2z5y

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{{STRUCTURE_2z5y| PDB=2z5y | SCENE= }}
{{STRUCTURE_2z5y| PDB=2z5y | SCENE= }}
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'''Crystal Structure of Human Monoamine Oxidase A (G110A) with Harmine'''
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===Crystal Structure of Human Monoamine Oxidase A (G110A) with Harmine===
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==Overview==
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The mitochondrial outer membrane-anchored monoamine oxidase (MAO) is a biochemically important flavoenzyme that catalyzes the deamination of biogenic and xenobiotic amines. Its two subtypes, MAOA and MAOB, are linked to several psychiatric disorders and therefore are interesting targets for drug design. To understand the relationship between structure and function of this enzyme, we extended our previous low-resolution rat MAOA structure to the high-resolution wild-type and G110A mutant human MAOA structures at 2.2 and 2.17 A, respectively. The high-resolution MAOA structures are similar to those of rat MAOA and human MAOB, but different from the known structure of human MAOA [De Colibus L, et al. (2005) Proc Natl Acad Sci USA 102:12684-12689], specifically regarding residues 108-118 and 210-216, which surround the substrate/inhibitor cavity. The results confirm that the inhibitor selectivity of MAOA and MAOB is caused by the structural differences arising from Ile-335 in MAOA vs. Tyr-326 in MAOB. The structures exhibit a C-terminal transmembrane helix with clear electron density, as is also seen in rat MAOA. Mutations on one residue of loop 108-118, G110, which is far from the active center but close to the membrane surface, cause the solubilized enzyme to undergo a dramatic drop in activity, but have less effect when the enzyme is anchored in the membrane. These results suggest that the flexibility of loop 108-118, facilitated by anchoring the enzyme into the membrane, is essential for controlling substrate access to the active site. We report on the observation of the structure-function relationship between a transmembrane helical anchor and an extra-membrane domain.
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(as it appears on PubMed at http://www.pubmed.gov), where 18391214 is the PubMed ID number.
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{{ABSTRACT_PUBMED_18391214}}
==About this Structure==
==About this Structure==
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[[Category: Single helix trans-membrane protein]]
[[Category: Single helix trans-membrane protein]]
[[Category: Transmembrane]]
[[Category: Transmembrane]]
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Apr 24 09:31:33 2008''
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sun Jul 27 13:35:44 2008''

Revision as of 10:35, 27 July 2008

Template:STRUCTURE 2z5y

Crystal Structure of Human Monoamine Oxidase A (G110A) with Harmine

Template:ABSTRACT PUBMED 18391214

About this Structure

2Z5Y is a Single protein structure of sequence from Homo sapiens. Full crystallographic information is available from OCA.

Reference

Structure of human monoamine oxidase A at 2.2-A resolution: the control of opening the entry for substrates/inhibitors., Son SY, Ma J, Kondou Y, Yoshimura M, Yamashita E, Tsukihara T, Proc Natl Acad Sci U S A. 2008 Apr 15;105(15):5739-44. Epub 2008 Apr 7. PMID:18391214

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