2jev

From Proteopedia

(Difference between revisions)

Current revision

Crystal structure of human spermine,spermidine acetyltransferase in complex with a bisubstrate analog (N1-acetylspermine-S-CoA).

Structural highlights

2jev 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 2.3Å
Ligands:
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Disease

SAT1_HUMAN Defects in SAT1 may be a cause of keratosis follicularis spinulosa decalvans X-linked (KFSDX) [MIM:308800. A rare disorder affecting the skin and the eye. Affected men show thickening of the skin of the neck, ears, and extremities, especially the palms and soles, loss of eyebrows, eyelashes and beard, thickening of the eyelids with blepharitis and ectropion, and corneal degeneration.^[1] ^[2]

Function

SAT1_HUMAN Enzyme which catalyzes the acetylation of polyamines. Substrate specificity: norspermidine = spermidine >> spermine > N(1)-acetylspermine > putrescine. This highly regulated enzyme allows a fine attenuation of the intracellular concentration of polyamines. Also involved in the regulation of polyamine transport out of cells. Acts on 1,3-diaminopropane, 1,5-diaminopentane, putrescine, spermidine (forming N(1)- and N(8)-acetylspermidine), spermine, N(1)-acetylspermidine and N(8)-acetylspermidine.

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 N1-acetylation of spermidine and spermine by spermidine/spermine acetyltransferase (SSAT) is a crucial step in the regulation of the cellular polyamine levels in eukaryotic cells. Altered polyamine levels are associated with a variety of cancers as well as other diseases, and key enzymes in the polyamine pathway, including SSAT, are being explored as potential therapeutic drug targets. We have expressed and purified human SSAT in Escherichia coli and characterized its kinetic and chemical mechanism. Initial velocity and inhibition studies support a random sequential mechanism for the enzyme. The bisubstrate analogue, N1-spermine-acetyl-coenzyme A, exhibited linear, competitive inhibition against both substrates with a true Ki of 6 nM. The pH-activity profile was bell-shaped, depending on the ionization state of two groups exhibiting apparent pKa values of 7.27 and 8.87. The three-dimensional crystal structure of SSAT with bound bisubstrate inhibitor was determined at 2.3 A resolution. The structure of the SSAT-spermine-acetyl-coenzyme A complex suggested that Tyr140 acts as general acid and Glu92, through one or more water molecules, acts as the general base during catalysis. On the basis of kinetic properties, pH dependence, and structural information, we propose an acid/base-assisted reaction catalyzed by SSAT, involving a ternary complex.

Mechanistic and structural analysis of human spermidine/spermine N1-acetyltransferase.,Hegde SS, Chandler J, Vetting MW, Yu M, Blanchard JS Biochemistry. 2007 Jun 19;46(24):7187-95. Epub 2007 May 22. PMID:17516632^[3]

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

References

↑ Oosterwijk JC, Richard G, van der Wielen MJ, van de Vosse E, Harth W, Sandkuijl LA, Bakker E, van Ommen GJ. Molecular genetic analysis of two families with keratosis follicularis spinulosa decalvans: refinement of gene localization and evidence for genetic heterogeneity. Hum Genet. 1997 Oct;100(5-6):520-4. PMID:9341865
↑ Gimelli G, Giglio S, Zuffardi O, Alhonen L, Suppola S, Cusano R, Lo Nigro C, Gatti R, Ravazzolo R, Seri M. Gene dosage of the spermidine/spermine N(1)-acetyltransferase ( SSAT) gene with putrescine accumulation in a patient with a Xp21.1p22.12 duplication and keratosis follicularis spinulosa decalvans (KFSD). Hum Genet. 2002 Sep;111(3):235-41. Epub 2002 Aug 1. PMID:12215835 doi:10.1007/s00439-002-0791-6
↑ Hegde SS, Chandler J, Vetting MW, Yu M, Blanchard JS. Mechanistic and structural analysis of human spermidine/spermine N1-acetyltransferase. Biochemistry. 2007 Jun 19;46(24):7187-95. Epub 2007 May 22. PMID:17516632 doi:10.1021/bi700256z

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/2jev"

@@ Line 1: / Line 1: @@
-==CRYSTAL STRUCTURE OF HUMAN SPERMINE,SPERMIDINE ACETYLTRANSFERASE IN COMPLEX WITH A BISUBSTRATE ANALOG (N1-ACETYLSPERMINE-S-COA).==
-<StructureSection load='2jev' size='340' side='right' caption='[[2jev]], [[Resolution|resolution]] 2.30&Aring;' scene=''>
+==Crystal structure of human spermine,spermidine acetyltransferase in complex with a bisubstrate analog (N1-acetylspermine-S-CoA).==
+<StructureSection load='2jev' size='340' side='right'caption='[[2jev]], [[Resolution|resolution]] 2.30&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[2jev]] 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=2JEV OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2JEV FirstGlance]. <br>
+<table><tr><td colspan='2'>[[2jev]] 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=2JEV OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2JEV FirstGlance]. <br>
-</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=NHQ:(3R)-27-AMINO-3-HYDROXY-2,2-DIMETHYL-4,8,14-TRIOXO-12-THIA-5,9,15,19,24-PENTAAZAHEPTACOS-1-YL+[(2S,3R,4S,5S)-5-(6-AMINO-9H-PURIN-9-YL)-4-HYDROXY-3-(PHOSPHONOOXY)TETRAHYDROFURAN-2-YL]METHYL+DIHYDROGEN+DIPHOSPHATE'>NHQ</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]] 2.3&#8491;</td></tr>
-<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[2b3u|2b3u]], [[2b3v|2b3v]], [[2b4b|2b4b]], [[2b4d|2b4d]], [[2b58|2b58]], [[2b5g|2b5g]], [[2f5i|2f5i]], [[2fxf|2fxf]], [[2g3t|2g3t]]</td></tr>
+<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=NHQ:(3R)-27-AMINO-3-HYDROXY-2,2-DIMETHYL-4,8,14-TRIOXO-12-THIA-5,9,15,19,24-PENTAAZAHEPTACOS-1-YL+[(2S,3R,4S,5S)-5-(6-AMINO-9H-PURIN-9-YL)-4-HYDROXY-3-(PHOSPHONOOXY)TETRAHYDROFURAN-2-YL]METHYL+DIHYDROGEN+DIPHOSPHATE'>NHQ</scene></td></tr>
-<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Diamine_N-acetyltransferase Diamine N-acetyltransferase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.3.1.57 2.3.1.57] </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=2jev FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2jev OCA], [https://pdbe.org/2jev PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2jev RCSB], [https://www.ebi.ac.uk/pdbsum/2jev PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2jev 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=2jev FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2jev OCA], [http://www.rcsb.org/pdb/explore.do?structureId=2jev RCSB], [http://www.ebi.ac.uk/pdbsum/2jev PDBsum]</span></td></tr>
 </table>
+== Disease ==
+[https://www.uniprot.org/uniprot/SAT1_HUMAN SAT1_HUMAN] Defects in SAT1 may be a cause of keratosis follicularis spinulosa decalvans X-linked (KFSDX) [MIM:[https://omim.org/entry/308800 308800]. A rare disorder affecting the skin and the eye. Affected men show thickening of the skin of the neck, ears, and extremities, especially the palms and soles, loss of eyebrows, eyelashes and beard, thickening of the eyelids with blepharitis and ectropion, and corneal degeneration.<ref>PMID:9341865</ref> <ref>PMID:12215835</ref>
+== Function ==
+[https://www.uniprot.org/uniprot/SAT1_HUMAN SAT1_HUMAN] Enzyme which catalyzes the acetylation of polyamines. Substrate specificity: norspermidine = spermidine >> spermine > N(1)-acetylspermine > putrescine. This highly regulated enzyme allows a fine attenuation of the intracellular concentration of polyamines. Also involved in the regulation of polyamine transport out of cells. Acts on 1,3-diaminopropane, 1,5-diaminopentane, putrescine, spermidine (forming N(1)- and N(8)-acetylspermidine), spermine, N(1)-acetylspermidine and N(8)-acetylspermidine.
 == Evolutionary Conservation ==
 [[Image:Consurf_key_small.gif|200px|right]]
 Check<jmol>
   <jmolCheckbox>
-    <scriptWhenChecked>select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/je/2jev_consurf.spt"</scriptWhenChecked>
+    <scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/je/2jev_consurf.spt"</scriptWhenChecked>
     <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked>
     <text>to colour the structure by Evolutionary Conservation</text>
   </jmolCheckbox>
-</jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/chain_selection.php?pdb_ID=2ata ConSurf].
+</jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/main_output.php?pdb_ID=2jev ConSurf].
 <div style="clear:both"></div>
 <div style="background-color:#fffaf0;">
@@ Line 26: / Line 30: @@
 From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
 </div>
+<div class="pdbe-citations 2jev" style="background-color:#fffaf0;"></div>
 ==See Also==
@@ Line 33: / Line 38: @@
 __TOC__
 </StructureSection>
-[[Category: Diamine N-acetyltransferase]]
 [[Category: Homo sapiens]]
-[[Category: Blanchard, J S]]
+[[Category: Large Structures]]
-[[Category: Chandler, J]]
+[[Category: Blanchard JS]]
-[[Category: Hegde, S S]]
+[[Category: Chandler J]]
-[[Category: Vetting, M W]]
+[[Category: Hegde SS]]
-[[Category: Yu, M]]
+[[Category: Vetting MW]]
-[[Category: Acetyltransferase]]
+[[Category: Yu M]]
-[[Category: Acyltransferase]]
-[[Category: Bisubstrate]]
-[[Category: Gcn5 related n-acetyltransferase]]
-[[Category: Gnat]]
-[[Category: Polyamine biosynthesis]]
-[[Category: Spermidine]]
-[[Category: Spermine]]
-[[Category: Transferase]]

2jev

From Proteopedia

Current revision

Crystal structure of human spermine,spermidine acetyltransferase in complex with a bisubstrate analog (N1-acetylspermine-S-CoA).

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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