View source for 6fz5


==Human N-myristoyltransferase (NMT1) with Myristoyl-CoA and inhibitor bound==
<StructureSection load='6fz5' size='340' side='right'caption='[[6fz5]], [[Resolution|resolution]] 1.89&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[6fz5]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6FZ5 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6FZ5 FirstGlance]. <br>
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.89&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=BXN:4-[3-[(8~{a}~{R})-3,4,6,7,8,8~{a}-hexahydro-1~{H}-pyrrolo[1,2-a]pyrazin-2-yl]propyl]-2,6-bis(chloranyl)-~{N}-methyl-~{N}-(1,3,5-trimethylpyrazol-4-yl)benzenesulfonamide'>BXN</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='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=6fz5 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6fz5 OCA], [https://pdbe.org/6fz5 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6fz5 RCSB], [https://www.ebi.ac.uk/pdbsum/6fz5 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6fz5 ProSAT]</span></td></tr>
</table>
== Function ==
[https://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&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 6fz5" style="background-color:#fffaf0;"></div>
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Brenk R]]
[[Category: Kersten FC]]