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5mbx

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Revision as of 07:15, 19 August 2020

Crystal structure of reduced murine N1-acetylpolyamine oxidase in complex with N1-acetylspermine

Structural highlights

5mbx is a 1 chain structure with sequence from Lk3 transgenic mice. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Ligands:	, ,
Gene:	Paox, Pao (LK3 transgenic mice)
Activity:	N(1)-acetylpolyamine oxidase, with EC number 1.5.3.13
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

[PAOX_MOUSE] Flavoenzyme which catalyzes the oxidation of N(1)-acetylspermine to spermidine and is thus involved in the polyamine back-conversion. Can also oxidize N(1)-acetylspermidine to putrescine. Substrate specificity: N(1)-acetylspermine = N(1)-acetylspermidine > N(1),N(12)-diacylspermine >> spermine. Does not oxidize spermidine. Plays an important role in the regulation of polyamine intracellular concentration and has the potential to act as a determinant of cellular sensitivity to the antitumor polyamine analogs.

Publication Abstract from PubMed

N1-Acetylspermine oxidase (APAO) catalyzes the conversion of N1-acetylspermine or N1-acetylspermidine to spermidine or putrescine, respectively, with concomitant formation of N-acetyl-3-aminopropanal and hydrogen peroxide. Here we present the structure of murine APAO in its oxidized holo form and in complex with substrate. The structures provide a basis for understanding molecular details of substrate interaction in vertebrate APAO, highlighting a key role for an asparagine residue in coordinating the N1-acetyl group of the substrate. We applied computational methods to the crystal structures to rationalize previous observations with regard to the substrate charge state. The analysis suggests that APAO features an active site ideally suited for binding of charged polyamines. We also reveal the structure of APAO in complex with the irreversible inhibitor MDL72527. In addition to the covalent adduct, a second MDL72527 molecule is bound in the active site. Binding of MDL72527 is accompanied by altered conformations in the APAO backbone. On the basis of structures of APAO, we discuss the potential for development of specific inhibitors.

The Structure of Murine N1-Acetylspermine Oxidase Reveals Molecular Details of Vertebrate Polyamine Catabolism.,Sjogren T, Wassvik CM, Snijder A, Aagaard A, Kumanomidou T, Barlind L, Kaminski TP, Kashima A, Yokota T, Fjellstrom O Biochemistry. 2017 Jan 12. doi: 10.1021/acs.biochem.6b01140. PMID:28029774^[1]

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

References

↑ Sjogren T, Wassvik CM, Snijder A, Aagaard A, Kumanomidou T, Barlind L, Kaminski TP, Kashima A, Yokota T, Fjellstrom O. The Structure of Murine N1-Acetylspermine Oxidase Reveals Molecular Details of Vertebrate Polyamine Catabolism. Biochemistry. 2017 Jan 12. doi: 10.1021/acs.biochem.6b01140. PMID:28029774 doi:http://dx.doi.org/10.1021/acs.biochem.6b01140

1 Structural highlights
2 Function
3 Publication Abstract from PubMed
4 References

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/5mbx"

@@ Line 1: / Line 1: @@
 ==Crystal structure of reduced murine N1-acetylpolyamine oxidase in complex with N1-acetylspermine==
-<StructureSection load='5mbx' size='340' side='right' caption='[[5mbx]], [[Resolution|resolution]] 1.40&Aring;' scene=''>
+<StructureSection load='5mbx' size='340' side='right'caption='[[5mbx]], [[Resolution|resolution]] 1.40&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[5mbx]] is a 1 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5MBX OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5MBX FirstGlance]. <br>
+<table><tr><td colspan='2'>[[5mbx]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Lk3_transgenic_mice Lk3 transgenic mice]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5MBX OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=5MBX FirstGlance]. <br>
-</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=FAD:FLAVIN-ADENINE+DINUCLEOTIDE'>FAD</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene>, <scene name='pdbligand=SP5:N-[3-({4-[(3-AMINOPROPYL)AMINO]BUTYL}AMINO)PROPYL]ACETAMIDE'>SP5</scene></td></tr>
+</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=FAD:FLAVIN-ADENINE+DINUCLEOTIDE'>FAD</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene>, <scene name='pdbligand=SP5:N-[3-({4-[(3-AMINOPROPYL)AMINO]BUTYL}AMINO)PROPYL]ACETAMIDE'>SP5</scene></td></tr>
+<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">Paox, Pao ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=10090 LK3 transgenic mice])</td></tr>
 <tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/N(1)-acetylpolyamine_oxidase N(1)-acetylpolyamine oxidase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=1.5.3.13 1.5.3.13] </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=5mbx FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5mbx OCA], [http://pdbe.org/5mbx PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5mbx RCSB], [http://www.ebi.ac.uk/pdbsum/5mbx PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5mbx ProSAT]</span></td></tr>
+<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://proteopedia.org/fgij/fg.htm?mol=5mbx FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5mbx OCA], [http://pdbe.org/5mbx PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5mbx RCSB], [http://www.ebi.ac.uk/pdbsum/5mbx PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5mbx ProSAT]</span></td></tr>
 </table>
 == Function ==
@@ Line 23: / Line 24: @@
 __TOC__
 </StructureSection>
+[[Category: Large Structures]]
+[[Category: Lk3 transgenic mice]]
 [[Category: Aagaard, A]]
 [[Category: Barlind, L]]

5mbx

From Proteopedia

Revision as of 07:15, 19 August 2020

Crystal structure of reduced murine N1-acetylpolyamine oxidase in complex with N1-acetylspermine

Structural highlights

Function

Publication Abstract from PubMed

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

Views

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