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Structure of the sodium borohydride-reduced N-(cyclopropyl)glycine adduct of the flavoenzyme monomeric sarcosine oxidase
Journal article   Peer reviewed

Structure of the sodium borohydride-reduced N-(cyclopropyl)glycine adduct of the flavoenzyme monomeric sarcosine oxidase

Zhi-wei Chen, Gouhua Zhao, Suzana Martinovic, Marilyn Schuman Jorns and F Scott Mathews
Biochemistry (Easton), v 44(47), pp 15444-15450
29 Nov 2005
DOI: https://doi.org/10.1021/bi0515422
PMID: 16300392
Featured in Collection :   UN Sustainable Development Goals @ Drexel

Abstract

Flavin-Adenine Dinucleotide - chemistry Glycine - analogs & derivatives Electron Transport Borohydrides - chemistry Glycine - chemistry Oxidation-Reduction Crystallography, X-Ray Molecular Structure Peptides, Cyclic - chemistry Sarcosine Oxidase - chemistry
Monomeric sarcosine oxidase (MSOX) is a flavoprotein that contains covalently bound FAD [8a-(S-cysteinyl)FAD] and catalyzes the oxidation of sarcosine (N-methylglycine) and other secondary amino acids, such as l-proline. Our previous studies showed that N-(cyclopropyl)glycine (CPG) acts as a mechanism-based inactivator of MSOX [Zhao, G., et al. (2000) Biochemistry 39, 14341-14347]. The reaction results in the formation of a modified reduced flavin that can be further reduced and stabilized by treatment with sodium borohydride. The borohydride-reduced CPG-modified enzyme exhibits a mass increase of 63 +/- 2 Da as compared with native MSOX. The crystal structure of the modified enzyme, solved at 1.85 A resolution, shows that FAD is the only site of modification. The modified FAD contains a fused five-membered ring, linking the C(4a) and N(5) atoms of the flavin ring, with an additional oxygen atom bound to the carbon atom attached to N(5) and a tetrahedral carbon atom at flavin C(4) with a hydroxyl group attached to C(4). On the basis of the crystal structure of the borohydride-stabilized adduct, we conclude that the labile CPG-modified flavin is a 4a,5-dihydroflavin derivative with a substituent derived from the cleavage of the cyclopropyl ring in CPG. The results are consistent with CPG-mediated inactivation in a reaction initiated by single electron transfer from the amine function in CPG to FAD in MSOX, followed by collapse of the radical pair to yield a covalently modified 4a,5-dihydroflavin.

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Domestic collaboration
Web of Science research areas
Biochemistry & Molecular Biology
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