Investigating Substrate Analogues for Mycobacterial MenJ: Truncated and Partially Saturated Menaquinones

Biochemistry
Jordan T KoehnDebbie C Crans

Abstract

Menaquinones (MKs) are essential for electron transport in prokaryotes, and importantly, partially saturated MKs represent a novel virulence factor. However, little is known regarding how the degree of saturation in the isoprenyl side chain influences conformation or quinone redox potential. MenJ is an enzyme that selectively reduces the second isoprene unit on MK-9 and is contextually essential for the survival of Mycobacterium tuberculosis in J774A.1 macrophage-like cells, suggesting that MenJ may be a conditional drug target for pathogenic mycobacteria. Therefore, fundamental information about the properties of this system is important, and we synthesized the simplest MKs, unsaturated MK-1 and the saturated analogue, MK-1(H2). Using two-dimensional nuclear magnetic resonance spectroscopy, we established that MK-1 and MK-1(H2) adopted similar folded-extended conformations (i.e., the isoprenyl side chain folds upward) in each solvent examined but the folded-extended conformations differed slightly between organic solvents. Saturation of the isoprenyl side chain slightly altered the MK-1 analogue conformation in each solvent. We used molecular mechanics to illustrate the MK-1 analogue conformations. The measured quinone redox p...Continue Reading

References

Jan 1, 1992·Toxicology and Applied Pharmacology·T J MonksD G Graham
Dec 7, 2000·Biophysical Journal·E J VeldhuizenH P Haagsman
Oct 23, 2004·Bioorganic & Medicinal Chemistry·Richard J PayneAndrew D Abell
Aug 27, 2005·Advances in Colloid and Interface Science·R WüstneckU Pison
Oct 1, 2005·Chemistry : a European Journal·Yuri Diaz-FernandezSimon Rodriguez-Calvo
Jun 2, 2006·Chemistry : a European Journal·Michael P Schramm, Julius Rebek
Jul 26, 2006·The Journal of Physical Chemistry. B·Jeffery B KlaudaRichard W Pastor
Sep 28, 2006·Journal of the American Chemical Society·Bharat BaruahNancy E Levinger
Apr 30, 2008·Angewandte Chemie·Young Ho KoKimoon Kim
May 20, 2008·Langmuir : the ACS Journal of Surfaces and Colloids·Michelle L StahlaDebbie C Crans
Mar 26, 2010·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Michio Kurosu, Eeshwaraiah Begari
Jul 6, 2010·Biochimica Et Biophysica Acta·Beatrycze Nowicka, Jerzy Kruk
Sep 17, 2010·Physical Chemistry Chemical Physics : PCCP·Paula ToimilFélix Sarmiento
Dec 30, 2010·Langmuir : the ACS Journal of Surfaces and Colloids·Myles A SedgwickDebbie C Crans
Jan 22, 2011·Chemistry, an Asian Journal·Young Ho KoKimoon Kim
Mar 31, 2011·Beilstein Journal of Organic Chemistry·Catharine R JonesJeremy N Harvey
May 15, 2012·Science·Melissa VosPatrik Verstreken
Jul 26, 2012·Magnetic Resonance in Chemistry : MRC·Tuulia TynkkynenReino Laatikainen
Jul 28, 2012·Journal of Colloid and Interface Science·Javier HoyoEster Guaus
Jan 19, 2013·Journal of Medicinal Chemistry·Benjamin J JoseyC James Chou
Mar 13, 2014·Advances in Colloid and Interface Science·Cristina StefaniuHelmuth Möhwald
Jun 24, 2014·Langmuir : the ACS Journal of Surfaces and Colloids·Nuttaporn SamartDebbie C Crans
Jul 11, 2014·Current Organic Chemistry·Sarah K Jarchow-ChoyDavid T Fox
Nov 2, 2014·Cold Spring Harbor Perspectives in Medicine·Philippe GlaziouMario Raviglione
Mar 17, 2015·Biochimica Et Biophysica Acta·Javier HoyoFausto Sanz
Apr 12, 2015·FEMS Microbiology Reviews·Christian Sohlenkamp, Otto Geiger
Jan 6, 2016·Advanced Materials·Guangtao Zan, Qingsheng Wu
Feb 20, 2016·Chemphyschem : a European Journal of Chemical Physics and Physical Chemistry·Andres M DurantiniN Mariano Correa
Mar 24, 2016·Synthesis·Aaron M TeitelbaumAllan E Rettie
Apr 30, 2016·Chemphyschem : a European Journal of Chemical Physics and Physical Chemistry·Emmanuel OdellaN Mariano Correa
Aug 3, 2016·Langmuir : the ACS Journal of Surfaces and Colloids·Benjamin J PetersDebbie C Crans
Jul 1, 2018·Langmuir : the ACS Journal of Surfaces and Colloids·Benjamin J PetersDebbie C Crans
Aug 10, 2018·ACS Chemical Biology·Ashutosh UpadhyayDean C Crick

❮ Previous
Next ❯

Citations

Oct 3, 2020·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Margaret Braasch-Turi, Debbie C Crans

❮ 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.