'''HUMAN MONOAMINE OXIDASE B IN COMPLEX WITH LAURYLDIMETHYLAMINE-N-OXIDE (LDAO)'''
===HUMAN MONOAMINE OXIDASE B IN COMPLEX WITH LAURYLDIMETHYLAMINE-N-OXIDE (LDAO)===
==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.
The line below this paragraph, {{ABSTRACT_PUBMED_12913124}}, adds the Publication Abstract to the page
(as it appears on PubMed at http://www.pubmed.gov), where 12913124 is the PubMed ID number.
-->
{{ABSTRACT_PUBMED_12913124}}
==About this Structure==
==About this Structure==
Line 28:
Line 32:
[[Category: Maob]]
[[Category: Maob]]
[[Category: Oxidoreductase]]
[[Category: Oxidoreductase]]
''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sat May 3 03:55:21 2008''
''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Mon Jul 28 06:05:52 2008''
Revision as of 06:05, 28 July 2008
This article has been automatically seeded. Changes to this page should pertain to the PDB entry only and not to the protein or biomolecule in general.
HUMAN MONOAMINE OXIDASE B IN COMPLEX WITH LAURYLDIMETHYLAMINE-N-OXIDE (LDAO)HUMAN MONOAMINE OXIDASE B IN COMPLEX WITH LAURYLDIMETHYLAMINE-N-OXIDE (LDAO)
1OJD 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
