Logo Medical Science Monitor

Call: +1.631.470.9640
Mon - Fri 10:00 am - 02:00 pm EST

Contact Us

Logo Medical Science Monitor Logo Medical Science Monitor Logo Medical Science Monitor

01 September 2005

Alteration in spectral properties on ligand binding reveals flexibility inmonoamine oxidase.

Rona R Ramsay, Tadeusz Z.E. Jones, Robert M.G. Hynson

Med Sci Monit 2005; 11(9): SR15-20 :: ID: 428462

Abstract

Crystal structures have opened the door to understanding the mechanismand ligand specificities of MAO A and MAO B. We review here functional properties that suggest a flexibilityin MAO that is likely to influence catalysis under different cellular conditions. The flexibility indicatedby altered oxidation kinetics and a changed redox potential in the presence of a substrate was confirmedby circular dichroism spectroscopy. Circular dichroism also demonstrated alterations in the conformationof aromatic residues during reduction of MAO A and after covalent modification of the flavin. Visiblespectra provide a convenient way to monitor ligand binding in the active site. Different groups nearthe flavin give different spectral changes. During reduction of MAO A, a distinct 412 nm peak appearsafter partial reduction. Recent work suggests that this may be a tyrosyl radical in equilibrium withthe semiquinone of the flavin. Substrates prevent the appearance of the 412 nm peak but many inhibitorsenhance it by preventing further reduction. We propose that steric effects in the active site could bethe mechanism of this difference. Flexibility is also important for the transmission of the effects ofmodifying the surface thiols to the active site. Modification of multiple thiols results in inactivationbut mutation of a single thiol, cysteine 374 in MAO A to alanine, decreased the catalytic potency (kcat/Km)by 30%. Thus, surface modification of MAO (for example, by oxidative stress) could reduce its activity.

Keywords: Cysteine - chemistry, Catalytic Domain, Allosteric Regulation, Kinetics, Ligands, Models, Molecular, Monoamine Oxidase - metabolism, Monoamine Oxidase Inhibitors - pharmacology, Oxidation-Reduction, Protein Conformation

Add Comment 0 Comments

Editorial

01 March 2024 : Editorial  

Editorial: First Regulatory Approvals for CRISPR-Cas9 Therapeutic Gene Editing for Sickle Cell Disease and Transfusion-Dependent β-Thalassemia

Dinah V. Parums

DOI: 10.12659/MSM.944204

Med Sci Monit 2024; 30:e944204

0:00

In Press

18 Mar 2024 : Clinical Research  

Sexual Dysfunction in Women After Tibial Fracture: A Retrospective Comparative Study

Med Sci Monit In Press; DOI: 10.12659/MSM.944136  

0:00

21 Feb 2024 : Clinical Research  

Potential Value of HSP90α in Prognosis of Triple-Negative Breast Cancer

Med Sci Monit In Press; DOI: 10.12659/MSM.943049  

22 Feb 2024 : Review article  

Differentiation of Native Vertebral Osteomyelitis: A Comprehensive Review of Imaging Techniques and Future ...

Med Sci Monit In Press; DOI: 10.12659/MSM.943168  

23 Feb 2024 : Clinical Research  

A Study of 60 Patients with Low Back Pain to Compare Outcomes Following Magnetotherapy, Ultrasound, Laser, ...

Med Sci Monit In Press; DOI: 10.12659/MSM.943732  

Most Viewed Current Articles

16 May 2023 : Clinical Research  

Electrophysiological Testing for an Auditory Processing Disorder and Reading Performance in 54 School Stude...

DOI :10.12659/MSM.940387

Med Sci Monit 2023; 29:e940387

0:00

17 Jan 2024 : Review article  

Vaccination Guidelines for Pregnant Women: Addressing COVID-19 and the Omicron Variant

DOI :10.12659/MSM.942799

Med Sci Monit 2024; 30:e942799

0:00

14 Dec 2022 : Clinical Research  

Prevalence and Variability of Allergen-Specific Immunoglobulin E in Patients with Elevated Tryptase Levels

DOI :10.12659/MSM.937990

Med Sci Monit 2022; 28:e937990

0:00

01 Jan 2022 : Editorial  

Editorial: Current Status of Oral Antiviral Drug Treatments for SARS-CoV-2 Infection in Non-Hospitalized Pa...

DOI :10.12659/MSM.935952

Med Sci Monit 2022; 28:e935952

0:00

Your Privacy

We use cookies to ensure the functionality of our website, to personalize content and advertising, to provide social media features, and to analyze our traffic. If you allow us to do so, we also inform our social media, advertising and analysis partners about your use of our website, You can decise for yourself which categories you you want to deny or allow. Please note that based on your settings not all functionalities of the site are available. View our privacy policy.

Medical Science Monitor eISSN: 1643-3750
Medical Science Monitor eISSN: 1643-3750