Inhibitors of transketolase from Mycobacterium tuberculosis targeted towards both the diphosphate binding site and an adjacent hydrophobic subsite

Nilov, D. K.; Gushchina, I. V.; Shcherbakova, T. A.; Baldin, S. M.; Svedas, V. K.

doi:10.7868/S3034529425020089

PII

S30345294S0320972525020089-1

DOI

10.7868/S3034529425020089

Publication type

Article

Status

Published

Authors

D. K. Nilov

Occupation: Belozersky Institute of Physico-Chemical Biology, Research Computing Center
Affiliation:
Lomonosov Moscow State University
Lomonosov Moscow State University

I. V. Gushchina

Occupation: Faculty of Bioengineering and Bioinformatics
Affiliation: Lomonosov Moscow State University

T. A. Shcherbakova

Occupation: Belozersky Institute of Physico-Chemical Biology
Affiliation: Lomonosov Moscow State University

S. M. Baldin

Occupation: Belozersky Institute of Physico-Chemical Biology, Research Computing Center
Affiliation:
Lomonosov Moscow State University
Lomonosov Moscow State University

V. K. Svedas

Occupation: Research Computing Center, Faculty of Bioengineering and Bioinformatics
Affiliation:
Lomonosov Moscow State University
Lomonosov Moscow State University

Volume/ Edition

Volume 90 / Issue number 2

Pages

288-293

Abstract

Transketolase from Mycobacterium tuberculosis (mbTK) is involved in the pentose phosphate pathway essential for bacterial survival and thus constitutes an attractive target for the antituberculosis therapy. We found a new class of active site-targeted furan sulfonate inhibitors of mbTK that are capable of binding to both the thiamine diphosphate cofactor subsite and adjacent hydrophobic subsite Ile211-Leu402-Phe464, thereby suppressing enzyme activity. The most potent compound identified by computer screening, STK106769, was found to inhibit mbTK with IC₅₀ of 7 µM and suppress the growth of M. tuberculosis H37Rv strain. The hydrophobic subsite Ile211-Leu402-Phe464 of mbTK is substituted by significantly more polar residues in homologous human TK, which is an important factor determining the selectivity of binding of TK inhibitors.

Keywords

сульфонаты сульфогруппа ингибитор транскетолаза микобактерии туберкулёз молекулярное моделирование докинг

Date of publication

18.03.2026

Year of publication

2026

Number of purchasers

Views

References

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GOST	Baldin S., Gushchina I., Nilov D., Shcherbakova T., Svedas V. Inhibitors of transketolase from Mycobacterium tuberculosis targeted towards both the diphosphate binding site and an adjacent hydrophobic subsite // Biochemistry. – 2025. – V. 90. – Issue number 2 C. 288-293 . URL: https://biochemras.ru/s30345294s0320972525020089-1/?version_id=124127. DOI: 10.7868/S3034529425020089
MLA	Baldin, S. M, Gushchina, I. V, Nilov, D. K, Shcherbakova, T. A, Svedas, V. K "Inhibitors of transketolase from Mycobacterium tuberculosis targeted towards both the diphosphate binding site and an adjacent hydrophobic subsite." Biochemistry. 90.2 (2025).:288-293. DOI: 10.7868/S3034529425020089
APA	Baldin S., Gushchina I., Nilov D., Shcherbakova T., Svedas V. (2025). Inhibitors of transketolase from Mycobacterium tuberculosis targeted towards both the diphosphate binding site and an adjacent hydrophobic subsite. Biochemistry. vol. 90, no. 2, pp.288-293 DOI: 10.7868/S3034529425020089

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