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3c6k

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Current revision

Crystal structure of human spermine synthase in complex with spermidine and 5-methylthioadenosine

Structural highlights

3c6k is a 4 chain structure with sequence from Homo sapiens. This structure supersedes the now removed PDB entry 2qfm. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:	X-ray diffraction, Resolution 1.95Å
Ligands:	,
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Disease

SPSY_HUMAN Defects in SMS are the cause of X-linked syndromic mental retardation Snyder-Robinson type (MRXSSR) [MIM:309583. Characterized by moderate intellectual deficit, hypotonia, an unsteady gait, osteoporosis, kyphoscoliosis and facial asymmetry. Transmission is X-linked recessive.^[1]

Function

SPSY_HUMAN Catalyzes the production of spermine from spermidine and decarboxylated S-adenosylmethionine (dcSAM).

Evolutionary Conservation

Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.

Publication Abstract from PubMed

The crystal structures of two ternary complexes of human spermine synthase (EC 2.5.1.22), one with 5'-methylthioadenosine and spermidine and the other with 5'-methylthioadenosine and spermine, have been solved. They show that the enzyme is a dimer of two identical subunits. Each monomer has three domains: a C-terminal domain, which contains the active site and is similar in structure to spermidine synthase; a central domain made up of four beta-strands; and an N-terminal domain with remarkable structural similarity to S-adenosylmethionine decarboxylase, the enzyme that forms the aminopropyl donor substrate. Dimerization occurs mainly through interactions between the N-terminal domains. Deletion of the N-terminal domain led to a complete loss of spermine synthase activity, suggesting that dimerization may be required for activity. The structures provide an outline of the active site and a plausible model for catalysis. The active site is similar to those of spermidine synthases but has a larger substrate-binding pocket able to accommodate longer substrates. Two residues (Asp(201) and Asp(276)) that are conserved in aminopropyltransferases appear to play a key part in the catalytic mechanism, and this role was supported by the results of site-directed mutagenesis. The spermine synthase.5'-methylthioadenosine structure provides a plausible explanation for the potent inhibition of the reaction by this product and the stronger inhibition of spermine synthase compared with spermidine synthase. An analysis to trace possible evolutionary origins of spermine synthase is also described.

Crystal structure of human spermine synthase: implications of substrate binding and catalytic mechanism.,Wu H, Min J, Zeng H, McCloskey DE, Ikeguchi Y, Loppnau P, Michael AJ, Pegg AE, Plotnikov AN J Biol Chem. 2008 Jun 6;283(23):16135-46. Epub 2008 Mar 26. PMID:18367445^[2]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

References

↑ Cason AL, Ikeguchi Y, Skinner C, Wood TC, Holden KR, Lubs HA, Martinez F, Simensen RJ, Stevenson RE, Pegg AE, Schwartz CE. X-linked spermine synthase gene (SMS) defect: the first polyamine deficiency syndrome. Eur J Hum Genet. 2003 Dec;11(12):937-44. PMID:14508504 doi:10.1038/sj.ejhg.5201072
↑ Wu H, Min J, Zeng H, McCloskey DE, Ikeguchi Y, Loppnau P, Michael AJ, Pegg AE, Plotnikov AN. Crystal structure of human spermine synthase: implications of substrate binding and catalytic mechanism. J Biol Chem. 2008 Jun 6;283(23):16135-46. Epub 2008 Mar 26. PMID:18367445 doi:http://dx.doi.org/10.1074/jbc.M710323200

1 Structural highlights
2 Disease
3 Function
4 Evolutionary Conservation
5 Publication Abstract from PubMed
6 See Also
7 References

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/3c6k"

@@ Line 3: / Line 3: @@
 <StructureSection load='3c6k' size='340' side='right'caption='[[3c6k]], [[Resolution|resolution]] 1.95&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[3c6k]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Human Human]. This structure supersedes the now removed PDB entry [http://oca.weizmann.ac.il/oca-bin/send-pdb?obs=1&id=2qfm 2qfm]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3C6K OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3C6K FirstGlance]. <br>
+<table><tr><td colspan='2'>[[3c6k]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. This structure supersedes the now removed PDB entry [http://oca.weizmann.ac.il/oca-bin/send-pdb?obs=1&id=2qfm 2qfm]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3C6K OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3C6K FirstGlance]. <br>
-</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=MTA:5-DEOXY-5-METHYLTHIOADENOSINE'>MTA</scene>, <scene name='pdbligand=SPD:SPERMIDINE'>SPD</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]] 1.95&#8491;</td></tr>
-<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat"><div style='overflow: auto; max-height: 3em;'>[[3c6m|3c6m]]</div></td></tr>
+<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=MTA:5-DEOXY-5-METHYLTHIOADENOSINE'>MTA</scene>, <scene name='pdbligand=SPD:SPERMIDINE'>SPD</scene></td></tr>
-<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">SMS ([https://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr>
-<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[https://en.wikipedia.org/wiki/Spermine_synthase Spermine synthase], with EC number [https://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.5.1.22 2.5.1.22] </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=3c6k FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3c6k OCA], [https://pdbe.org/3c6k PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3c6k RCSB], [https://www.ebi.ac.uk/pdbsum/3c6k PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3c6k ProSAT]</span></td></tr>
 </table>
 == Disease ==
-[[https://www.uniprot.org/uniprot/SPSY_HUMAN SPSY_HUMAN]] Defects in SMS are the cause of X-linked syndromic mental retardation Snyder-Robinson type (MRXSSR) [MIM:[https://omim.org/entry/309583 309583]]. Characterized by moderate intellectual deficit, hypotonia, an unsteady gait, osteoporosis, kyphoscoliosis and facial asymmetry. Transmission is X-linked recessive.<ref>PMID:14508504</ref>
+[https://www.uniprot.org/uniprot/SPSY_HUMAN SPSY_HUMAN] Defects in SMS are the cause of X-linked syndromic mental retardation Snyder-Robinson type (MRXSSR) [MIM:[https://omim.org/entry/309583 309583]. Characterized by moderate intellectual deficit, hypotonia, an unsteady gait, osteoporosis, kyphoscoliosis and facial asymmetry. Transmission is X-linked recessive.<ref>PMID:14508504</ref>
 == Function ==
-[[https://www.uniprot.org/uniprot/SPSY_HUMAN SPSY_HUMAN]] Catalyzes the production of spermine from spermidine and decarboxylated S-adenosylmethionine (dcSAM).
+[https://www.uniprot.org/uniprot/SPSY_HUMAN SPSY_HUMAN] Catalyzes the production of spermine from spermidine and decarboxylated S-adenosylmethionine (dcSAM).
 == Evolutionary Conservation ==
 [[Image:Consurf_key_small.gif|200px|right]]
@@ Line 41: / Line 39: @@
 __TOC__
 </StructureSection>
-[[Category: Human]]
+[[Category: Homo sapiens]]
 [[Category: Large Structures]]
-[[Category: Spermine synthase]]
+[[Category: Arrowsmith CH]]
-[[Category: Arrowsmith, C H]]
+[[Category: Bochkarev A]]
-[[Category: Bochkarev, A]]
+[[Category: Edwards AM]]
-[[Category: Edwards, A M]]
+[[Category: Loppnau P]]
-[[Category: Loppnau, P]]
+[[Category: Min J]]
-[[Category: Min, J]]
+[[Category: Pegg AE]]
-[[Category: Pegg, A E]]
+[[Category: Plotnikov AN]]
-[[Category: Plotnikov, A N]]
+[[Category: Sundstrom M]]
-[[Category: Structural genomic]]
+[[Category: Weigelt J]]
-[[Category: Sundstrom, M]]
+[[Category: Wu H]]
-[[Category: Weigelt, J]]
+[[Category: Zeng H]]
-[[Category: Wu, H]]
-[[Category: Zeng, H]]
-[[Category: Phosphoprotein]]
-[[Category: Sgc]]
-[[Category: Spermidine aminopropyltransferase]]
-[[Category: Spmsy]]
-[[Category: Transferase]]

3c6k

From Proteopedia

Current revision

Crystal structure of human spermine synthase in complex with spermidine and 5-methylthioadenosine

Structural highlights

Disease

Function

Evolutionary Conservation

Publication Abstract from PubMed

See Also

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

Views

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