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| | ==Dodecameric structure of spermidine N-acetyltransferase SpeG from Vibrio cholerae O1 biovar eltor== | | ==Dodecameric structure of spermidine N-acetyltransferase SpeG from Vibrio cholerae O1 biovar eltor== |
| - | <StructureSection load='4jjx' size='340' side='right' caption='[[4jjx]], [[Resolution|resolution]] 2.83Å' scene=''> | + | <StructureSection load='4jjx' size='340' side='right'caption='[[4jjx]], [[Resolution|resolution]] 2.83Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[4jjx]] is a 3 chain structure with sequence from [http://en.wikipedia.org/wiki/Vibch Vibch]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4JJX OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4JJX FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[4jjx]] is a 3 chain structure with sequence from [https://en.wikipedia.org/wiki/Vibrio_cholerae_O1_biovar_El_Tor_str._N16961 Vibrio cholerae O1 biovar El Tor str. N16961]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4JJX OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4JJX FirstGlance]. <br> |
| - | </td></tr><tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[3eg7|3eg7]]</td></tr> | + | </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=4jjx FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4jjx OCA], [https://pdbe.org/4jjx PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4jjx RCSB], [https://www.ebi.ac.uk/pdbsum/4jjx PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4jjx ProSAT]</span></td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">VC_A0947 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=243277 VIBCH])</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=4jjx FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4jjx OCA], [http://pdbe.org/4jjx PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4jjx RCSB], [http://www.ebi.ac.uk/pdbsum/4jjx PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4jjx ProSAT]</span></td></tr> | + | |
| | </table> | | </table> |
| | + | == Function == |
| | + | [https://www.uniprot.org/uniprot/ATDA_VIBCH ATDA_VIBCH] Involved in the protection against polyamine toxicity by regulating their concentration. Catalyzes the transfer of an acetyl group from acetyl coenzyme A (AcCoA) to the primary amino groups of spermidine to yield N(1)- and N(8)-acetylspermidine. It can use polyamines such as spermine and N(1)-acetylspermine, but not putrescine or cadaverine.<ref>PMID:23184347</ref> <ref>PMID:25623305</ref> |
| | <div style="background-color:#fffaf0;"> | | <div style="background-color:#fffaf0;"> |
| | == Publication Abstract from PubMed == | | == Publication Abstract from PubMed == |
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| | </div> | | </div> |
| | <div class="pdbe-citations 4jjx" style="background-color:#fffaf0;"></div> | | <div class="pdbe-citations 4jjx" style="background-color:#fffaf0;"></div> |
| | + | |
| | + | ==See Also== |
| | + | *[[Spermidine/spermine N-acetyltransferase|Spermidine/spermine N-acetyltransferase]] |
| | == References == | | == References == |
| | <references/> | | <references/> |
| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Vibch]] | + | [[Category: Large Structures]] |
| - | [[Category: Anderson, W F]] | + | [[Category: Vibrio cholerae O1 biovar El Tor str. N16961]] |
| - | [[Category: Structural genomic]] | + | [[Category: Anderson WF]] |
| - | [[Category: Filippova, E V]] | + | [[Category: Filippova EV]] |
| - | [[Category: Kiryukhina, O]] | + | [[Category: Kiryukhina O]] |
| - | [[Category: Kuhn, M L]] | + | [[Category: Kuhn ML]] |
| - | [[Category: Minasov, G]] | + | [[Category: Minasov G]] |
| - | [[Category: Shuvalova, L]] | + | [[Category: Shuvalova L]] |
| - | [[Category: Csgid]]
| + | |
| - | [[Category: National institute of allergy and infectious disease]]
| + | |
| - | [[Category: Niaid]]
| + | |
| - | [[Category: Transferase]]
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| Structural highlights
Function
ATDA_VIBCH Involved in the protection against polyamine toxicity by regulating their concentration. Catalyzes the transfer of an acetyl group from acetyl coenzyme A (AcCoA) to the primary amino groups of spermidine to yield N(1)- and N(8)-acetylspermidine. It can use polyamines such as spermine and N(1)-acetylspermine, but not putrescine or cadaverine.[1] [2]
Publication Abstract from PubMed
Spermidine N-acetyltransferase, encoded by the gene speG, catalyzes the initial step in the degradation of polyamines and is a critical enzyme for determining the polyamine concentrations in bacteria. In Escherichia coli, studies have shown that SpeG is the enzyme responsible for acetylating spermidine under stress conditions and for preventing spermidine toxicity. Not all bacteria contain speG, and many bacterial pathogens have developed strategies to either acquire or silence it for pathogenesis. Here, we present thorough kinetic analyses combined with structural characterization of the VCA0947 SpeG enzyme from the important human pathogen Vibrio cholerae. Our studies revealed the unexpected presence of a previously unknown allosteric site and an unusual dodecameric structure for a member of the Gcn5-related N-acetyltransferase superfamily. We show that SpeG forms dodecamers in solution and in crystals and describe its three-dimensional structure in several ligand-free and liganded structures. Importantly, these structural data define the first view of a polyamine bound in an allosteric site of an N-acetyltransferase. Kinetic characterization of SpeG from V. cholerae showed that it acetylates spermidine and spermine. The behavior of this enzyme is complex and exhibits sigmoidal curves and substrate inhibition. We performed a detailed non-linear regression kinetic analysis to simultaneously fit families of substrate saturation curves to uncover a simple kinetic mechanism that explains the apparent complexity of this enzyme. Our results provide a fundamental understanding of the bacterial SpeG enzyme, which will be key toward understanding the regulation of polyamine levels in bacteria during pathogenesis.
A Novel Polyamine Allosteric Site of SpeG from Vibrio cholerae Is Revealed by Its Dodecameric Structure.,Filippova EV, Kuhn ML, Osipiuk J, Kiryukhina O, Joachimiak A, Ballicora MA, Anderson WF J Mol Biol. 2015 Mar 27;427(6 Pt B):1316-34. doi: 10.1016/j.jmb.2015.01.009. Epub, 2015 Jan 23. PMID:25623305[3]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Kuhn ML, Majorek KA, Minor W, Anderson WF. Broad-substrate screen as a tool to identify substrates for bacterial Gcn5-related N-acetyltransferases with unknown substrate specificity. Protein Sci. 2013 Feb;22(2):222-30. doi: 10.1002/pro.2199. Epub 2012 Dec 17. PMID:23184347 doi:http://dx.doi.org/10.1002/pro.2199
- ↑ Filippova EV, Kuhn ML, Osipiuk J, Kiryukhina O, Joachimiak A, Ballicora MA, Anderson WF. A Novel Polyamine Allosteric Site of SpeG from Vibrio cholerae Is Revealed by Its Dodecameric Structure. J Mol Biol. 2015 Mar 27;427(6 Pt B):1316-34. doi: 10.1016/j.jmb.2015.01.009. Epub, 2015 Jan 23. PMID:25623305 doi:http://dx.doi.org/10.1016/j.jmb.2015.01.009
- ↑ Filippova EV, Kuhn ML, Osipiuk J, Kiryukhina O, Joachimiak A, Ballicora MA, Anderson WF. A Novel Polyamine Allosteric Site of SpeG from Vibrio cholerae Is Revealed by Its Dodecameric Structure. J Mol Biol. 2015 Mar 27;427(6 Pt B):1316-34. doi: 10.1016/j.jmb.2015.01.009. Epub, 2015 Jan 23. PMID:25623305 doi:http://dx.doi.org/10.1016/j.jmb.2015.01.009
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