3kr4: Difference between revisions

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-{{Large structure}}
+==Structure of a protease 3==
-{{STRUCTURE_3kr4|  PDB=3kr4  |  SCENE=  }}
+<StructureSection load='3kr4' size='340' side='right' caption='[[3kr4]], [[Resolution|resolution]] 2.00&Aring;' scene=''>
-===Structure of a protease 3===
+== Structural highlights ==
-{{ABSTRACT_PUBMED_20133789}}
+<table><tr><td colspan='2'>[[3kr4]] is a 12 chain structure with sequence from [http://en.wikipedia.org/wiki/Plasmodium_falciparum Plasmodium falciparum]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3KR4 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3KR4 FirstGlance]. <br>
+</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=1PE:PENTAETHYLENE+GLYCOL'>1PE</scene>, <scene name='pdbligand=BES:2-(3-AMINO-2-HYDROXY-4-PHENYL-BUTYRYLAMINO)-4-METHYL-PENTANOIC+ACID'>BES</scene>, <scene name='pdbligand=CO3:CARBONATE+ION'>CO3</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr>
+<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[3kqx|3kqx]], [[3kqz|3kqz]], [[3kr5|3kr5]]</td></tr>
+<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Leucyl_aminopeptidase Leucyl aminopeptidase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.4.11.1 3.4.11.1] </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=3kr4 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3kr4 OCA], [http://www.rcsb.org/pdb/explore.do?structureId=3kr4 RCSB], [http://www.ebi.ac.uk/pdbsum/3kr4 PDBsum]</span></td></tr>
+</table>
+== 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/kr/3kr4_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/chain_selection.php?pdb_ID=2ata ConSurf].
+<div style="clear:both"></div>
+<div style="background-color:#fffaf0;">
+== Publication Abstract from PubMed ==
+Current therapeutics and prophylactics for malaria are under severe challenge as a result of the rapid emergence of drug-resistant parasites. The human malaria parasite Plasmodium falciparum expresses two neutral aminopeptidases, PfA-M1 and PfA-M17, which function in regulating the intracellular pool of amino acids required for growth and development inside the red blood cell. These enzymes are essential for parasite viability and are validated therapeutic targets. We previously reported the x-ray crystal structure of the monomeric PfA-M1 and proposed a mechanism for substrate entry and free amino acid release from the active site. Here, we present the x-ray crystal structure of the hexameric leucine aminopeptidase, PfA-M17, alone and in complex with two inhibitors with antimalarial activity. The six active sites of the PfA-M17 hexamer are arranged in a disc-like fashion so that they are orientated inwards to form a central catalytic cavity; flexible loops that sit at each of the six entrances to the catalytic cavern function to regulate substrate access. In stark contrast to PfA-M1, PfA-M17 has a narrow and hydrophobic primary specificity pocket which accounts for its highly restricted substrate specificity. We also explicate the essential roles for the metal-binding centers in these enzymes (two in PfA-M17 and one in PfA-M1) in both substrate and drug binding. Our detailed understanding of the PfA-M1 and PfA-M17 active sites now permits a rational approach in the development of a unique class of two-target and/or combination antimalarial therapy.
-==About this Structure==
+Structure of the Plasmodium falciparum M17 aminopeptidase and significance for the design of drugs targeting the neutral exopeptidases.,McGowan S, Oellig CA, Birru WA, Caradoc-Davies TT, Stack CM, Lowther J, Skinner-Adams T, Mucha A, Kafarski P, Grembecka J, Trenholme KR, Buckle AM, Gardiner DL, Dalton JP, Whisstock JC Proc Natl Acad Sci U S A. 2010 Feb 9;107(6):2449-54. Epub 2010 Jan 21. PMID:20133789<ref>PMID:20133789</ref>
-[[3kr4]] is a 12 chain structure with sequence from [http://en.wikipedia.org/wiki/Plasmodium_falciparum Plasmodium falciparum]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3KR4 OCA].
+From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
+</div>
 ==See Also==
 *[[Aminopeptidase|Aminopeptidase]]
+== References ==
-==Reference==
+<references/>
-<ref group="xtra">PMID:020133789</ref><references group="xtra"/>
+__TOC__
+</StructureSection>
 [[Category: Leucyl aminopeptidase]]
 [[Category: Plasmodium falciparum]]
-[[Category: McGowan, S.]]
+[[Category: McGowan, S]]
-[[Category: Whisstock, J C.]]
+[[Category: Whisstock, J C]]
 [[Category: Aminopeptidase]]
 [[Category: Hydrolase]]
 [[Category: Protease]]