Infectious diseases have affected 13.7 million patients, placing a heavy burden on society. Furthermore, inappropriate and unrequited utilization of antibiotics has led to antimicrobial resistance worldwide. However, well-established targeted screening of environmental isolates or compound libraries has produced limited new drugs. The current situation, in which drug development is delayed, bacterial evolution is occurring, and drug resistance is emerging, requires the development of new targets and/or new strategies to combat infections. Some novel antibacterial strategies have been proposed, among which disruption of protein balance by inhibiting transcription and translation machinery is one of the proven effective antimicrobial strategies. Molecular chaperonins could mediate the correct folding of proteins, especially under conditions such as high temperature and pressure. The GroEL/ES system has been confirmed as one of the key molecular chaperones for bacterial viability. Recent data have revealed the antibacterial activities of GroEL/ES-targeted compounds, highlighting the potential role of GroEL/ES in the development of novel antibiotics. In this brief review, we discuss the function of the GroEL/ES system and summarize the inhibitors of the GroEL/ES system. The GroEL/ES system may represent a promising drug target for the exploration of novel antibiotics.
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http://dx.doi.org/10.1021/acsptsci.4c00397 | DOI Listing |
ACS Pharmacol Transl Sci
January 2025
State Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau, Macao 999078, China.
Infectious diseases have affected 13.7 million patients, placing a heavy burden on society. Furthermore, inappropriate and unrequited utilization of antibiotics has led to antimicrobial resistance worldwide.
View Article and Find Full Text PDFProtein Expr Purif
January 2025
Manchester Institute of Biotechnology, Department of Chemistry, University of Manchester, 131 Princess St, Manchester, M1 7DN, United Kingdom. Electronic address:
Since their discovery in Mycobacterium tuberculosis (Mtb), F-dependent enzymes have been identified as both important drug targets and potential industrial biocatalysts, including for bioremediation of otherwise recalcitrant substrates. Mtb-FGD1, utilizes glucose 6-phosphate (G6P) as an electron donor for the reduction of F. Current expression systems for Mtb-FGD1 use Mycobacterium smegmatis as host, because of the tendency for it to form inclusion bodies in E.
View Article and Find Full Text PDFBioTech (Basel)
December 2024
State Research Center of Virology and Biotechnology VECTOR, Rospotrebnadzor, 630559 Koltsovo, Russia.
Heterologous protein expression often faces significant challenges, particularly when the target protein has posttranslational modifications, is toxic, or is prone to misfolding. These issues can result in low expression levels, aggregation, or even cell death. Such problems are exemplified by the expression of phospholipase p37, a critical target for chemotherapeutic drugs against pathogenic human orthopoxviruses, including monkeypox and smallpox viruses.
View Article and Find Full Text PDFArch Biochem Biophys
December 2024
Department of Pharmacology, The University of Michigan Medical School, Ann Arbor, MI, 48109, USA. Electronic address:
In this communication we reported a bacterial system that over-expressed full-length wild-type (WT) human CYP3A4 in Escherichia coli (E. coli) at a level of 495 nmol/L culture. This level of expression was achieved by cloning the cDNA sequence of CYP3A4 WT to a pLW01-P450 vector and co-expressing it with chaperones GroEL/ES in bacterial C41(DE3) cells.
View Article and Find Full Text PDFProtein Sci
August 2024
Department of Chemical and Structural Biology, Weizmann Institute of Science, Rehovot, Israel.
The Escherichia coli GroEL/ES chaperonin system facilitates protein folding in an ATP-driven manner. There are <100 obligate clients of this system in E. coli although GroEL can interact and assist the folding of a multitude of proteins in vitro.
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