5uut
From Proteopedia
(Difference between revisions)
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<StructureSection load='5uut' size='340' side='right' caption='[[5uut]], [[Resolution|resolution]] 2.25Å' scene=''> | <StructureSection load='5uut' size='340' side='right' caption='[[5uut]], [[Resolution|resolution]] 2.25Å' scene=''> | ||
== Structural highlights == | == Structural highlights == | ||
| - | <table><tr><td colspan='2'>[[5uut]] is a 2 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5UUT OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5UUT FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[5uut]] 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=5UUT OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5UUT FirstGlance]. <br> |
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=CIT:CITRIC+ACID'>CIT</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=CIT:CITRIC+ACID'>CIT</scene>, <scene name='pdbligand=MYA:TETRADECANOYL-COA'>MYA</scene></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=5uut FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5uut OCA], [http://pdbe.org/5uut PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5uut RCSB], [http://www.ebi.ac.uk/pdbsum/5uut PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5uut 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=5uut FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5uut OCA], [http://pdbe.org/5uut PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5uut RCSB], [http://www.ebi.ac.uk/pdbsum/5uut PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5uut 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 == | ||
| + | Protein N-myristoylation enables localization to membranes and helps maintain protein conformation and function. N-myristoyltransferases (NMT) catalyze co- or posttranslational myristoylation of Src family kinases and other oncogenic proteins, thereby regulating their function. In this study, we provide genetic and pharmacologic evidence that inhibiting the N-myristoyltransferase NMT1 suppresses cell-cycle progression, proliferation, and malignant growth of prostate cancer cells. Loss of myristoylation abolished the tumorigenic potential of Src and its synergy with androgen receptor in mediating tumor invasion. We identified the myristoyl-CoA analogue B13 as a small-molecule inhibitor of NMT1 enzymatic activity. B13 exposure blocked Src myristoylation and Src localization to the cytoplasmic membrane, attenuating Src-mediated oncogenic signaling. B13 exerted its anti-invasive and antitumor effects against prostate cancer cells, with minimal toxic side-effects in vivo Structural optimization based on structure-activity relationships enabled the chemical synthesis of LCL204, with enhanced inhibitory potency against NMT1. Collectively, our results offer a preclinical proof of concept for the use of protein myristoylation inhibitors as a strategy to block prostate cancer progression. Cancer Res; 77(24); 6950-62. (c)2017 AACR. | ||
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| + | Blocking Myristoylation of Src Inhibits Its Kinase Activity and Suppresses Prostate Cancer Progression.,Kim S, Alsaidan OA, Goodwin O, Li Q, Sulejmani E, Han Z, Bai A, Albers T, Beharry Z, Zheng YG, Norris JS, Szulc ZM, Bielawska A, Lebedyeva I, Pegan SD, Cai H Cancer Res. 2017 Dec 15;77(24):6950-6962. doi: 10.1158/0008-5472.CAN-17-0981., Epub 2017 Oct 16. PMID:29038344<ref>PMID:29038344</ref> | ||
| + | |||
| + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | ||
| + | </div> | ||
| + | <div class="pdbe-citations 5uut" style="background-color:#fffaf0;"></div> | ||
| + | == References == | ||
| + | <references/> | ||
__TOC__ | __TOC__ | ||
</StructureSection> | </StructureSection> | ||
[[Category: Glycylpeptide N-tetradecanoyltransferase]] | [[Category: Glycylpeptide N-tetradecanoyltransferase]] | ||
| + | [[Category: Human]] | ||
[[Category: Goodwin, O]] | [[Category: Goodwin, O]] | ||
[[Category: Pegan, S]] | [[Category: Pegan, S]] | ||
Revision as of 09:21, 30 January 2019
N-myristoyltransferase 1 (NMT) bound to myristoyl-CoA
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