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==CRYSTAL STRUCTURE OF LEISHMANIA MAJOR N-MYRISTOYLTRANSFERASE (NMT) WITH BOUND MYRISTOYL-COA AND A PYRAZOLE SULPHONAMIDE LIGAND== | ==CRYSTAL STRUCTURE OF LEISHMANIA MAJOR N-MYRISTOYLTRANSFERASE (NMT) WITH BOUND MYRISTOYL-COA AND A PYRAZOLE SULPHONAMIDE LIGAND== | ||
<StructureSection load='4a33' size='340' side='right' caption='[[4a33]], [[Resolution|resolution]] 2.40Å' scene=''> | <StructureSection load='4a33' size='340' side='right' caption='[[4a33]], [[Resolution|resolution]] 2.40Å' scene=''> | ||
== Structural highlights == | == Structural highlights == | ||
<table><tr><td colspan='2'>[[4a33]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/ | <table><tr><td colspan='2'>[[4a33]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Leima Leima]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4A33 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4A33 FirstGlance]. <br> | ||
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=MYA:TETRADECANOYL-COA'>MYA</scene>, <scene name='pdbligand=PS8:2,6-DICHLORO-4-(6-PIPERAZIN-1-YLPYRIDIN-3-YL)-N-(1,3,5-TRIMETHYL-1H-PYRAZOL-4-YL)BENZENESULFONAMIDE'>PS8</scene></td></tr> | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=MYA:TETRADECANOYL-COA'>MYA</scene>, <scene name='pdbligand=PS8:2,6-DICHLORO-4-(6-PIPERAZIN-1-YLPYRIDIN-3-YL)-N-(1,3,5-TRIMETHYL-1H-PYRAZOL-4-YL)BENZENESULFONAMIDE'>PS8</scene></td></tr> | ||
<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[4a32|4a32]], [[4a2z|4a2z]], [[4a30|4a30]], [[2wsa|2wsa]], [[4a31|4a31]]</td></tr> | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[4a32|4a32]], [[4a2z|4a2z]], [[4a30|4a30]], [[2wsa|2wsa]], [[4a31|4a31]]</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=4a33 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4a33 OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4a33 RCSB], [http://www.ebi.ac.uk/pdbsum/4a33 PDBsum]</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=4a33 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4a33 OCA], [http://pdbe.org/4a33 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4a33 RCSB], [http://www.ebi.ac.uk/pdbsum/4a33 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4a33 ProSAT]</span></td></tr> | ||
</table> | </table> | ||
== Function == | == Function == | ||
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From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | ||
</div> | </div> | ||
<div class="pdbe-citations 4a33" style="background-color:#fffaf0;"></div> | |||
== References == | == References == | ||
<references/> | <references/> | ||
| Line 23: | Line 25: | ||
</StructureSection> | </StructureSection> | ||
[[Category: Glycylpeptide N-tetradecanoyltransferase]] | [[Category: Glycylpeptide N-tetradecanoyltransferase]] | ||
[[Category: | [[Category: Leima]] | ||
[[Category: Brand, S]] | [[Category: Brand, S]] | ||
[[Category: Brenk, R]] | [[Category: Brenk, R]] | ||
Revision as of 19:16, 4 August 2016
CRYSTAL STRUCTURE OF LEISHMANIA MAJOR N-MYRISTOYLTRANSFERASE (NMT) WITH BOUND MYRISTOYL-COA AND A PYRAZOLE SULPHONAMIDE LIGANDCRYSTAL STRUCTURE OF LEISHMANIA MAJOR N-MYRISTOYLTRANSFERASE (NMT) WITH BOUND MYRISTOYL-COA AND A PYRAZOLE SULPHONAMIDE LIGAND
Structural highlights
Function[Q4Q5S8_LEIMA] Adds a myristoyl group to the N-terminal glycine residue of certain cellular proteins (By similarity). Publication Abstract from PubMedN-Myristoyltransferase (NMT) represents a promising drug target for human African trypanosomiasis (HAT), which is caused by the parasitic protozoa Trypanosoma brucei. We report the optimization of a high throughput screening hit (1) to give a lead molecule DDD85646 (63), which has potent activity against the enzyme (IC(50) = 2 nM) and T. brucei (EC(50) = 2 nM) in culture. The compound has good oral pharmacokinetics and cures rodent models of peripheral HAT infection. This compound provides an excellent tool for validation of T. brucei NMT as a drug target for HAT as well as a valuable lead for further optimization. Discovery of a novel class of orally active trypanocidal N-myristoyltransferase inhibitors.,Brand S, Cleghorn LA, McElroy SP, Robinson DA, Smith VC, Hallyburton I, Harrison JR, Norcross NR, Spinks D, Bayliss T, Norval S, Stojanovski L, Torrie LS, Frearson JA, Brenk R, Fairlamb AH, Ferguson MA, Read KD, Wyatt PG, Gilbert IH J Med Chem. 2012 Jan 12;55(1):140-52. Epub 2011 Dec 7. PMID:22148754[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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