Antibiotics MDL 62,879 and kirromycin bind to distinct and independent sites of elongation factor Tu (EF-Tu)

Biochemistry
P LandiniK Islam

Abstract

Antibiotic MDL 62,879 inhibits bacterial protein synthesis by acting on elongation factor Tu (EF-Tu). In this study we show that the inhibition of protein synthesis by MDL 62,879 in an Escherichia coli cell-free system was fully reversed by addition of stoichiometric amounts of EF-Tu but not by large excesses of EF-Ts, ribosomes, or aa-tRNA. MDL 62,879 bound tightly to EF-Tu and formed a stable 1:1 MDL 62,879:EF-Tu (M:EF-Tu) complex. We show that binding of MDL 62,879 to EF-Tu strongly affects the interaction of EF-Tu with aa-tRNA and causes rapid dissociation of preformed EF-Tu.aa-tRNA complex, suggesting that inhibition of aa-tRNA binding is due to a conformational change in EF-Tu rather than competition for the aa-tRNA binding site. Indication of a conformational change in EF-Tu induced by MDL 62,879 is further confirmed by proteolytic cleavage experiments: MDL 62,879 binding strongly protects EF-Tu against trypsin cleavage. The observed effects of MDL 62,879 appear to be different from those of the kirromycin class of antibiotics, which also inhibit protein synthesis by binding to EF-Tu, suggesting two distinct binding sites. Indeed, the M:EF-Tu complex was able to bind stoichiometric amounts of kirromycin to form a 1:1:1 M...Continue Reading

References

Jul 15, 1977·European Journal of Biochemistry·G R Jacobson, J P Rosenbusch
May 6, 1976·Nature·G R Jacobson, J P Rosenbusch
Jan 1, 1985·Annual Review of Microbiology·A Parmeggiani, G W Swart
Jul 6, 1973·Nature·A Travers

❮ Previous
Next ❯

Citations

Dec 5, 1998·Biochimica Et Biophysica Acta·I M Krab, A Parmeggiani
Oct 3, 2006·Bioorganic & Medicinal Chemistry·Masaru HashimotoHyouta Himeno
Dec 31, 1997·The Journal of Biological Chemistry·J C Morris, K Mensa-Wilmot
Jul 23, 2020·Cell Chemical Biology·Alexander A Vinogradov, Hiroaki Suga
Feb 11, 2005·Chemical Reviews·Mark C BagleyXin Xiong

❮ Previous
Next ❯

Related Concepts

Related Feeds

Aminoglycosides

Aminoglycoside is a medicinal and bacteriologic category of traditional Gram-negative antibacterial medications that inhibit protein synthesis and contain as a portion of the molecule an amino-modified glycoside. Discover the latest research on aminoglycoside here.

Aminoglycosides (ASM)

Aminoglycoside is a medicinal and bacteriologic category of traditional Gram-negative antibacterial medications that inhibit protein synthesis and contain as a portion of the molecule an amino-modified glycoside. Discover the latest research on aminoglycoside here.

Antifungals (ASM)

An antifungal, also known as an antimycotic medication, is a pharmaceutical fungicide or fungistatic used to treat and prevent mycosis such as athlete's foot, ringworm, candidiasis, cryptococcal meningitis, and others. Discover the latest research on antifungals here.

Antifungals

An antifungal, also known as an antimycotic medication, is a pharmaceutical fungicide or fungistatic used to treat and prevent mycosis such as athlete's foot, ringworm, candidiasis, cryptococcal meningitis, and others. Discover the latest research on antifungals here.