4a31: Difference between revisions
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==CRYSTAL STRUCTURE OF LEISHMANIA MAJOR N-MYRISTOYLTRANSFERASE (NMT) WITH BOUND MYRISTOYL-COA AND A PYRAZOLE SULPHONAMIDE LIGAND== | |||
<StructureSection load='4a31' size='340' side='right'caption='[[4a31]], [[Resolution|resolution]] 2.09Å' scene=''> | |||
== Structural highlights == | |||
<table><tr><td colspan='2'>[[4a31]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Leishmania_major Leishmania major]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4A31 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4A31 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]] 2.09Å</td></tr> | |||
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=2CB:6-{[2-(4-METHYLPIPERAZIN-1-YL)ETHYL]AMINO}-N-(1,3,5-TRIMETHYL-1H-PYRAZOL-4-YL)PYRIDINE-3-SULFONAMIDE'>2CB</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</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=4a31 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4a31 OCA], [https://pdbe.org/4a31 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4a31 RCSB], [https://www.ebi.ac.uk/pdbsum/4a31 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4a31 ProSAT]</span></td></tr> | |||
</table> | |||
== 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;"> | |||
== Publication Abstract from PubMed == | |||
N-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<ref>PMID:22148754</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
</div> | |||
<div class="pdbe-citations 4a31" style="background-color:#fffaf0;"></div> | |||
== References == | |||
<references/> | |||
__TOC__ | |||
</StructureSection> | |||
[[Category: Large Structures]] | |||
[[Category: Leishmania major]] | |||
[[Category: Brand S]] | |||
[[Category: Brenk R]] | |||
[[Category: Cleghorn LAT]] | |||
[[Category: Fairlamb AH]] | |||
[[Category: Ferguson MAJ]] | |||
[[Category: Frearson JA]] | |||
[[Category: Gilbert IH]] | |||
[[Category: Hallyburton I]] | |||
[[Category: Harrison JR]] | |||
[[Category: McElroy SP]] | |||
[[Category: Norcross NR]] | |||
[[Category: Norval S]] | |||
[[Category: Read KD]] | |||
[[Category: Robinson DA]] | |||
[[Category: Smith VC]] | |||
[[Category: Spinks D]] | |||
[[Category: Stojanovski L]] | |||
[[Category: Torrie LS]] | |||
[[Category: Wyatt PG]] | |||
Latest revision as of 14:18, 20 December 2023
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
FunctionQ4Q5S8_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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