View source for 2wuu


==Structure of N-myristoyltransferase from L. donovani==
<StructureSection load='2wuu' size='340' side='right'caption='[[2wuu]], [[Resolution|resolution]] 1.42&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[2wuu]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Leishmania_donovani Leishmania donovani]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2WUU OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2WUU 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]] 1.42&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=NHW:2-OXOPENTADECYL-COA'>NHW</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=2wuu FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2wuu OCA], [https://pdbe.org/2wuu PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2wuu RCSB], [https://www.ebi.ac.uk/pdbsum/2wuu PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2wuu ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/D0AB09_LEIDO D0AB09_LEIDO] Adds a myristoyl group to the N-terminal glycine residue of certain cellular proteins.[RuleBase:RU000586]
== Evolutionary Conservation ==
[[Image:Consurf_key_small.gif|200px|right]]
Check<jmol>
  <jmolCheckbox>
    <scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/wu/2wuu_consurf.spt"</scriptWhenChecked>
    <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked>
    <text>to colour the structure by Evolutionary Conservation</text>
  </jmolCheckbox>
</jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/main_output.php?pdb_ID=2wuu ConSurf].
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== Publication Abstract from PubMed ==
N-Myristoyltransferase (NMT) catalyses the attachment of the 14-carbon saturated fatty acid, myristate, to the amino-terminal glycine residue of a subset of eukaryotic proteins that function in multiple cellular processes, including vesicular protein trafficking and signal transduction. In these pathways, N-myristoylation facilitates association of substrate proteins with membranes or the hydrophobic domains of other partner peptides. NMT function is essential for viability in all cell types tested to date, demonstrating that this enzyme has potential as a target for drug development. Here, we provide genetic evidence that NMT is likely to be essential for viability in insect stages of the pathogenic protozoan parasite, Leishmania donovani, causative agent of the tropical infectious disease, visceral leishmaniasis. The open reading frame of L. donovani NMT has been amplified and used to overproduce active recombinant enzyme in Escherichia coli, as demonstrated by gel mobility shift assays of ligand binding and peptide-myristoylation activity in scintillation proximity assays. The purified protein has been crystallized in complex with the non-hydrolysable substrate analogue S-(2-oxo)pentadecyl-CoA, and its structure was solved by molecular replacement at 1.4 A resolution. The structure has as its defining feature a 14-stranded twisted beta-sheet on which helices are packed so as to form an extended and curved substrate-binding groove running across two protein lobes. The fatty acyl-CoA is largely buried in the N-terminal lobe, its binding leading to the loosening of a flap, which in unliganded NMT structures, occludes the protein substrate binding site in the carboxy-terminal lobe. These studies validate L. donovani NMT as a potential target for development of new therapeutic agents against visceral leishmaniasis.

N-myristoyltransferase from Leishmania donovani: structural and functional characterisation of a potential drug target for visceral leishmaniasis.,Brannigan JA, Smith BA, Yu Z, Brzozowski AM, Hodgkinson MR, Maroof A, Price HP, Meier F, Leatherbarrow RJ, Tate EW, Smith DF, Wilkinson AJ J Mol Biol. 2010 Mar 5;396(4):985-99. Epub 2009 Dec 28. PMID:20036251<ref>PMID:20036251</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Large Structures]]
[[Category: Leishmania donovani]]
[[Category: Brannigan JA]]
[[Category: Brzozowski AM]]
[[Category: Hodgkinson MR]]
[[Category: Leatherbarrow RJ]]
[[Category: Smith BA]]
[[Category: Smith DF]]
[[Category: Tate EW]]
[[Category: Wilkinson AJ]]
[[Category: Yu Z]]