6eu5: Difference between revisions
No edit summary |
No edit summary |
||
| Line 3: | Line 3: | ||
<StructureSection load='6eu5' size='340' side='right'caption='[[6eu5]], [[Resolution|resolution]] 1.50Å' scene=''> | <StructureSection load='6eu5' size='340' side='right'caption='[[6eu5]], [[Resolution|resolution]] 1.50Å' scene=''> | ||
== Structural highlights == | == Structural highlights == | ||
<table><tr><td colspan='2'>[[6eu5]] is a 1 chain structure with sequence from [ | <table><tr><td colspan='2'>[[6eu5]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Leima Leima]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6EU5 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6EU5 FirstGlance]. <br> | ||
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><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=MYA:TETRADECANOYL-COA'>MYA</scene></td></tr> | </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=MYA:TETRADECANOYL-COA'>MYA</scene></td></tr> | ||
<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[2wsa|2wsa]]</td></tr> | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat"><div style='overflow: auto; max-height: 3em;'>[[2wsa|2wsa]]</div></td></tr> | ||
<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">NMT, LMJF_32_0080 ([ | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">NMT, LMJF_32_0080 ([https://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=5664 LEIMA])</td></tr> | ||
<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[ | <tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[https://en.wikipedia.org/wiki/Glycylpeptide_N-tetradecanoyltransferase Glycylpeptide N-tetradecanoyltransferase], with EC number [https://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'>[ | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=6eu5 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6eu5 OCA], [https://pdbe.org/6eu5 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6eu5 RCSB], [https://www.ebi.ac.uk/pdbsum/6eu5 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6eu5 ProSAT]</span></td></tr> | ||
</table> | </table> | ||
== Function == | == Function == | ||
[[ | [[https://www.uniprot.org/uniprot/Q4Q5S8_LEIMA Q4Q5S8_LEIMA]] Adds a myristoyl group to the N-terminal glycine residue of certain cellular proteins (By similarity). | ||
<div style="background-color:#fffaf0;"> | <div style="background-color:#fffaf0;"> | ||
== Publication Abstract from PubMed == | == Publication Abstract from PubMed == | ||
Latest revision as of 13:20, 18 March 2021
Leishmania major N-myristoyltransferase with bound myristoyl-CoA and inhibitorLeishmania major N-myristoyltransferase with bound myristoyl-CoA and inhibitor
Structural highlights
Function[Q4Q5S8_LEIMA] Adds a myristoyl group to the N-terminal glycine residue of certain cellular proteins (By similarity). 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
|
| ||||||||||||||||||||||