The rate-limiting catalytic steps of hydroxymandelate synthase from Amycolatopsis orientalis

Biochemistry
Panqing HeGraham R Moran

Abstract

Hydroxymandelate synthase (HMS) catalyzes the committed step in the formation of p-hydroxyphenylglycine, a recurrent substructure of polycyclic nonribosomal peptide antibiotics such as vancomycin. HMS has the same structural fold as and uses the same substrates as 4-hydroxyphenylpyruvate dioxygenase (HPPD) (4-hydroxyphenylpyruvate (HPP) and O(2)). Moreover, HMS catalyzes a very similar dioxygenation reaction to that of HPPD, adding the second oxygen atom to the benzylic position, rather than the aromatic C1 carbon of the substrate. The dissociation constant for HPP (59 microM) was measured under anaerobic conditions by titrating substrate with enzyme and monitoring the intensity of the weak (epsilon(475nm ) approximately 250 M(-1) cm(-1)) charge-transfer absorption band of the HMS.Fe(II).HPP complex. Pre-steady-state analysis indicates that evidence exists for the accumulation of three intermediates in a single turnover and the decay of the third is rate-limiting in multiple turnovers. The rate constants used to fit the data were k(1) = 1 x 10(5) M(-1) s(-1), k(2) = 250 s(-1), k(3) = 5 s(-1), and k(4) = 0.3 s(-1). However, the values for k(1) and k(2) could not be accurately measured due to both a prolonged mixing time for the ...Continue Reading

References

Nov 1, 1995·Protein Science : a Publication of the Protein Society·C N PaceT Gray
Jul 18, 2001·Journal of the American Chemical Society·R Y HoL Que
Oct 31, 2001·European Journal of Biochemistry·C M HarrisS Ghisla
Apr 16, 2004·Plant Physiology·Iris M FritzeStefan Steinbacher
May 4, 2004·Critical Reviews in Biochemistry and Molecular Biology·Robert P Hausinger
Dec 8, 2004·Archives of Biochemistry and Biophysics·Graham R Moran
Sep 24, 2005·Current Pharmaceutical Design·Lihua Li, Bing Xu
Aug 22, 2006·Proceedings of the National Academy of Sciences of the United States of America·Michael L NeidigEdward I Solomon
Sep 28, 2006·Proceedings of the National Academy of Sciences of the United States of America·Lee M HoffartCarsten Krebs
Jan 16, 2007·Nature Chemical Biology·Danica P GalonićCarsten Krebs
Apr 14, 2007·Journal of Biological Inorganic Chemistry : JBIC : a Publication of the Society of Biological Inorganic Chemistry·Vincent Purpero, Graham R Moran

❮ Previous
Next ❯

Citations

Feb 6, 2020·Chemistry, an Asian Journal·Lijun LiuJifeng Yuan
Aug 27, 2014·Journal of the American Chemical Society·Anna WójcikTomasz Borowski
Sep 15, 2017·Journal of Agricultural and Food Chemistry·Ferdinand NdikuryayoGuang-Fu Yang

❮ 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.