Investigating Conformational Dynamics of Lewis Y Oligosaccharides and Elucidating Blood Group Dependency of Cholera Using Molecular Dynamics

ACS Omega
Rajarshi RoyParimal Kar

Abstract

Cholera is caused by Vibrio cholerae and is an example of a blood-group-dependent disease. Recent studies suggest that the receptor-binding B subunit of the cholera toxin (CT) binds histo-blood group antigens at a secondary binding site. Herein, we studied the conformational dynamics of Lewis Y (LeY) oligosaccharides, H-tetrasaccharides and A-pentasaccharides, in aqueous solution by conducting accelerated molecular dynamics (aMD) simulations. The flexible nature of both oligosaccharides was displayed in aMD simulations. Furthermore, aMD simulations revealed that for both oligosaccharides in the free form, 4C1 and 1C4 puckers were sampled for all but GalNAc monosaccharides, while either the 4C1 (GlcNAc, Gal, GalNAc) or 1C4 (Fuc2, Fuc3) pucker was sampled in the CT-bound forms. In aMD, the complete transition from the 4C1 to 1C4 pucker was sampled for GlcNAc and Gal in both oligosaccharides. Further, we have observed a transition from the open to closed conformer in the case of A-pentasaccharide, while H-tetrasaccharide remains in the open conformation throughout the simulation. Both oligosaccharides adopted an open conformation in the CT binding site. Moreover, we have investigated the molecular basis of recognition of LeY oligo...Continue Reading

References

Sep 1, 1977·Annals of Human Biology·D Barua, A S Paguio
May 17, 1990·Nature·F YamamotoS Hakomori
Apr 1, 1989·The Journal of Infectious Diseases·J D ClemensA M Svennerholm
Jan 1, 1995·Transactions of the Royal Society of Tropical Medicine and Hygiene·C O TacketM M Levine
Dec 25, 2003·Journal of Biomolecular Structure & Dynamics·D Jeya Sundara Sharmila, K Veluraja
Jan 24, 2004·Lancet·David A SackA K Siddique
Jul 21, 2004·Journal of Computational Chemistry·Eric F PettersenThomas E Ferrin
Jul 23, 2004·The Journal of Chemical Physics·Donald HamelbergJ Andrew McCammon
Oct 4, 2005·Journal of Computational Chemistry·David A CaseRobert J Woods
Oct 22, 2005·Infection and Immunity·Jason B HarrisStephen B Calderwood
May 16, 2007·Journal of Computational Chemistry·Parimal KarSiegfried Höfinger
Jul 14, 2007·The Journal of Physical Chemistry. B·Parimal KarSiegfried Höfinger
Sep 13, 2007·Journal of Computational Chemistry·Karl N KirschnerRobert J Woods
Feb 19, 2008·Cellular and Molecular Life Sciences : CMLS·J Sánchez, J Holmgren
Apr 10, 2008·PLoS Neglected Tropical Diseases·Jason B HarrisStephen B Calderwood
Mar 24, 2010·Blood·David J Anstee
May 21, 2011·The Journal of Physical Chemistry. B·Parimal KarVolker Knecht
Feb 22, 2012·Journal of Computer-aided Molecular Design·Parimal Kar, Volker Knecht
May 5, 2012·The Journal of Physical Chemistry. B·Parimal Kar, Volker Knecht
May 12, 2012·The Journal of Physical Chemistry. B·Parimal Kar, Volker Knecht
May 15, 2012·Journal of Chemical Theory and Computation·Andreas W GötzRoss C Walker
Jul 12, 2014·Journal of Biomolecular Structure & Dynamics·J Jino Blessy, D Jeya Sundara Sharmila
Jul 26, 2014·Journal of Chemical Theory and Computation·Yinglong MiaoJ Andrew McCammon
Mar 12, 2015·Acta Crystallographica. Section D, Biological Crystallography·Josef HouserMichaela Wimmerova
Nov 18, 2015·Journal of Chemical Theory and Computation·James A MaierCarlos Simmerling
Jul 9, 2013·Journal of Chemical Theory and Computation·Daniel R Roe, Thomas E Cheatham
Sep 10, 2013·Journal of Chemical Theory and Computation·Romelia Salomon-FerrerRoss C Walker
Sep 13, 2011·Journal of Chemical Theory and Computation·Shahidul M IslamPierre-Nicholas Roy
Apr 16, 2016·PLoS Pathogens·Julie Elisabeth HeggelundUte Krengel
Jul 13, 2016·The American Journal of Tropical Medicine and Hygiene·Jason B Harris, Regina C LaRocque
Feb 1, 2012·Molecular Informatics·Nadine Homeyer, Holger Gohlke
Sep 1, 2012·Biophysics Reviews·Suyong ReYuji Sugita
Feb 8, 2018·ACS Infectious Diseases·Amberlyn M WandsJennifer J Kohler

❮ Previous
Next ❯

Citations

Mar 25, 2021·Expert Review of Hematology·Serena EkmanXuan T Bui
Jul 28, 2021·Chemometrics and Intelligent Laboratory Systems : an International Journal Sponsored by the Chemometrics Society·Vijay H MasandMagdi E A Zaki

❮ Previous
Next ❯

Methods Mentioned

BETA
X-ray

Software Mentioned

cMD
Chimera
AMBER
Pyreweighting
Visual Molecular Dynamics ( VMD )
Cpptraj
MM

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.