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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]] 2.00&Aring;' scene=''>
<StructureSection load='3rw9' size='340' side='right'caption='[[3rw9]], [[Resolution|resolution]] 2.00&Aring;' scene=''>
== Structural highlights ==
== Structural highlights ==
<table><tr><td colspan='2'>[[3rw9]] is a 2 chain structure with sequence from [http://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 [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]] 2&#8491;</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 Homo sapiens])</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://www.rcsb.org/pdb/explore.do?structureId=3rw9 RCSB], [http://www.ebi.ac.uk/pdbsum/3rw9 PDBsum]</span></td></tr>
</table>
</table>
<div style="background-color:#fffaf0;">
== Function ==
== Publication Abstract from PubMed ==
[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.
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<ref>PMID:21898642</ref>
 
From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>


==See Also==
==See Also==
*[[Spermidine Synthase|Spermidine Synthase]]
*[[Spermidine synthase 3D structures|Spermidine synthase 3D structures]]
== References ==
<references/>
__TOC__
__TOC__
</StructureSection>
</StructureSection>
[[Category: Homo sapiens]]
[[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]]

Latest revision as of 12:45, 1 March 2024

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.
Method:X-ray diffraction, Resolution 2Å
Ligands:
Resources:FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

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.

See Also

3rw9, resolution 2.00Å

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