Exploiting nucleotide thiophosphates to probe mechanistic aspects of Escherichia coli DNA gyrase

Biochemistry
P M CullisD P Weiner

Abstract

The interaction of DNA gyrase with ATP has been probed using a range of thiophosphate ATP analogs. ATP gammaS is not detectably hydrolyzed by gyrase but can support limited, probably catalytic, DNA supercoiling. ATP gammaS is a good inhibitor of both ATP hydrolysis and ATP-supported supercoiling. In contrast, both ATP alphaS(Rp) and ATP betaS(Rp) have been shown to be good substrates for the ATPase reaction of gyrase and to support catalytic DNA supercoiling. The corresponding Sp diastereoisomers do not support significant levels of supercoiling and are not readily hydrolyzed, but are shown to be reasonable inhibitors of gyrase. For ATP alphaS(Rp), the supercoiling and ATPase activities appear to be tightly coupled with the thionucleotide being apparently a better substrate than ATP in terms of both DNA supercoiling and nucleotide hydrolysis. In the case of ATP betaS(Rp), DNA supercoiling and nucleotide hydrolysis appear to be uncoupled in that ATP betaS(Rp) is almost as good a substrate as ATP for the ATPase reaction of both intact gyrase and the 43 kDa GyrB fragment, whereas it only supports slow DNA supercoiling; the mechanistic consequences of these observations are discussed in terms of a new model for energy coupling in g...Continue Reading

References

Nov 15, 1979·Analytical Biochemistry·P A LanzettaO A Candia
Oct 1, 1992·The Journal of Antimicrobial Chemotherapy·A Maxwell
Jan 1, 1991·Critical Reviews in Biochemistry and Molecular Biology·R J Reece, A Maxwell
Jan 1, 1990·Pharmacology & Therapeutics·S Rádl
Jan 1, 1985·Annual Review of Biochemistry·F Eckstein

❮ Previous
Next ❯

Citations

Mar 31, 1998·Current Opinion in Structural Biology·J M Berger
Jul 21, 1999·Proceedings of the National Academy of Sciences of the United States of America·S C KampranisA Maxwell
Sep 18, 1997·Microbiology and Molecular Biology Reviews : MMBR·K Drlica, X Zhao

❮ Previous
Next ❯

Related Concepts

Trending Feeds

COVID-19

Coronaviruses encompass a large family of viruses that cause the common cold as well as more serious diseases, such as the ongoing outbreak of coronavirus disease 2019 (COVID-19; formally known as 2019-nCoV). Coronaviruses can spread from animals to humans; symptoms include fever, cough, shortness of breath, and breathing difficulties; in more severe cases, infection can lead to death. This feed covers recent research on COVID-19.

Blastomycosis

Blastomycosis fungal infections spread through inhaling Blastomyces dermatitidis spores. Discover the latest research on blastomycosis fungal infections here.

Nuclear Pore Complex in ALS/FTD

Alterations in nucleocytoplasmic transport, controlled by the nuclear pore complex, may be involved in the pathomechanism underlying multiple neurodegenerative diseases including Amyotrophic Lateral Sclerosis and Frontotemporal Dementia. Here is the latest research on the nuclear pore complex in ALS and FTD.

Applications of Molecular Barcoding

The concept of molecular barcoding is that each original DNA or RNA molecule is attached to a unique sequence barcode. Sequence reads having different barcodes represent different original molecules, while sequence reads having the same barcode are results of PCR duplication from one original molecule. Discover the latest research on molecular barcoding here.

Chronic Fatigue Syndrome

Chronic fatigue syndrome is a disease characterized by unexplained disabling fatigue; the pathology of which is incompletely understood. Discover the latest research on chronic fatigue syndrome here.

Evolution of Pluripotency

Pluripotency refers to the ability of a cell to develop into three primary germ cell layers of the embryo. This feed focuses on the mechanisms that underlie the evolution of pluripotency. Here is the latest research.

Position Effect Variegation

Position Effect Variagation occurs when a gene is inactivated due to its positioning near heterochromatic regions within a chromosome. Discover the latest research on Position Effect Variagation here.

STING Receptor Agonists

Stimulator of IFN genes (STING) are a group of transmembrane proteins that are involved in the induction of type I interferon that is important in the innate immune response. The stimulation of STING has been an active area of research in the treatment of cancer and infectious diseases. Here is the latest research on STING receptor agonists.

Microbicide

Microbicides are products that can be applied to vaginal or rectal mucosal surfaces with the goal of preventing, or at least significantly reducing, the transmission of sexually transmitted infections. Here is the latest research on microbicides.