2vrl
From Proteopedia
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'''STRUCTURE OF HUMAN MAO B IN COMPLEX WITH BENZYLHYDRAZINE''' | '''STRUCTURE OF HUMAN MAO B IN COMPLEX WITH BENZYLHYDRAZINE''' | ||
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| + | ==Overview== | ||
| + | The structure and mechanism of human monoamine oxidase B (MAO B) inhibition by hydrazines are investigated and compared with data on human monoamine oxidase A (MAO A). The inhibition properties of phenylethylhydrazine, benzylhydrazine, and phenylhydrazine are compared for both enzymes. Benzylhydrazine is bound more tightly to MAO B than to MAO A, and phenylhydrazine is bound weakly by either enzyme. Phenylethylhydrazine stoichiometrically reduces the covalent FAD moieties of MAO A and of MAO B. Molecular oxygen is required for the inhibition reactions, and the level of O 2 consumption for phenylethylhydrazine is 6-7-fold higher with either MAO A or MAO B than for the corresponding reactions with benzylhydrazine or phenylhydrazine. Mass spectral analysis of either inhibited enzyme shows the major product is a single covalent addition of the hydrazine arylalkyl group, although lower levels of dialkylated species are detected. Absorption and mass spectral data of the inhibited enzymes show that the FAD is the major site of alkylation. The three-dimensional (2.3 A) structures of phenylethylhydrazine- and benzylhydrazine-inhibited MAO B show that alkylation occurs at the N(5) position on the re face of the covalent flavin with loss of the hydrazyl nitrogens. A mechanistic scheme is proposed to account for these data, which involves enzyme-catalyzed conversion of the hydrazine to the diazene. From literature data on the reactivities of diazenes, O 2 then reacts with the bound diazene to form an alkyl radical, N 2 and superoxide anion. The bound arylalkyl radical reacts with the N(5) of the flavin, while the dissociated diazene reacts nonspecifically with the enzyme through arylalkylradicals. | ||
==About this Structure== | ==About this Structure== | ||
2VRL 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=2VRL OCA]. | 2VRL 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=2VRL OCA]. | ||
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| + | ==Reference== | ||
| + | Structural and Mechanistic Studies of Arylalkylhydrazine Inhibition of Human Monoamine Oxidases A and B., Binda C, Wang J, Li M, Hubalek F, Mattevi A, Edmondson DE, Biochemistry. 2008 Apr 22;. PMID:[http://www.ncbi.nlm.nih.gov/pubmed/18426226 18426226] | ||
[[Category: Homo sapiens]] | [[Category: Homo sapiens]] | ||
[[Category: Single protein]] | [[Category: Single protein]] | ||
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[[Category: Oxidoreductase]] | [[Category: Oxidoreductase]] | ||
[[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 Wed May 7 08:54:46 2008'' |
Revision as of 05:55, 7 May 2008
STRUCTURE OF HUMAN MAO B IN COMPLEX WITH BENZYLHYDRAZINE
Overview
The structure and mechanism of human monoamine oxidase B (MAO B) inhibition by hydrazines are investigated and compared with data on human monoamine oxidase A (MAO A). The inhibition properties of phenylethylhydrazine, benzylhydrazine, and phenylhydrazine are compared for both enzymes. Benzylhydrazine is bound more tightly to MAO B than to MAO A, and phenylhydrazine is bound weakly by either enzyme. Phenylethylhydrazine stoichiometrically reduces the covalent FAD moieties of MAO A and of MAO B. Molecular oxygen is required for the inhibition reactions, and the level of O 2 consumption for phenylethylhydrazine is 6-7-fold higher with either MAO A or MAO B than for the corresponding reactions with benzylhydrazine or phenylhydrazine. Mass spectral analysis of either inhibited enzyme shows the major product is a single covalent addition of the hydrazine arylalkyl group, although lower levels of dialkylated species are detected. Absorption and mass spectral data of the inhibited enzymes show that the FAD is the major site of alkylation. The three-dimensional (2.3 A) structures of phenylethylhydrazine- and benzylhydrazine-inhibited MAO B show that alkylation occurs at the N(5) position on the re face of the covalent flavin with loss of the hydrazyl nitrogens. A mechanistic scheme is proposed to account for these data, which involves enzyme-catalyzed conversion of the hydrazine to the diazene. From literature data on the reactivities of diazenes, O 2 then reacts with the bound diazene to form an alkyl radical, N 2 and superoxide anion. The bound arylalkyl radical reacts with the N(5) of the flavin, while the dissociated diazene reacts nonspecifically with the enzyme through arylalkylradicals.
About this Structure
2VRL is a Single protein structure of sequence from Homo sapiens. Full crystallographic information is available from OCA.
Reference
Structural and Mechanistic Studies of Arylalkylhydrazine Inhibition of Human Monoamine Oxidases A and B., Binda C, Wang J, Li M, Hubalek F, Mattevi A, Edmondson DE, Biochemistry. 2008 Apr 22;. PMID:18426226 Page seeded by OCA on Wed May 7 08:54:46 2008
Categories: Homo sapiens | Single protein | Binda, C. | Edmondson, D E. | Hubalek, F. | Li, M. | Mattevi, A. | Wang, J. | Acetylation | Fad | Flavin | Flavoprotein | Hydrazine | Inhibitor binding | Membrane | Membrane protein | Mitochondrion | Monoamine oxidase | Oxidoreductase | Transmembrane
