Substrate recognition and activation mechanism of D-amino acid oxidase: a study using substrate analogs.

Substrate recognition and activation mechanism of D-amino acid oxidase: a study using substrate analogs. Research Abstract Details 

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Substrate recognition and activation mechanism of D-amino acid oxidase: a study using substrate analogs. Abstract Text:

Y Nishina,K Sato,R Miura,K Shiga,

We investigated the mechanism of recognition and activation of substrate by D-amino acid oxidase (DAO) by thermodynamical and spectrophotometric methods using zwitterionic ligands [N-methylisonicotinate (NMIN), trigonelline, and homarine] and monoanionic ligands as model compounds of the substrate and the product. In terms of the charge within the substrate D-amino acid, monoanionic (e.g., benzoate), zwitterionic (e.g., NMIN), and dianionic (e.g., terephthalate) ligands are thought to be good models for neutral, basic, and acidic amino acids, respectively, because when a substrate binds to DAO, as previously reported, the a-ammonium group (-NH(3)(+)) probably loses a proton to become neutral (-NH(2)) before the oxidation. Zwitterionic ligands can also be good model compounds of product in the purple complex (the complex of reduced DAO with the product imino acid), because the imino nitrogen of the imino acid is in a protonated cationic form. We also discuss electrostatic interaction, steric effect, and charge-transfer interaction as factors which affect the affinity of substrate/ligand for DAO. Monoanionic ligands have high affinity for neutral forms of oxidized and semiquinoid DAO, while zwitterionic ligands have high affinity for anionic forms of oxidized, semiquinoid, and reduced DAO; this difference was explained by the electrostatic interaction in the active site. The low affinity of homarine (N-methylpicolinate) for oxidized DAO, as in the case of o-methylbenzoate, is due to steric hindrance: one of the ortho carbons of benzoate is near the phenol carbons of Tyr228 and the other ortho carbon is near the carbonyl oxygen of Gly313. The correlation of the affinity of meta- and para-substituted benzoates for oxidized DAO with their Hammet's s values are explained by the HOMO-LUMO interaction between the phenol group of Tyr224 and the benzene ring of benzoate derivative. The pK(a) of neutral flavin [N(3)-H of oxidized flavin, N(5)-H of semiquinoid flavin, and N(1)-H of reduced flavin] decreases by its binding to the apoenzyme. The magnitude of the decrement is oxidized flavin < semiquinoid flavin < reduced flavin. The largest factor in the substantially low pK(a) of reduced flavin in DAO is probably the steric hindrance between the hydrogen atom of H-N(1)(flavin) and the hydrogen atom of H-N of Gly315, which becomes significant when a hydrogen is bound to N(1) of flavin.

Substrate recognition and activation mechanism of D-amino acid oxidase: a study using substrate analogs. Publishing Authors By Initials

Y Nishina,K Sato,R Miura,K Shiga,

For similar natural sciences: physics: thermodynamics research abstracts see: natural sciences: physics: thermodynamics research

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Substrate recognition and activation mechanism of D-amino acid oxidase: a study using substrate analogs. Journal Published:

PUBLICATION TYPE: Journal Article

Journal: Journal of biochemistry

VOLUME: 128

Page Numbers: 213-23

Journal Abbreviation: J. Biochem.

ISSN: 0021-924X

DAY: 19

MONTH: Aug

YEAR: 2000

Substrate recognition and activation mechanism of D-amino acid oxidase: a study using substrate analogs. Information

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LANGUAGE: eng

NlmUniqueID: 376600

Substrate recognition and activation mechanism of D-amino acid oxidase: a study using substrate analogs. Keywords Mesh Terms:

KEYWORDS: Thermodynamics

MESH TERMS: chemistry

Chemical & Substance for Abstract: Substrate recognition and activation mechanism of D-amino acid oxidase: a study using substrate analogs. Information

Substance Name: D-Amino-Acid Oxidase

Registry Number: EC 1.4.3.3

Grant and Affiliation Information for Substrate recognition and activation mechanism of D-amino acid oxidase: a study using substrate analogs.

AFFILIATION: Departments of Physiology and Biochemistry, Kumamoto University School of Medicine, Honjo, Kumamoto 860-0811, Japan. nishina@kaiju. medic.kumamoto-u.ac.jp

Country: JAPAN

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MEDLINETA: J Biochem

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