1oj9: Difference between revisions
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[[Image:1oj9.gif|left|200px]] | [[Image:1oj9.gif|left|200px]] | ||
'''HUMAN MONOAMINE OXIDASE B IN COMPLEX WITH 1,4-DIPHENYL-2-BUTENE''' | {{Structure | ||
|PDB= 1oj9 |SIZE=350|CAPTION= <scene name='initialview01'>1oj9</scene>, resolution 2.3Å | |||
|SITE= <scene name='pdbsite=AC1:1pb+Binding+Site+For+Chain+B'>AC1</scene> | |||
|LIGAND= <scene name='pdbligand=FAD:FLAVIN-ADENINE+DINUCLEOTIDE'>FAD</scene> and <scene name='pdbligand=1PB:1,4-DIPHENYL-2-BUTENE'>1PB</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 IN COMPLEX WITH 1,4-DIPHENYL-2-BUTENE''' | |||
==Overview== | ==Overview== | ||
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==About this Structure== | ==About this Structure== | ||
1OJ9 is a [ | 1OJ9 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=1OJ9 OCA]. | ||
==Reference== | ==Reference== | ||
Insights into the mode of inhibition of human mitochondrial monoamine oxidase B from high-resolution crystal structures., Binda C, Li M, Hubalek F, Restelli N, Edmondson DE, Mattevi A, Proc Natl Acad Sci U S A. 2003 Aug 19;100(17):9750-5. Epub 2003 Aug 11. PMID:[http:// | Insights into the mode of inhibition of human mitochondrial monoamine oxidase B from high-resolution crystal structures., Binda C, Li M, Hubalek F, Restelli N, Edmondson DE, Mattevi A, Proc Natl Acad Sci U S A. 2003 Aug 19;100(17):9750-5. Epub 2003 Aug 11. PMID:[http://www.ncbi.nlm.nih.gov/pubmed/12913124 12913124] | ||
[[Category: Amine oxidase (flavin-containing)]] | [[Category: Amine oxidase (flavin-containing)]] | ||
[[Category: Homo sapiens]] | [[Category: Homo sapiens]] | ||
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[[Category: oxidoreductase]] | [[Category: oxidoreductase]] | ||
''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 13:11:42 2008'' | ||
Revision as of 14:11, 20 March 2008
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| , resolution 2.3Å | |||||||
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| Sites: | |||||||
| Ligands: | and | ||||||
| Activity: | Amine oxidase (flavin-containing), with EC number 1.4.3.4 | ||||||
| Coordinates: | save as pdb, mmCIF, xml | ||||||
HUMAN MONOAMINE OXIDASE B IN COMPLEX WITH 1,4-DIPHENYL-2-BUTENE
OverviewOverview
Monoamine oxidase B (MAO-B) is an outer mitochondrial membrane-bound enzyme that catalyzes the oxidative deamination of arylalkylamine neurotransmitters and has been a target for a number of clinically used drug inhibitors. The 1.7-A structure of the reversible isatin-MAO-B complex has been determined; it forms a basis for the interpretation of the enzyme's structure when bound to either reversible or irreversible inhibitors. 1,4-Diphenyl-2-butene is found to be a reversible MAO-B inhibitor, which occupies both the entrance and substrate cavity space in the enzyme. Comparison of these two structures identifies Ile-199 as a "gate" between the two cavities. Rotation of the side chain allows for either separation or fusion of the two cavities. Inhibition of the enzyme with N-(2-aminoethyl)-p-chlorobenzamide results in the formation of a covalent N(5) flavin adduct with the phenyl ring of the inhibitor occupying a position in the catalytic site overlapping that of isatin. Inhibition of MAO-B with the clinically used trans-2-phenylcyclopropylamine results in the formation of a covalent C(4a) flavin adduct with an opened cyclopropyl ring and the phenyl ring in a parallel orientation to the flavin. The peptide bond between the flavin-substituted Cys-397 and Tyr-398 is in a cis conformation, which allows the proper orientation of the phenolic ring of Tyr-398 in the active site. The flavin ring exists in a twisted nonplanar conformation, which is observed in the oxidized form as well as in both the N(5) and the C(4a) adducts. An immobile water molecule is H-bonded to Lys-296 and to the N(5) of the flavin as observed in other flavin-dependent amine oxidases. The active site cavities are highly apolar; however, hydrophilic areas exist near the flavin and direct the amine moiety of the substrate for binding and catalysis. Small conformational changes are observed on comparison of the different inhibitor-enzyme complexes. Future MAO-B drug design will need to consider "induced fit" contributions as an element in ligand-enzyme interactions.
About this StructureAbout this Structure
1OJ9 is a Single protein structure of sequence from Homo sapiens. Full crystallographic information is available from OCA.
ReferenceReference
Insights into the mode of inhibition of human mitochondrial monoamine oxidase B from high-resolution crystal structures., Binda C, Li M, Hubalek F, Restelli N, Edmondson DE, Mattevi A, Proc Natl Acad Sci U S A. 2003 Aug 19;100(17):9750-5. Epub 2003 Aug 11. PMID:12913124
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