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==Structure of Plasmodium Falciparum Spermidine Synthase in Complex with 1H-Benzimidazole-2-pentanamine== | ==Structure of Plasmodium Falciparum Spermidine Synthase in Complex with 1H-Benzimidazole-2-pentanamine== | ||
<StructureSection load='4cwa' size='340' side='right' caption='[[4cwa]], [[Resolution|resolution]] 2.02Å' scene=''> | <StructureSection load='4cwa' size='340' side='right' caption='[[4cwa]], [[Resolution|resolution]] 2.02Å' scene=''> | ||
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</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=1PG:2-(2-{2-[2-(2-METHOXY-ETHOXY)-ETHOXY]-ETHOXY}-ETHOXY)-ETHANOL'>1PG</scene>, <scene name='pdbligand=JA2:5-(1H-BENZIMIDAZOL-2-YL)PENTAN-1-AMINE'>JA2</scene></td></tr> | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=1PG:2-(2-{2-[2-(2-METHOXY-ETHOXY)-ETHOXY]-ETHOXY}-ETHOXY)-ETHANOL'>1PG</scene>, <scene name='pdbligand=JA2:5-(1H-BENZIMIDAZOL-2-YL)PENTAN-1-AMINE'>JA2</scene></td></tr> | ||
<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Spermidine_synthase Spermidine synthase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.5.1.16 2.5.1.16] </span></td></tr> | <tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Spermidine_synthase Spermidine synthase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.5.1.16 2.5.1.16] </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=4cwa FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4cwa OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4cwa RCSB], [http://www.ebi.ac.uk/pdbsum/4cwa 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=4cwa FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4cwa OCA], [http://pdbe.org/4cwa PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4cwa RCSB], [http://www.ebi.ac.uk/pdbsum/4cwa PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4cwa ProSAT]</span></td></tr> | ||
</table> | </table> | ||
<div style="background-color:#fffaf0;"> | <div style="background-color:#fffaf0;"> | ||
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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 4cwa" style="background-color:#fffaf0;"></div> | |||
==See Also== | |||
*[[Spermidine Synthase|Spermidine Synthase]] | |||
== References == | == References == | ||
<references/> | <references/> | ||
Revision as of 20:02, 2 January 2017
Structure of Plasmodium Falciparum Spermidine Synthase in Complex with 1H-Benzimidazole-2-pentanamineStructure of Plasmodium Falciparum Spermidine Synthase in Complex with 1H-Benzimidazole-2-pentanamine
Structural highlights
Publication Abstract from PubMedThe enzymes of the polyamine-biosynthesis pathway have been proposed to be promising drug targets in the treatment of malaria. Spermidine synthase (SpdS; putrescine aminopropyltransferase) catalyzes the transfer of the aminopropyl moiety from decarboxylated S-adenosylmethionine to putrescine, leading to the formation of spermidine and 5'-methylthioadenosine (MTA). In this work, X-ray crystallography was used to examine ligand complexes of SpdS from the malaria parasite Plasmodium falciparum (PfSpdS). Five crystal structures were determined of PfSpdS in complex with MTA and the substrate putrescine, with MTA and spermidine, which was obtained as a result of the enzymatic reaction taking place within the crystals, with dcAdoMet and the inhibitor 4-methylaniline, with MTA and 4-aminomethylaniline, and with a compound predicted in earlier in silico screening to bind to the active site of the enzyme, benzimidazol-(2-yl)pentan-1-amine (BIPA). In contrast to the other inhibitors tested, the complex with BIPA was obtained without any ligand bound to the dcAdoMet-binding site of the enzyme. The complexes with the aniline compounds and BIPA revealed a new mode of ligand binding to PfSpdS. The observed binding mode of the ligands, and the interplay between the two substrate-binding sites and the flexible gatekeeper loop, can be used in the design of new approaches in the search for new inhibitors of SpdS. Three-dimensional structures of Plasmodium falciparum spermidine synthase with bound inhibitors suggest new strategies for drug design.,Sprenger J, Svensson B, Halander J, Carey J, Persson L, Al-Karadaghi S Acta Crystallogr D Biol Crystallogr. 2015 Mar 1;71(Pt 3):484-93. doi:, 10.1107/S1399004714027011. Epub 2015 Feb 26. PMID:25760598[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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