glycylpeptide N-tetradecanoyltransferase]] | [[Category: Glycylpeptide N-tetradecanoyltransferase]] | ||
[[Category: Human]] | |||
[[Category: Large Structures]] | [[Category: Large Structures]] | ||
[[Category: Brenk, R]] | [[Category: Brenk, R]] | ||
Latest revision as of 18:54, 28 August 2019
Human N-myristoyltransferase (NMT1) with Myristoyl-CoA and inhibitor boundHuman N-myristoyltransferase (NMT1) with Myristoyl-CoA and inhibitor bound
Structural highlights
Function[NMT1_HUMAN] Adds a myristoyl group to the N-terminal glycine residue of certain cellular and viral proteins. Publication Abstract from PubMedA model system of two related enzymes with conserved binding sites, namely N-myristoyltransferase from two different organisms, was studied to decipher the driving forces that lead to selective inhibition in such cases. Using a combination of computational and experimental tools, two different selectivity-determining features were identified. For some ligands, a change in side-chain flexibility appears to be responsible for selective inhibition. Remarkably, this was observed for residues orienting their side chains away from the ligands. For other ligands, selectivity is caused by interfering with a water molecule that binds more strongly to the off-target than to the target. On the basis of this finding, a virtual screen for selective compounds was conducted, resulting in three hit compounds with the desired selectivity profile. This study delivers a guideline on how to assess selectivity-determining features in proteins with conserved binding sites and to translate this knowledge into the design of selective inhibitors. How To Design Selective Ligands for Highly Conserved Binding Sites: A Case Study Using N-Myristoyltransferases as a Model System.,Kersten C, Fleischer E, Kehrein J, Borek C, Jaenicke E, Sotriffer C, Brenk R J Med Chem. 2019 Aug 19. doi: 10.1021/acs.jmedchem.9b00586. PMID:31423787[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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