English (United Kingdom)

https://curated-unify.zendy.io/wp-json/zendy-region/v1/featured_content/oa?rat=en

https://curated-unify.zendy.io/wp-json/zendy-region/v1/highlighted_journal/

Zendy Pro

Presents the zaia usage as premium feature

ZAIA

Presents AI Discovery search usage as a premium feature

AI Discovery

Presents AI Discovery explain and summary usage as a premium feature

Content Analysis

Presents the keyphrase highlighting as premium feature

Keyphrase Highlighting

Presents the summarisation as premium feature

Summarisation

Presents the pdf analysis as premium feature

PDF Analysis

1500 Top-up

3000 Top-up

Zendy Basic

2500 Top-up

Zendy Unlimited

Presents the access of premium content as premium feature

Premium Content

The mitochondrial outer membrane Monoamine Oxidases A and B (MAO A and MAO B) have been targets for neuro-protective drug research over the past 40 years since they are part of the catabolism of neurotransmitters such as serotonin and dopamine. Structure determination of either enzyme has been precluded mainly due to their membrane-association. In the past year, we have solved the structure of human MAO B by multicrystal averaging based on two crystal forms grown from different detergents. This is one of the first structures of a monotopically inserted membrane protein to be completed. MAO-B structure shows the membrane interacting regions as a C-terminal transmembrane helix, plus apolar loops located at various positions in the sequence. The overall structure is a dimer, but does not involve helix-helix interactions within the membrane inserted segments. The structure was solved in complex with pargyline, which occupies the substrate binding site. A smaller 'entrance' cavity forms an entry way between the active site cavity and the protein surface. The amino acid residues separating these two cavities in MAO B differ in MAO A and mutagensis experiments targeting these residues on MAO B result in a enzyme with properties closer to MAO A than to MAO B. The opening of the entrance cavity is toward the membrane surface suggesting substrate access is from the membrane bilayer. MAO B structure rationalizes previous QSAR data and provides basic information for the rational design of drugs that would exhibit a high degree of specificity.

Structure of human monoamine oxidase B, a drug target for neurological disorders