This old version of Proteopedia is provided for student assignments while the new version is undergoing repairs. Content and edits done in this old version of Proteopedia after March 1, 2026 will eventually be lost when it is retired in about June of 2026.
Apply for new accounts at the new Proteopedia. Your logins will work in both the old and new versions.
1ojc
From Proteopedia
| Line 1: | Line 1: | ||
| - | [[Image:1ojc.gif|left|200px]] | + | [[Image:1ojc.gif|left|200px]] |
| - | + | ||
| - | '''HUMAN MONOAMINE OXIDASE B IN COMPLEX WITH N-(2-AMINOETHYL)-P-CHLOROBENZAMIDE''' | + | {{Structure |
| + | |PDB= 1ojc |SIZE=350|CAPTION= <scene name='initialview01'>1ojc</scene>, resolution 2.40Å | ||
| + | |SITE= <scene name='pdbsite=AC1:Laz+Binding+Site+For+Chain+B'>AC1</scene> | ||
| + | |LIGAND= <scene name='pdbligand=FAD:FLAVIN-ADENINE DINUCLEOTIDE'>FAD</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 N-(2-AMINOETHYL)-P-CHLOROBENZAMIDE''' | ||
| + | |||
==Overview== | ==Overview== | ||
| Line 7: | Line 16: | ||
==About this Structure== | ==About this Structure== | ||
| - | 1OJC is a [ | + | 1OJC 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=1OJC 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]] | ||
| Line 22: | Line 31: | ||
[[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 13:11:41 2008'' |
Revision as of 11:11, 20 March 2008
| |||||||
| , resolution 2.40Å | |||||||
|---|---|---|---|---|---|---|---|
| Sites: | |||||||
| Ligands: | |||||||
| 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 N-(2-AMINOETHYL)-P-CHLOROBENZAMIDE
Overview
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 Structure
1OJC is a Single protein structure of sequence from Homo sapiens. Full crystallographic information is available from OCA.
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:12913124
Page seeded by OCA on Thu Mar 20 13:11:41 2008
