Mechanism of inhibition of arginine kinase by flavonoids consistent with thermodynamics of docking simulation

Wang, Hua-Rong; Zhu, Wenshuai; Wang, Xiaoyun

doi:10.1016/j.ijbiomac.2011.08.017

Cited by 27 publications

(11 citation statements)

References 37 publications

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“…Data presented implicate inhibitory interaction between gallotannin and rTbAK as well as the quenching of rTBAK's fluorescence intensity. Gallotannin reduced the activity of the rTbAK to less than 30%, which is consistent with previous reports on the inhibitory potential of phenolic-related compounds on AK activity [14, 15]. Further kinetic analysis suggests that inhibition by gallotannin may be noncompetitive.…”

Section: Discussionsupporting

confidence: 91%

“…The respective low K i values obtained at varied concentrations of either L-arginine or ATP underscore the strong affinity of gallotannin for rTBAK. Earlier studies have demonstrated the inhibitory potential of flavonoids on the activity of arginine kinase [14, 15]. In these studies, effect of flavonoids or rutin on the arginine kinase enzyme was found to correspond to noncompetitive inhibition.…”

Section: Discussionmentioning

confidence: 98%

“…Total concentration of protein is [ B o ]. The fluorescent intensity is proportional to the concentration of protein given as

\begin{matrix} \frac{[B]}{[B_{o}]} = \frac{F}{F_{o}} . \end{matrix}

From (3), it can further be deduced as [14]

\begin{matrix} \log (\frac{F_{o} - F}{F}) = \log K + n \log [Q] . \end{matrix}

The plots of log⁡ ( F o − F / F ) versus log⁡ [ Q ] were based on (4) for gallotannin-rTbAK system at different temperatures. In order to gain more insights into the interactions between gallotannin and the rTbAK, thermodynamic parameters were calculated from Van't Hoff plots.…”

Section: Methodsmentioning

confidence: 99%

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Interaction between Gallotannin and a Recombinant Form of Arginine Kinase of Trypanosoma brucei: Thermodynamic and Spectrofluorimetric Evaluation

Adeyemi

Sulaiman

Iniaghe

2014

Journal of Biophysics

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Current chemotherapies against trypanosomiasis are beset with diverse challenges, a situation which underscores the numerous research efforts aimed at finding newer and effective treatments. Arginine kinase of trypanosome has been validated as target for drug development against trypanosomiasis. The present study investigated the interaction between a recombinant form of the arginine kinase (rTbAK) of trypanosome and gallotannin. The interaction between gallotannin and recombinant arginine kinase of Trypanosoma brucei caused significant decrease of enzyme activity. Kinetic analysis revealed the interaction to be of noncompetitive inhibition. Further thermodynamic analysis showed that the interaction between gallotannin and the recombinant arginine kinase was nonspontaneous and involved hydrophobic forces. The K sv values and the FRET analysis suggest that static quenching of fluorescence intensity by gallotannin was static. Data revealed inhibitory interactions between gallotannin and rTbAK of trypanosome. Although the mechanism of inhibition is not clear yet, molecular docking studies are ongoing to clearly define the inhibitory interactions between the gallotannin and rTbAK. The knowledge of such binding properties would enrich development of selective inhibitors for the arginine kinase of Trypanosoma brucei.

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Section: Discussionsupporting

confidence: 91%

Section: Discussionmentioning

confidence: 98%

“…Total concentration of protein is [ B o ]. The fluorescent intensity is proportional to the concentration of protein given as

\begin{matrix} \frac{[B]}{[B_{o}]} = \frac{F}{F_{o}} . \end{matrix}

From (3), it can further be deduced as [14]

\begin{matrix} \log (\frac{F_{o} - F}{F}) = \log K + n \log [Q] . \end{matrix}

Section: Methodsmentioning

confidence: 99%

See 1 more Smart Citation

Interaction between Gallotannin and a Recombinant Form of Arginine Kinase of Trypanosoma brucei: Thermodynamic and Spectrofluorimetric Evaluation

Adeyemi

Sulaiman

Iniaghe

2014

Journal of Biophysics

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“…5F). To further confirm the function of MjAK, the inhibitor quercetin (QU), which can inhibit the kinase activity of arginine kinase (18), was employed to examine the effect of MjAK inhibition on WSSV replication in vivo. We found that QU, a type of flavonoid, had little effect on the survival of shrimp at a low concentration (Fig.…”

Section: Mjcdc42 Inhibits Wssv Replication In Vivomentioning

confidence: 99%

Interaction of the Small GTPase Cdc42 with Arginine Kinase Restricts White Spot Syndrome Virus in Shrimp

Jiang

Wei

et al. 2017

J Virol

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Many types of small GTPases are widely expressed in eukaryotes and have different functions. As a crucial member of the Rho GTPase family, Cdc42 serves a number of functions, such as regulating cell growth, migration, and cell movement. Several RNA viruses employ Cdc42-hijacking tactics in their target cell entry processes. However, the function of Cdc42 in shrimp antiviral immunity is not clear. In this study, we identified a Cdc42 protein in the kuruma shrimp (Marsupenaeus japonicus) and named it MjCdc42. MjCdc42 was upregulated in shrimp challenged by white spot syndrome virus (WSSV). The knockdown of MjCdc42 and injection of Cdc42 inhibitors increased the proliferation of WSSV. Further experiments determined that MjCdc42 interacted with an arginine kinase (MjAK). By analyzing the binding activity and enzyme activity of MjAK and its mutant, ΔMjAK, we found that MjAK could enhance the replication of WSSV in shrimp. MjAK interacted with the envelope protein VP26 of WSSV. An inhibitor of AK activity, quercetin, could impair the function of MjAK in WSSV replication. Further study demonstrated that the binding of MjCdc42 and MjAK depends on Cys 271 of MjAK and suppresses the WSSV replication-promoting effect of MjAK. By interacting with the active site of MjAK and suppressing its enzyme activity, MjCdc42 inhibits WSSV replication in shrimp. Our results demonstrate a new function of Cdc42 in the cellular defense against viral infection in addition to the regulation of actin and phagocytosis, which has been reported in previous studies. IMPORTANCEThe interaction of Cdc42 with arginine kinase plays a crucial role in the host defense against WSSV infection. This study identifies a new mechanism of Cdc42 in innate immunity and enriches the knowledge of the antiviral innate immunity of invertebrates.

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“…To determine the involvement of AK in larval settlement, two commercial AK inhibitors, rutin ( M r = 610.52; Sangon) (Wu et al., ) and quercetin ( M r = 302.24; Sangon) (Wang et al., ), were used for larval settlement bioassay. Rutin and quercetin were prepared as 0.2 and 0.5 M stock solution in DMSO, respectively.…”

Section: Methodsmentioning

confidence: 99%

Characterization of Arginine Kinase in the Barnacle Amphibalanus Amphitrite and Its Role in the Larval Settlement

et al. 2016

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Energy metabolism is a key process in larval settlement of barnacles, but the underlying molecular mechanisms remain ambiguous. Arginine kinase (AK) mainly participates in energy metabolism in invertebrates. So far, its roles in barnacles have not been studied. In the present study, we raised an antibody against AK from Amphibalanus amphitrite Darwin to characterize the roles of AK in the larval settlement process. Among the developmental stages, AK was highly expressed during the cypris stage. Along with the aging process in cyprids, the level of AK decreased. The immunostaining results showed that AK was localized to muscular tissues in cyprids, including antennules, antennular muscles, and thoracic limbs. The larval settlement rate decreased and larval movement was inhibited in response to treatments with high concentrations of AK inhibitors (rutin and quercetin). These results demonstrated that AK was involved in the larval settlement of A. amphitrite through mediating energy supply in muscle tissues. Moreover, further analysis indicated that both the p38 MAPK and NO/cGMP pathways positively mediated the expression of AK in cyprids.

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Mechanism of inhibition of arginine kinase by flavonoids consistent with thermodynamics of docking simulation

Cited by 27 publications

References 37 publications

Interaction between Gallotannin and a Recombinant Form of Arginine Kinase of Trypanosoma brucei: Thermodynamic and Spectrofluorimetric Evaluation

Interaction between Gallotannin and a Recombinant Form of Arginine Kinase of Trypanosoma brucei: Thermodynamic and Spectrofluorimetric Evaluation

Interaction of the Small GTPase Cdc42 with Arginine Kinase Restricts White Spot Syndrome Virus in Shrimp

Characterization of Arginine Kinase in the Barnacle Amphibalanus Amphitrite and Its Role in the Larval Settlement

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