2bk4
From Proteopedia
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|PDB= 2bk4 |SIZE=350|CAPTION= <scene name='initialview01'>2bk4</scene>, resolution 1.90Å | |PDB= 2bk4 |SIZE=350|CAPTION= <scene name='initialview01'>2bk4</scene>, resolution 1.90Å | ||
|SITE= <scene name='pdbsite=AC1:Rsa+Binding+Site+For+Chain+B'>AC1</scene> | |SITE= <scene name='pdbsite=AC1:Rsa+Binding+Site+For+Chain+B'>AC1</scene> | ||
| - | |LIGAND= <scene name='pdbligand=FAD:FLAVIN-ADENINE DINUCLEOTIDE'>FAD</scene> | + | |LIGAND= <scene name='pdbligand=FAD:FLAVIN-ADENINE+DINUCLEOTIDE'>FAD</scene>, <scene name='pdbligand=RAS:N-PROPARGYL-1(R)-AMINONDAN'>RAS</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] | + | |ACTIVITY= <span class='plainlinks'>[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] </span> |
|GENE= | |GENE= | ||
| + | |DOMAIN= | ||
| + | |RELATEDENTRY= | ||
| + | |RESOURCES=<span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2bk4 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2bk4 OCA], [http://www.ebi.ac.uk/pdbsum/2bk4 PDBsum], [http://www.rcsb.org/pdb/explore.do?structureId=2bk4 RCSB]</span> | ||
}} | }} | ||
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[[Category: Li, M.]] | [[Category: Li, M.]] | ||
[[Category: Mattevi, A.]] | [[Category: Mattevi, A.]] | ||
| - | [[Category: FAD]] | ||
[[Category: fad]] | [[Category: fad]] | ||
[[Category: fad-containing amine oxidase]] | [[Category: fad-containing amine oxidase]] | ||
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[[Category: transmembrane]] | [[Category: transmembrane]] | ||
| - | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Mon Mar 31 02:07:34 2008'' |
Revision as of 23:07, 30 March 2008
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| , resolution 1.90Å | |||||||
|---|---|---|---|---|---|---|---|
| Sites: | |||||||
| Ligands: | , | ||||||
| Activity: | Amine oxidase (flavin-containing), with EC number 1.4.3.4 | ||||||
| Resources: | FirstGlance, OCA, PDBsum, RCSB | ||||||
| Coordinates: | save as pdb, mmCIF, xml | ||||||
HUMAN MONOAMINE OXIDASE B: I199F MUTANT IN COMPLEX WITH RASAGILINE
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
2BK4 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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