Mechanism of Inhibition of Glucose and Proton Cotransport Protein GlcPSe by Cytochalasin B

Chem. J. Chinese Universities ›› 2022, Vol. 43 ›› Issue (4): 20210822.doi: 10.7503/cjcu20210822

• Physical Chemistry • Previous Articles Next Articles

Mechanism of Inhibition of Glucose and Proton Cotransport Protein GlcPSe by Cytochalasin B

ZENG Xianyang, ZHAO Xi(), HUANG Xuri()

Institute of Theoretical Chemistry，Jilin University，Changchun 130061，China

Received:2021-12-07 Online:2022-04-10 Published:2022-01-26
Contact: ZHAO Xi,HUANG Xuri E-mail:zhaoxi@jlu.edu.cn;huangxr@jlu.edu.cn
Supported by:
the Program of Jilin Provincial Department of Education, China(jjkh20180334)

Abstract

Abstract:

Two protonated states of glucose/H⁺ symporter with cytochalasin B were simulated by means of molecular dynamics experiments. It was concluded that cytochalasin B has a better inhibitory effect on glucose transporter proteins in the deprotonation phase. It was found that tryptophan 357 and proline 117 are key amino acids for glucose transporter protein binding to cytochalasin B. Not only that， but when the inhibitor acts， the relative position of tryptophan 357 located on the TM10 to cytochalasin B is important for the binding of the inhibitor. These new findings provide a molecular basis for the understanding of the mechanism of glucose-proton cotransport protein inhibition and the development of drug targets for it.

Key words: Glucose/H⁺ symporter protein, Staphylococcus epidermidis, Cytochalasin B, Molecular dynamics

CLC Number:

O641

TrendMD:

ZENG Xianyang, ZHAO Xi, HUANG Xuri. Mechanism of Inhibition of Glucose and Proton Cotransport Protein GlcPSe by Cytochalasin B[J]. Chem. J. Chinese Universities, 2022, 43(4): 20210822.

Figures/Tables 13

Table 1 Summary of binding free energy

U v d W f / (k J · m o l - 1)

U v d W b / (k J · m o l - 1)

U e l f / (k J · m o l - 1)

U e l b / (k J · m o l - 1)

Δ G L I E / (k J · m o l - 1)

Δ G E X P / (k J · m o l - 1)

-28.144

-28.144

Table 1 Summary of binding free energy

State

U v d W f / (k J · m o l - 1)

U v d W b / (k J · m o l - 1)

U e l f / (k J · m o l - 1)

U e l b / (k J · m o l - 1)

Δ G L I E / (k J · m o l - 1)

Δ G E X P / (k J · m o l - 1)

No protonized

-163.251±0.84

-272.733±0.4

-101.391±1.2

-116.728±4.2

-24.876

-28.144

-28.144

Protonized

-181.786±0.84

-262.093±1.3

-65.427±1.2

-113.781±2

-20.737

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