2bk5
From Proteopedia
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| - | [[Image:2bk5.gif|left|200px]] | + | [[Image:2bk5.gif|left|200px]] |
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| - | '''HUMAN MONOAMINE OXIDASE B: I199F MUTANT IN COMPLEX WITH ISATIN''' | + | {{Structure |
| + | |PDB= 2bk5 |SIZE=350|CAPTION= <scene name='initialview01'>2bk5</scene>, resolution 1.83Å | ||
| + | |SITE= <scene name='pdbsite=AC1:Binding+Site+For+Residue+Fad+A+600'>AC1</scene>, <scene name='pdbsite=AC2:Binding+Site+For+Residue+Isn+A+601'>AC2</scene>, <scene name='pdbsite=AC3:Binding+Site+For+Residue+Fad+B+600'>AC3</scene> and <scene name='pdbsite=AC4:Binding+Site+For+Residue+Isn+B+601'>AC4</scene> | ||
| + | |LIGAND= <scene name='pdbligand=FAD:FLAVIN-ADENINE+DINUCLEOTIDE'>FAD</scene> and <scene name='pdbligand=ISN:ISATIN'>ISN</scene> | ||
| + | |ACTIVITY= [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] | ||
| + | |GENE= | ||
| + | }} | ||
| + | |||
| + | '''HUMAN MONOAMINE OXIDASE B: I199F MUTANT IN COMPLEX WITH ISATIN''' | ||
| + | |||
==Overview== | ==Overview== | ||
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==About this Structure== | ==About this Structure== | ||
| - | 2BK5 is a [ | + | 2BK5 is a [[Single protein]] structure of 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=2BK5 OCA]. |
==Reference== | ==Reference== | ||
| - | Demonstration of isoleucine 199 as a structural determinant for the selective inhibition of human monoamine oxidase B by specific reversible inhibitors., Hubalek F, Binda C, Khalil A, Li M, Mattevi A, Castagnoli N, Edmondson DE, J Biol Chem. 2005 Apr 22;280(16):15761-6. Epub 2005 Feb 14. PMID:[http:// | + | Demonstration of isoleucine 199 as a structural determinant for the selective inhibition of human monoamine oxidase B by specific reversible inhibitors., Hubalek F, Binda C, Khalil A, Li M, Mattevi A, Castagnoli N, Edmondson DE, J Biol Chem. 2005 Apr 22;280(16):15761-6. Epub 2005 Feb 14. PMID:[http://www.ncbi.nlm.nih.gov/pubmed/15710600 15710600] |
[[Category: Amine oxidase (flavin-containing)]] | [[Category: Amine oxidase (flavin-containing)]] | ||
[[Category: Homo sapiens]] | [[Category: Homo sapiens]] | ||
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[[Category: transmembrane]] | [[Category: transmembrane]] | ||
| - | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Mar 20 16:03:02 2008'' |
Revision as of 14:03, 20 March 2008
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| , resolution 1.83Å | |||||||
|---|---|---|---|---|---|---|---|
| Sites: | , , and | ||||||
| Ligands: | and | ||||||
| Activity: | Amine oxidase (flavin-containing), with EC number 1.4.3.4 | ||||||
| Coordinates: | save as pdb, mmCIF, xml | ||||||
HUMAN MONOAMINE OXIDASE B: I199F MUTANT IN COMPLEX WITH ISATIN
Overview
Several reversible inhibitors selective for human monoamine oxidase B (MAO B) that do not inhibit MAO A have been described in the literature. The following compounds: 8-(3-chlorostyryl)caffeine, 1,4-diphenyl-2-butene, and trans,trans-farnesol are shown to inhibit competitively human, horse, rat, and mouse MAO B with K(i) values in the low micromolar range but are without effect on either bovine or sheep MAO B or human MAO A. In contrast, the reversible competitive inhibitor isatin binds to all known MAO B and MAO A with similar affinities. Sequence alignments and the crystal structures of human MAO B in complex with 1,4-diphenyl-2-butene or with trans,trans-farnesol provide molecular insights into these specificities. These inhibitors span the substrate and entrance cavities with the side chain of Ile-199 rotated out of its normal conformation suggesting that Ile-199 is gating the substrate cavity. Ile-199 is conserved in all known MAO B sequences except bovine MAO B, which has Phe in this position (the sequence of sheep MAO B is unknown). Phe is conserved in the analogous position in MAO A sequences. The human MAO B I199F mutant protein of MAO B binds to isatin (K(i) = 3 microM) but not to the three inhibitors listed above. The crystal structure of this mutant demonstrates that the side chain of Phe-199 interferes with the binding of those compounds. This suggests that the Ile-199 "gate" is a determinant for the specificity of these MAO B inhibitors and provides a molecular basis for the development of MAO B-specific reversible inhibitors without interference with MAO A function in neurotransmitter metabolism.
About this Structure
2BK5 is a Single protein structure of sequence from Homo sapiens. Full crystallographic information is available from OCA.
Reference
Demonstration of isoleucine 199 as a structural determinant for the selective inhibition of human monoamine oxidase B by specific reversible inhibitors., Hubalek F, Binda C, Khalil A, Li M, Mattevi A, Castagnoli N, Edmondson DE, J Biol Chem. 2005 Apr 22;280(16):15761-6. Epub 2005 Feb 14. PMID:15710600
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