2wsa: Difference between revisions

← Older edit

Proteopedia Page Contributors and Editors (what is this?)Proteopedia Page Contributors and Editors (what is this?)

OCA

@@ Line 1: / Line 1: @@
-[[Image:2wsa.png|left|200px]]
-<!--
+==Crystal Structure of Leishmania major N-myristoyltransferase (NMT) with bound myristoyl-CoA and a pyrazole sulphonamide ligand (DDD85646)==
-The line below this paragraph, containing "STRUCTURE_2wsa", creates the "Structure Box" on the page.
+<StructureSection load='2wsa' size='340' side='right'caption='[[2wsa]], [[Resolution|resolution]] 1.60&Aring;' scene=''>
-You may change the PDB parameter (which sets the PDB file loaded into the applet)
+== Structural highlights ==
-or the SCENE parameter (which sets the initial scene displayed when the page is loaded),
+<table><tr><td colspan='2'>[[2wsa]] 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=2WSA OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2WSA FirstGlance]. <br>
-or leave the SCENE parameter empty for the default display.
+</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.6&#8491;</td></tr>
--->
+<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=646:2,6-DICHLORO-4-(2-PIPERAZIN-1-YLPYRIDIN-4-YL)-N-(1,3,5-TRIMETHYL-1H-PYRAZOL-4-YL)BENZENESULFONAMIDE'>646</scene>, <scene name='pdbligand=MYA:TETRADECANOYL-COA'>MYA</scene></td></tr>
-{{STRUCTURE_2wsa|  PDB=2wsa  |  SCENE=  }}
+<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=2wsa FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2wsa OCA], [https://pdbe.org/2wsa PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2wsa RCSB], [https://www.ebi.ac.uk/pdbsum/2wsa PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2wsa 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).
+== 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/ws/2wsa_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=2wsa ConSurf].
+<div style="clear:both"></div>
+<div style="background-color:#fffaf0;">
+== Publication Abstract from PubMed ==
+African sleeping sickness or human African trypanosomiasis, caused by Trypanosoma brucei spp., is responsible for approximately 30,000 deaths each year. Available treatments for this disease are poor, with unacceptable efficacy and safety profiles, particularly in the late stage of the disease when the parasite has infected the central nervous system. Here we report the validation of a molecular target and the discovery of associated lead compounds with the potential to address this lack of suitable treatments. Inhibition of this target-T. brucei N-myristoyltransferase-leads to rapid killing of trypanosomes both in vitro and in vivo and cures trypanosomiasis in mice. These high-affinity inhibitors bind into the peptide substrate pocket of the enzyme and inhibit protein N-myristoylation in trypanosomes. The compounds identified have promising pharmaceutical properties and represent an opportunity to develop oral drugs to treat this devastating disease. Our studies validate T. brucei N-myristoyltransferase as a promising therapeutic target for human African trypanosomiasis.
-===CRYSTAL STRUCTURE OF LEISHMANIA MAJOR N-MYRISTOYLTRANSFERASE (NMT) WITH BOUND MYRISTOYL-COA AND A PYRAZOLE SULPHONAMIDE LIGAND (DDD85646)===
+N-myristoyltransferase inhibitors as new leads to treat sleeping sickness.,Frearson JA, Brand S, McElroy SP, Cleghorn LA, Smid O, Stojanovski L, Price HP, Guther ML, Torrie LS, Robinson DA, Hallyburton I, Mpamhanga CP, Brannigan JA, Wilkinson AJ, Hodgkinson M, Hui R, Qiu W, Raimi OG, van Aalten DM, Brenk R, Gilbert IH, Read KD, Fairlamb AH, Ferguson MA, Smith DF, Wyatt PG Nature. 2010 Apr 1;464(7289):728-32. PMID:20360736<ref>PMID:20360736</ref>
+From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
-<!--
+</div>
-The line below this paragraph, {{ABSTRACT_PUBMED_20360736}}, adds the Publication Abstract to the page
+<div class="pdbe-citations 2wsa" style="background-color:#fffaf0;"></div>
-(as it appears on PubMed at http://www.pubmed.gov), where 20360736 is the PubMed ID number.
+== References ==
--->
+<references/>
-{{ABSTRACT_PUBMED_20360736}}
+__TOC__
+</StructureSection>
-==About this Structure==
+[[Category: Large Structures]]
-[[2wsa]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Leishmania_major Leishmania major]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2WSA OCA].
-==Reference==
-<ref group="xtra">PMID:020360736</ref><ref group="xtra">PMID:012488459</ref><references group="xtra"/>
-[[Category: Glycylpeptide N-tetradecanoyltransferase]]
 [[Category: Leishmania major]]
-[[Category: Brand, S.]]
+[[Category: Brand S]]
-[[Category: Fairlamb, A H.]]
+[[Category: Fairlamb AH]]
-[[Category: Ferguson, M A.J.]]
+[[Category: Ferguson MAJ]]
-[[Category: Frearson, J A.]]
+[[Category: Frearson JA]]
-[[Category: Robinson, D A.]]
+[[Category: Robinson DA]]
-[[Category: Sgc, Structural Genomics Consortium.]]
+[[Category: Wyatt PG]]
-[[Category: Wyatt, P G.]]
-[[Category: Acyltransferase]]
-[[Category: Drug discovery]]
-[[Category: Transferase]]