Synergistic, random sequential binding of substrates in cobalamin-independent methionine synthase.

Biochemistry
Rebecca E TaurogR G Matthews

Abstract

Cobalamin-independent methionine synthase (MetE) catalyzes the transfer of the N5-methyl group of methyltetrahydrofolate (CH(3)-H(4)folate) to the sulfur of homocysteine (Hcy) to form methionine and tetrahydrofolate (H(4)folate) as products. This reaction is thought to involve a direct methyl transfer from one substrate to the other, requiring the two substrates to interact in a ternary complex. The crystal structure of a MetE.CH(3)-H(4)folate binary complex shows that the methyl group is pointing away from the Hcy binding site and is quite distant from the position where the sulfur of Hcy would be, raising the possibility that this binary complex is nonproductive. The CH(3)-H(4)folate must either rearrange or dissociate before methyl transfer can occur. Therefore, determining the order of substrate binding is of interest. We have used kinetic and equilibrium measurements in addition to isotope trapping experiments to elucidate the kinetic pathway of substrate binding in MetE. These studies demonstrate that both substrate binary complexes are chemically and kinetically competent for methyl transfer and suggest that the conformation observed in the crystal structure is indeed on-pathway. Additionally, the substrates are shown to...Continue Reading

References

Jun 1, 1990·Proceedings of the National Academy of Sciences of the United States of America·H Jakubowski
May 1, 1972·Archives of Biochemistry and Biophysics·H F KungH Weissbach
Dec 30, 1968·Biochemical and Biophysical Research Communications·C D Whitfield, H Weissbach
Oct 1, 1981·Analytical Biochemistry·R A Furness, P C Loewen
Oct 21, 1999·Methods : a Companion to Methods in Enzymology·M M PierceB T Nall
Jun 1, 2000·The Journal of Biological Chemistry·H Jakubowski
Dec 2, 2000·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·E P QuinlivanJ Scott
Sep 18, 2002·Analytical Biochemistry·Hieronim Jakubowski
Apr 19, 2006·Biochemistry·Rebecca E Taurog, Rowena G Matthews

❮ Previous
Next ❯

Citations

Apr 19, 2006·Biochemistry·Rebecca E Taurog, Rowena G Matthews
Dec 30, 2014·Journal of Molecular Biology·Devinder K Ubhi, Jon D Robertus
Jun 22, 2011·Archives of Biochemistry and Biophysics·Devinder UbhiJon D Robertus
Jan 18, 2008·Journal of Molecular Recognition : JMR·Oksana Okhrimenko, Ilian Jelesarov
Apr 2, 2008·Annals of the New York Academy of Sciences·Stephen W Ragsdale
Sep 1, 2008·EcoSal Plus·Jorge C Escalante-Semerena, Martin J Warren

❮ 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.