4cwa | pdb_00004cwa

Structure of Plasmodium Falciparum Spermidine Synthase in Complex with 1H-Benzimidazole-2-pentanamine

spinqualitylabelsall models 4cwa, resolution 2.02Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 4cwa is a 3 chain structure with sequence from Plasmodium falciparum 3D7. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 2.02Å Ligands: 1PG, JA2 Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function Q8II73_PLAF7 Publication Abstract from PubMed The 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 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Spermidine synthase 3D structures

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