1s2y: Difference between revisions
New page: left|200px<br /> <applet load="1s2y" size="450" color="white" frame="true" align="right" spinBox="true" caption="1s2y, resolution 2.12Å" /> '''Crystal structure o... |
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[[Image:1s2y.gif|left|200px]]<br /> | [[Image:1s2y.gif|left|200px]]<br /><applet load="1s2y" size="350" color="white" frame="true" align="right" spinBox="true" | ||
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caption="1s2y, resolution 2.12Å" /> | caption="1s2y, resolution 2.12Å" /> | ||
'''Crystal structure of MAOB in complex with N-propargyl-1(S)-aminoindan'''<br /> | '''Crystal structure of MAOB in complex with N-propargyl-1(S)-aminoindan'''<br /> | ||
==Overview== | ==Overview== | ||
Monoamine oxidase B (MAO B) is an outer mitochondrial membrane enzyme that | Monoamine oxidase B (MAO B) is an outer mitochondrial membrane enzyme that catalyzes the oxidation of arylalkylamine neurotransmitters. The crystal structures of MAO B in complex with four of the N-propargylaminoindan class of MAO covalent inhibitors (rasagiline, N-propargyl-1(S)-aminoindan, 6-hydroxy-N-propargyl-1(R)-aminoindan, and N-methyl-N-propargyl-1(R)-aminoindan) have been determined at a resolution of better than 2.1 A. Rasagiline, 6-hydroxy-N-propargyl-1(R)-aminoindan, and N-methyl-N-propargyl-1(R)-aminoindan adopt essentially the same conformation with the extended propargyl chain covalently bound to the flavin and the indan ring located in the rear of the substrate cavity. N-Propargyl-1(S)-aminoindan binds with the indan ring in a flipped conformation with respect to the other inhibitors, which causes a slight movement of the Tyr326 side chain. Four ordered water molecules are an integral part of the active site and establish H-bond interactions to the inhibitor atoms. These structural studies may guide future drug design to improve selectivity and efficacy by introducing appropriate substituents on the rasagiline molecular scaffold. | ||
==About this Structure== | ==About this Structure== | ||
1S2Y is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] with FAD as [http://en.wikipedia.org/wiki/ligand ligand]. Active as [http://en.wikipedia.org/wiki/Amine_oxidase_(flavin-containing) Amine oxidase (flavin-containing)], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=1.4.3.4 1.4.3.4] Full crystallographic information is available from [http:// | 1S2Y is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] with <scene name='pdbligand=FAD:'>FAD</scene> as [http://en.wikipedia.org/wiki/ligand ligand]. Active as [http://en.wikipedia.org/wiki/Amine_oxidase_(flavin-containing) Amine oxidase (flavin-containing)], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=1.4.3.4 1.4.3.4] Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1S2Y OCA]. | ||
==Reference== | ==Reference== | ||
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[[Category: Single protein]] | [[Category: Single protein]] | ||
[[Category: Binda, C.]] | [[Category: Binda, C.]] | ||
[[Category: Edmondson, D | [[Category: Edmondson, D E.]] | ||
[[Category: Herzig, Y.]] | [[Category: Herzig, Y.]] | ||
[[Category: Hubalek, F.]] | [[Category: Hubalek, F.]] | ||
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[[Category: rasagiline]] | [[Category: rasagiline]] | ||
''Page seeded by [http:// | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 14:57:19 2008'' | ||
Revision as of 15:57, 21 February 2008
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Crystal structure of MAOB in complex with N-propargyl-1(S)-aminoindan
OverviewOverview
Monoamine oxidase B (MAO B) is an outer mitochondrial membrane enzyme that catalyzes the oxidation of arylalkylamine neurotransmitters. The crystal structures of MAO B in complex with four of the N-propargylaminoindan class of MAO covalent inhibitors (rasagiline, N-propargyl-1(S)-aminoindan, 6-hydroxy-N-propargyl-1(R)-aminoindan, and N-methyl-N-propargyl-1(R)-aminoindan) have been determined at a resolution of better than 2.1 A. Rasagiline, 6-hydroxy-N-propargyl-1(R)-aminoindan, and N-methyl-N-propargyl-1(R)-aminoindan adopt essentially the same conformation with the extended propargyl chain covalently bound to the flavin and the indan ring located in the rear of the substrate cavity. N-Propargyl-1(S)-aminoindan binds with the indan ring in a flipped conformation with respect to the other inhibitors, which causes a slight movement of the Tyr326 side chain. Four ordered water molecules are an integral part of the active site and establish H-bond interactions to the inhibitor atoms. These structural studies may guide future drug design to improve selectivity and efficacy by introducing appropriate substituents on the rasagiline molecular scaffold.
About this StructureAbout this Structure
1S2Y is a Single protein structure of sequence from Homo sapiens with as ligand. Active as Amine oxidase (flavin-containing), with EC number 1.4.3.4 Full crystallographic information is available from OCA.
ReferenceReference
Crystal structures of monoamine oxidase B in complex with four inhibitors of the N-propargylaminoindan class., Binda C, Hubalek F, Li M, Herzig Y, Sterling J, Edmondson DE, Mattevi A, J Med Chem. 2004 Mar 25;47(7):1767-74. PMID:15027868
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