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| | ==Crystal Structure of human Spermidine Synthase in Complex with decarboxylated S-adenosylhomocysteine== | | ==Crystal Structure of human Spermidine Synthase in Complex with decarboxylated S-adenosylhomocysteine== |
| - | <StructureSection load='3rw9' size='340' side='right' caption='[[3rw9]], [[Resolution|resolution]] 2.00Å' scene=''> | + | <StructureSection load='3rw9' size='340' side='right'caption='[[3rw9]], [[Resolution|resolution]] 2.00Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[3rw9]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3RW9 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3RW9 FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[3rw9]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3RW9 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3RW9 FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=DSH:5-S-(3-AMINOPROPYL)-5-THIOADENOSINE'>DSH</scene></td></tr> | + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2Å</td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">SRM, SPS1, SRML1 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr> | + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=DSH:5-S-(3-AMINOPROPYL)-5-THIOADENOSINE'>DSH</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='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=3rw9 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3rw9 OCA], [https://pdbe.org/3rw9 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3rw9 RCSB], [https://www.ebi.ac.uk/pdbsum/3rw9 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3rw9 ProSAT]</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=3rw9 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3rw9 OCA], [http://pdbe.org/3rw9 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=3rw9 RCSB], [http://www.ebi.ac.uk/pdbsum/3rw9 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=3rw9 ProSAT]</span></td></tr> | + | |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/SPEE_HUMAN 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. | + | [https://www.uniprot.org/uniprot/SPEE_HUMAN 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. |
| - | <div style="background-color:#fffaf0;">
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| - | == Publication Abstract from PubMed ==
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| - | 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.
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| - | 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<ref>PMID:21898642</ref>
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| - | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
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| - | </div>
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| - | <div class="pdbe-citations 3rw9" style="background-color:#fffaf0;"></div>
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| | | | |
| | ==See Also== | | ==See Also== |
| - | *[[Spermidine Synthase|Spermidine Synthase]] | + | *[[Spermidine synthase 3D structures|Spermidine synthase 3D structures]] |
| - | == References ==
| + | |
| - | <references/>
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| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Human]] | + | [[Category: Homo sapiens]] |
| - | [[Category: Spermidine synthase]] | + | [[Category: Large Structures]] |
| - | [[Category: Ealick, S E]] | + | [[Category: Ealick SE]] |
| - | [[Category: III, J A.Secrist]]
| + | [[Category: McCloskey DE]] |
| - | [[Category: McCloskey, D E]] | + | [[Category: Pegg AE]] |
| - | [[Category: Pegg, A E]] | + | [[Category: Seckute J]] |
| - | [[Category: Seckute, J]] | + | [[Category: Secrist III JA]] |
| - | [[Category: Thomas, H J]] | + | [[Category: Thomas HJ]] |
| - | [[Category: Aminopropyltransferase]] | + | |
| - | [[Category: Transferase]]
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