3rw9

Crystal Structure of human Spermidine Synthase in Complex with decarboxylated S-adenosylhomocysteineCrystal Structure of human Spermidine Synthase in Complex with decarboxylated S-adenosylhomocysteine

Structural highlights 3rw9 is a 2 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Ligands: Gene: SRM, SPS1, SRML1 (Homo sapiens) Activity: Spermidine synthase, with EC number 2.5.1.16 Resources: FirstGlance, OCA, RCSB, PDBsum Function [SPEE_HUMAN] Catalyzes the production of spermidine from putrescine and decarboxylated S-adenosylmethionine (dcSAM). Has a strong preference for putrescine as substrate, and has very low activity towards 1,3-diaminopropane. Has extremely low activity towards spermidine. Publication Abstract from PubMed Aminopropyltransferases are essential enzymes that form polyamines in eukaryotic and most prokaryotic cells. Spermidine synthase (SpdS) is one of the most well-studied enzymes in this biosynthetic pathway. The enzyme uses decarboxylated S-adenosylmethionine and a short-chain polyamine (putrescine) to make a medium-chain polyamine (spermidine) and 5'-deoxy-5'-methylthioadenosine as a byproduct. Here, we report a new spermidine synthase inhibitor, decarboxylated S-adenosylhomocysteine (dcSAH). The inhibitor was synthesized, and dose-dependent inhibition of human, Thermatoga maritima, and Plasmodium falciparum spermidine synthases, as well as functionally homologous human spermine synthase, was determined. The human SpdS/dcSAH complex structure was determined by X-ray crystallography at 2.0 A resolution and showed consistent active site positioning and coordination with previously known structures. Isothermal calorimetry binding assays confirmed inhibitor binding to human SpdS with K(d) of 1.1 +/- 0.3 muM in the absence of putrescine and 3.2 +/- 0.1 muM in the presence of putrescine. These results indicate a potential for further inhibitor development based on the dcSAH scaffold. Binding and inhibition of human spermidine synthase by decarboxylated S-adenosylhomocysteine.,Seckute J, McCloskey DE, Thomas HJ, Secrist JA 3rd, Pegg AE, Ealick SE Protein Sci. 2011 Aug 24. doi: 10.1002/pro.717. PMID:21898642 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Spermidine Synthase

spinqualitylabelsall models 3rw9, resolution 2.00Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image