4cae

From Proteopedia

(Difference between revisions)
Jump to: navigation, search
Line 3: Line 3:
<StructureSection load='4cae' size='340' side='right'caption='[[4cae]], [[Resolution|resolution]] 1.46&Aring;' scene=''>
<StructureSection load='4cae' size='340' side='right'caption='[[4cae]], [[Resolution|resolution]] 1.46&Aring;' scene=''>
== Structural highlights ==
== Structural highlights ==
-
<table><tr><td colspan='2'>[[4cae]] is a 3 chain structure with sequence from [http://en.wikipedia.org/wiki/Haemamoeba_vivax Haemamoeba vivax]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4CAE OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4CAE FirstGlance]. <br>
+
<table><tr><td colspan='2'>[[4cae]] 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=4CAE OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4CAE FirstGlance]. <br>
-
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=3F3:4-[(2-{5-[(3-METHOXYPHENYL)METHYL]-1,3,4-OXADIAZOL-2-YL}-1-BENZOTHIOPHEN-3-YL)OXY]PIPERIDINE'>3F3</scene>, <scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=DMS:DIMETHYL+SULFOXIDE'>DMS</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene>, <scene name='pdbligand=NHW:2-OXOPENTADECYL-COA'>NHW</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></td></tr>
+
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=3F3:4-[(2-{5-[(3-METHOXYPHENYL)METHYL]-1,3,4-OXADIAZOL-2-YL}-1-BENZOTHIOPHEN-3-YL)OXY]PIPERIDINE'>3F3</scene>, <scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=DMS:DIMETHYL+SULFOXIDE'>DMS</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene>, <scene name='pdbligand=NHW:2-OXOPENTADECYL-COA'>NHW</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></td></tr>
-
<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[4caf|4caf]]</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=4cae FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4cae OCA], [https://pdbe.org/4cae PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4cae RCSB], [https://www.ebi.ac.uk/pdbsum/4cae PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4cae ProSAT]</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=4cae FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4cae OCA], [http://pdbe.org/4cae PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4cae RCSB], [http://www.ebi.ac.uk/pdbsum/4cae PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4cae 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;">
+
-
== Publication Abstract from PubMed ==
+
-
N-Myristoyltransferase (NMT) is an essential eukaryotic enzyme and an attractive drug target in parasitic infections such as malaria. We have previously reported that 2-(3-(piperidin-4-yloxy)benzo[b]thiophen-2-yl)-5-((1,3,5-trimethyl-1H-pyrazol-4-y l)methyl)-1,3,4-oxadiazole (34c) is a high affinity inhibitor of both Plasmodium falciparum and P. vivax NMT and displays activity in vivo against a rodent malaria model. Here we describe the discovery of 34c through optimization of a previously described series. Development, guided by targeting a ligand efficiency dependent lipophilicity (LELP) score of less than 10, yielded a 100-fold increase in enzyme affinity and a 100-fold drop in lipophilicity with the addition of only two heavy atoms. 34c was found to be equipotent on chloroquine-sensitive and -resistant cell lines and on both blood and liver stage forms of the parasite. These data further validate NMT as an exciting drug target in malaria and support 34c as an attractive tool for further optimization.
+
-
 
+
-
Design and Synthesis of High Affinity Inhibitors of Plasmodium falciparum and Plasmodium vivax N-Myristoyltransferases Directed by Ligand Efficiency Dependent Lipophilicity (LELP).,Rackham MD, Brannigan JA, Rangachari K, Meister S, Wilkinson AJ, Holder AA, Leatherbarrow RJ, Tate EW J Med Chem. 2014 Mar 27;57(6):2773-88. doi: 10.1021/jm500066b. Epub 2014 Mar 18. PMID:24641010<ref>PMID:24641010</ref>
+
-
 
+
-
From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
+
-
</div>
+
-
<div class="pdbe-citations 4cae" style="background-color:#fffaf0;"></div>
+
-
== References ==
+
-
<references/>
+
__TOC__
__TOC__
</StructureSection>
</StructureSection>
-
[[Category: Glycylpeptide N-tetradecanoyltransferase]]
 
-
[[Category: Haemamoeba vivax]]
 
[[Category: Large Structures]]
[[Category: Large Structures]]
-
[[Category: Brannigan, J A]]
+
[[Category: Plasmodium vivax]]
-
[[Category: Holder, A A]]
+
[[Category: Brannigan JA]]
-
[[Category: Leatherbarrow, R J]]
+
[[Category: Holder AA]]
-
[[Category: Rackham, M D]]
+
[[Category: Leatherbarrow RJ]]
-
[[Category: Rangachari, K]]
+
[[Category: Rackham MD]]
-
[[Category: Tate, E W]]
+
[[Category: Rangachari K]]
-
[[Category: Wilkinson, A J]]
+
[[Category: Tate EW]]
-
[[Category: Benzothiophene]]
+
[[Category: Wilkinson AJ]]
-
[[Category: Inhibitor]]
+
-
[[Category: Malaria]]
+
-
[[Category: Myristoylation]]
+
-
[[Category: Transferase]]
+

Revision as of 17:34, 7 September 2022

Plasmodium vivax N-myristoyltransferase in complex with a benzothiophene inhibitor (compound 20b)

PDB ID 4cae

Drag the structure with the mouse to rotate

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/4cae"
Personal tools