• 한국미생물·생명공학회지
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• 제34권4호
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• pp.368-372
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• 2006

Quercetin은 flavonoid 계통의 물질로서 자연계에서 채소나 과일에 매우 흔하다. 또한 인체에서는 radical scavenger로서 신체항상성 뿐만 아니라 직장암의 예방에도 중요한 역할을 한다. Glucosidase를 포함한 glycosidase는 많은 종류의 대사성 질환에 관련이 있다. 유용한 $\alpha$-glucosidase 저해제를 스크리닝 하던 중 chemical library로부터 quercetin을 선별하였다. Quercetin은 $\alpha$-glucosidase에 가역적으로, 느리게 결합하며, 비경쟁적인 저해제인데, $6.3\times10^{-8}$ M의 Ki값을 가진다. 이러한 결과는 비록 기전 연구가 더 필요하지만, quercetin이 당뇨병과 같은 퇴행성 질환을 치료할 수 있다는 잠재성을 보여주는 것이다.

• BMB Reports
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• 제31권1호
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• pp.25-30
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• 1998

Kinetic studies of L-Alanine dehydrogenase from Bacillus subtilis-catalyzed reactions in the presence of $Zn^{2+}$ were carried out. The substrate (L-alanine) saturation curve is hyperbolic in the absence of the metal ion but it becomes sigmoidal when $Zn^{2+}$ is added to the reaction mixture indicating the positive cooperative binding of the substrate in the presence of zinc ion. The cooperativity of substrate binding depends on the xinc ion concentration: the Hill coefficients ($n_H$) varied from 1.0 to 1.95 when the zinc ion concentration varied from 0 to $60\;{\mu}m$. The inhibition of AlaDH by $Zn^{2+}$ is reversible and noncompetitive with respect to $NAD^+$ ($K_i\;=\;5.28{\times}10^{-5}\;M$). $Zn^{2+}$ itself binds to AlaDH with positive cooperativity and the cooperativity is independent of substrate concentration. The Hill coefficients of substrate biding in the presence of $Zn^{2+}$ are not affected by the enzyme concentration indicating that $Zn^{2+}$ binding does not change the polymerization-depolymerization equilibria of the enzyme. Among other metal ions, $Zn^{2+}$ appears to be a specific reversible inhibitor inducing conformational change through the intersubunit interaction. These results indicate that $Zn^{2+}$ is an allosteric competitive inhibitor and substrate being a non-cooperative per se, excludes the $Zn^{2+}$ from its binding site and thus exhibits positive cooperativity. The allosteric mechanism of AlaDh from Bacillus subtilis is consistent with both MWC and Koshland's allosteric model.

• Journal of Applied Biological Chemistry
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• 제61권2호
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• pp.187-190
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• 2018

Two curcumin derivatives, demethoxycurcumin (DMC) and bisdemethoxycurcumin (BDMC), isolated from Curcuma longa were analyzed for their inhibitory activities against two isoforms of monoamine oxidase (MAO), which is involved in the catalysis of neurotransmitting monoamines. In the study, DMC and BDMC potently inhibited human MAO-B, with $IC_{50}$ values of 2.45 and $2.59{\mu}M$, respectively, and both compounds showed effective inhibitory activities against human MAO-A, with $IC_{50}$ values of 3.24 and $3.09{\mu}M$, respectively. The inhibitory activities of the two compounds were higher than those of curcumin. The removal of the methoxy or dimethoxy groups in curcumin might increase the inhibitory activities against human MAO-A and MAO-B. The inhibited activities were recovered to almost the values of the reversible references in the dialysis experiments with DMC and BDMC. DMC and BDMC showed competitive inhibition for MAO-A and MAO-B, respectively, with $K_i$ values of 0.91 and $0.80{\mu}M$, respectively. These results suggest that the two curcumin derivatives may be useful or lead compounds in the treatment of related disorders as potent reversible MAO inhibitors.

• 대한화학회지
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• 제20권5호
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• pp.406-416
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• 1976

Pyridine관여 탈수소 효소는 $N^1$-alkylnicotinamide chloride 유도체에 의하여 저해 작용을 받고 있는 바 저해제이 농도 변화에 따른 효소 저해작용이 가역 또는 비가역 불활성화 반응에 기인하는지의 여부를 밝혀 보기 위하여 토끼 근육으로 부터 유리한 L-${\alpha}$-glycerophosphate dehydrogenase를 사용하여 연구하였다. 이 효소의 저해작용은 상용한 저해제 유도체의 농도가 희박했을 경우 가역적인 효소저해 반응을 보여주고 있으나 저해제의 농도가 증가함에 따라 점차 비가역적인 효소 불활성화로서 나타남을 알았으며 이러한 비가역 불활성화 반응은 저해제의 농도가 증가함에 따라 형성될 수 있는 micelle 구조의 미세분자와의 결합에 의한 효소의 변성에 기인할 것이라고 결론을 얻었다.

• Bulletin of the Korean Chemical Society
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• 제3권3호
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• pp.122-129
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• 1982

In order to extend our understanding on the multiple inhibition enzyme kinetics, a general equation of an enzyme reaction in the presence of two different reversible inhibitors was derived by what we call "match-box mechanism" under the combined assumption of steady-state and quasi-equilibrium for inhibitor binding. Graphical methods were proposed to analyze the multiple inhibition of an enzyme by any given sets of different inhibitors, i.e., competitive, noncompetitive, and uncompetitive inhibitors. This method not only gives an interaction factor $({\alpha})$ between two inhibitors, but also discerns ${\alpha}_1$ and ${\alpha}_2$ with and without substrate binding, respectively. The factors involved in the dissociation constants of inhibitors can also be evaluated by the present plot. It is also shown that the present kinetic approach can be extended to other forms of activators or hydrogen ions with some modification.

• Archives of Pharmacal Research
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• 제25권6호
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• pp.817-819
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• 2002

In the course of screening Korean natural products for acetylcholinesterase (AChE) inhibitory activity, it was found that a methanolic extract of the aerial parts of Corydalis incisa (Papaveraceae) showed significant inhibitory effects on AChE. Corynoline isolated from this plant inhibited AChE activity in a dose-dependent manner, and the $IC_{50}$ value of corynoline was $30.6{\;}{\mu}M$. The AChE inhibitory activity of corynoline was reversible and noncompetitive.

• Bulletin of the Korean Chemical Society
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• 제17권1호
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• pp.34-38
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• 1996

2-(Azetidin-2-one-1-yl)-3-phenylpropionic acid and 2-(azetidin-2-thione-1-yl)-3-phenylpropionic acid were designed as potential active site directed inactivators for carboxypeptidase A, but shown to be they are competitive reversible inhibitors for the enzyme. The observation was somewhat surprising, but is not unexpected considering the recent report of Page who questioned the validity of the generally believed notion that $\beta-lactam$ ring is highly unstable.

• 대한약학회:학술대회논문집
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• 대한약학회 2001년도 Proceedings of the Pharmaceutical Society of Korea
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• pp.238.1-238.1
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• 2001

• Journal of Microbiology and Biotechnology
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• 제10권5호
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• pp.606-611
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• 2000

Dimorphic yeast Candida albicans reversibly switches between the form of yeast and hyphae depending on external conditions. We investigated possible roles of the myosin family in the growth and dimorphic switches of C. albicans with a general myosin ATPase inhibitor, 2,3-butanedione-2-monoxime (BDM). Transition to hyphae as well as proliferation by budding was completely inhibited by BDM at 16 mM. Presence of 16 mM BDM did not affect hyphae-to-bud transition but it blocked budding. The effects of BDM on yeast growth and dimorphic switches were reversible. More than 70% of the BDM-treated cells demonstrated defects in the amount and the polarized localization of F-actin as well as in the shape and migration of the nucleus, suggesting that myosin activities are needed in these cellular processes of C. albicans.

• The Korean Journal of Physiology and Pharmacology
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• 제12권5호
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• pp.259-265
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• 2008

$[Ca^{2+}]_i$ transients by reverse mode of cardiac $Na^+/Ca^{2+}$ exchanger (NCX1) were recorded in fura-2 loaded BHK cells with stable expression of NCX1. Repeated stimulation of reverse NCX1 produced a long-lasting decrease of $Ca^{2+}$ transients ('rundown'). Rundown of NCX1 was independent of membrane $PIP_2$ depletion. Although the activation of protein kinase C (PKC) was observed during the $Ca^{2+}$ transients, neither a selective PKC inhibitor (calphostin C) nor a PKC activator (PMA) changed the degrees of rundown. By comparison, a non-specific PKC inhibitor, staurosporine (STS), reversed rundown in a dose-dependent and reversible manner. The action of STS was unaffected by pretreatment of the cells with calphostin C, PMA, or forskolin. Taken together, the results suggest that the stimulation of reverse NCX1 by STS is independent of PKC and/or PKA inhibition.