Journal article
Inactivation of Monomeric Sarcosine Oxidase by Reaction with N-(Cyclopropyl)glycine
Biochemistry (Easton), v 39(46), pp 14341-14347
21 Nov 2000
PMID: 11087383
Featured in Collection : UN Sustainable Development Goals @ Drexel
Abstract
Monomeric sarcosine oxidase (MSOX) catalyzes the oxidative demethylation of sarcosine (N-methylglycine) and contains covalently bound flavin adenine dinucleotide (FAD). The present study demonstrates that N-(cyclopropyl)glycine (CPG) is a mechanism-based inhibitor. CPG forms a charge transfer complex with MSOX that reacts under aerobic conditions to yield a covalently modified, reduced flavin (λmax = 422 nm, ε422 = 3.9 mM-1 cm-1), accompanied by a loss of enzyme activity. The CPG-modified flavin is converted at an 8-fold slower rate to 1,5-dihydro-FAD (EFADH2), which reacts rapidly with oxygen to regenerate unmodified, oxidized enzyme. As a result, CPG-modified MSOX reaches a CPG-dependent steady-state concentration under aerobic conditions and reverts back to unmodified enzyme upon removal of excess reagent. No loss of activity is observed under anaerobic conditions where EFADH2 is formed in a reaction that goes to completion at low CPG concentrations. Aerobic denaturation of CPG-modified enzyme yields unmodified, oxidized flavin at a rate similar to the anaerobic denaturation reaction, which yields 1,5-dihydro-FAD. The CPG-modified flavin can be reduced with borohydride, a reaction that blocks conversion to unmodified flavin upon removal of excess CPG or enzyme denaturation. The possible chemical mechanism of inactivation and structure of the CPG-modified flavin are discussed.
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Details
- Title
- Inactivation of Monomeric Sarcosine Oxidase by Reaction with N-(Cyclopropyl)glycine
- Creators
- Gouhua Zhao - Hahnemann University HospitalJunya Qu - Temple UniversityFranklin A Davis - Temple UniversityMarilyn Schuman Jorns (Corresponding Author) - Hahnemann University Hospital
- Publication Details
- Biochemistry (Easton), v 39(46), pp 14341-14347
- Publisher
- American Chemical Society; Washington, DC
- Resource Type
- Journal article
- Language
- English
- Academic Unit
- Biochemistry and Molecular Biology; [Retired Faculty]
- Web of Science ID
- WOS:000165355700037
- Scopus ID
- 2-s2.0-0034700319
- Other Identifier
- 991014878291904721
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- Collaboration types
- Domestic collaboration
- Web of Science research areas
- Biochemistry & Molecular Biology