1h86
From Proteopedia
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| - | [[Image:1h86.gif|left|200px]]<br /><applet load="1h86" size=" | + | [[Image:1h86.gif|left|200px]]<br /><applet load="1h86" size="350" color="white" frame="true" align="right" spinBox="true" |
caption="1h86, resolution 2.0Å" /> | caption="1h86, resolution 2.0Å" /> | ||
'''COVALENT ADDUCT BETWEEN POLYAMINE OXIDASE AND N1ETHYLN11 ((CYCLOHEPTYL)METHYL)4,8DIAZAUNDECANE AT PH 7.0'''<br /> | '''COVALENT ADDUCT BETWEEN POLYAMINE OXIDASE AND N1ETHYLN11 ((CYCLOHEPTYL)METHYL)4,8DIAZAUNDECANE AT PH 7.0'''<br /> | ||
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==About this Structure== | ==About this Structure== | ||
| - | 1H86 is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Zea_mays Zea mays] with NAG and FAD as [http://en.wikipedia.org/wiki/ligands ligands]. Active as [http://en.wikipedia.org/wiki/Polyamine_oxidase Polyamine oxidase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=1.5.3.11 1.5.3.11] Known structural/functional Sites: <scene name='pdbsite=FAA:Fad Binding Site For Chain A'>FAA</scene>, <scene name='pdbsite=FAB:Fad Binding Site For Chain B'>FAB</scene>, <scene name='pdbsite=FAC:Fad Binding Site For Chain C'>FAC</scene>, <scene name='pdbsite=NBA:Nba Binding Site For Chain A'>NBA</scene>, <scene name='pdbsite=NBB:Nba Binding Site For Chain B'>NBB</scene> and <scene name='pdbsite=NBC:Nba Binding Site For Chain C'>NBC</scene>. Full crystallographic information is available from [http:// | + | 1H86 is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Zea_mays Zea mays] with <scene name='pdbligand=NAG:'>NAG</scene> and <scene name='pdbligand=FAD:'>FAD</scene> as [http://en.wikipedia.org/wiki/ligands ligands]. Active as [http://en.wikipedia.org/wiki/Polyamine_oxidase Polyamine oxidase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=1.5.3.11 1.5.3.11] Known structural/functional Sites: <scene name='pdbsite=FAA:Fad+Binding+Site+For+Chain+A'>FAA</scene>, <scene name='pdbsite=FAB:Fad+Binding+Site+For+Chain+B'>FAB</scene>, <scene name='pdbsite=FAC:Fad+Binding+Site+For+Chain+C'>FAC</scene>, <scene name='pdbsite=NBA:Nba+Binding+Site+For+Chain+A'>NBA</scene>, <scene name='pdbsite=NBB:Nba+Binding+Site+For+Chain+B'>NBB</scene> and <scene name='pdbsite=NBC:Nba+Binding+Site+For+Chain+C'>NBC</scene>. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1H86 OCA]. |
==Reference== | ==Reference== | ||
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[[Category: oxidoreductase]] | [[Category: oxidoreductase]] | ||
| - | ''Page seeded by [http:// | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sun Feb 3 09:47:37 2008'' |
Revision as of 07:47, 3 February 2008
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COVALENT ADDUCT BETWEEN POLYAMINE OXIDASE AND N1ETHYLN11 ((CYCLOHEPTYL)METHYL)4,8DIAZAUNDECANE AT PH 7.0
Overview
Polyamine oxidase (PAO) carries out the FAD-dependent oxidation of the, secondary amino groups of spermidine and spermine, a key reaction in the, polyamine catabolism. The active site of PAO consists of a 30 A long, U-shaped catalytic tunnel, whose innermost part is located in front of the, flavin ring. To provide insight into the PAO substrate specificity and, amine oxidation mechanism, we have investigated the crystal structure of, maize PAO in the reduced state and in complex with three different, inhibitors, guazatine, 1,8-diaminooctane, and, N(1)-ethyl-N(11)-[(cycloheptyl)methyl]-4,8-diazaundecane (CHENSpm). In the, reduced state, the conformation of the isoalloxazine ring and the, surrounding residues is identical to that of the oxidized enzyme. Only, Lys300 moves away from the flavin to compensate for the change in cofactor, protonation occurring upon reduction. The structure of the PAO.inhibitor, complexes reveals an exact match between the inhibitors and the PAO, catalytic tunnel. Inhibitor binding does not involve any protein, conformational change. Such lock-and-key binding occurs also in the, complex with CHENSpm, which forms a covalent adduct with the flavin N5, atom. Comparison of the enzyme complexes hints at an "out-of-register", mechanism of inhibition, in which the inhibitor secondary amino groups are, not properly aligned with respect to the flavin to allow oxidation. Except, for the Glu62-Glu170 pair, no negatively charged residues are involved in, the recognition of substrate and inhibitor amino groups, which is in, contrast to other polyamine binding proteins. This feature may be, exploited in the design of drugs specifically targeting PAO.
About this Structure
1H86 is a Single protein structure of sequence from Zea mays with and as ligands. Active as Polyamine oxidase, with EC number 1.5.3.11 Known structural/functional Sites: , , , , and . Full crystallographic information is available from OCA.
Reference
Structural bases for inhibitor binding and catalysis in polyamine oxidase., Binda C, Angelini R, Federico R, Ascenzi P, Mattevi A, Biochemistry. 2001 Mar 6;40(9):2766-76. PMID:11258887
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