QM/MM computations reveal details of the acetyl-CoA synthase catalytic center

Biochimica Et Biophysica Acta. General Subjects
Nadia Elghobashi-MeinhardtMaria-Andrea Mroginski

Abstract

The "open" (Aopen) and "closed" (Aclosed) A-clusters of the acteyl-CoA synthase (ACS) enzyme from Moorella thermoacetica have been studied using a combined quantum mechanical (QM)/molecular mechanical (MM) approach. Geometry optimizations of the oxidized, one- and two-electron reduced Aopen state have been carried out for the fully solvated ACS enzyme, and the CO ligand has been modeled in the reduced models. Using a combination of both αopen and αclosed protein scaffolds and the positions of metal atoms in these structures, we have been able to piece together critical parts of the catalytic cycle of ACS. We have replaced the unidentified exogenous ligand in the crystal structure with CO using both a square planar and tetrahedral proximal Ni atom. A one-electron reduced A-cluster that is characterized by a proximal Ni atom in a tetrahedral coordination pattern observed in both the Aopen (lower occupancy proximal Ni) and Aclosed (proximal Zn atom) geometries with three cysteine thiolates and a modeled CO ligand demonstrates excellent agreement with the crystal structure atomic positions, particularly with the displacement of the side chain ring of Phe512 which appears to serve as a structural gate for ligand binding. The QM/MM o...Continue Reading

References

Feb 1, 1991·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·H G Wood
Jan 1, 1986·Annual Review of Microbiology·L G Ljungdahl
Aug 23, 2001·Proceedings of the National Academy of Sciences of the United States of America·N A BakerJ A McCammon
Oct 19, 2002·Science·Tzanko I DoukovCatherine L Drennan
Aug 2, 2003·Journal of the American Chemical Society·Matthew R BramlettPaul A Lindahl
Dec 31, 2003·Proceedings of the National Academy of Sciences of the United States of America·Vitali SvetlitchnyiOrtwin Meyer
Mar 18, 2004·Journal of the American Chemical Society·Charles Edwin WebsterMichael B Hall
Mar 31, 2004·Biochemistry·Javier SeravalliStephen W Ragsdale
Jun 29, 2004·Journal of Biological Inorganic Chemistry : JBIC : a Publication of the Society of Biological Inorganic Chemistry·Anne Volbeda, Juan C Fontecilla-Camps
Feb 24, 2005·Journal of the American Chemical Society·Patricia AmaraMartin J Field
Dec 7, 2007·Proteins·Gernot Kieseritzky, Ernst-Walter Knapp
May 30, 2013·Journal of the American Chemical Society·Po-hung WangJochen Blumberger
Oct 4, 2013·The Journal of Physical Chemistry. a·Aleksandra ChmielowskaMaria Jaworska
Apr 30, 1998·The Journal of Physical Chemistry. B·A D MacKerellM Karplus
Nov 18, 2015·Journal of Chemical Theory and Computation·Tim Meyer, Ernst-Walter Knapp
Apr 2, 2019·The Journal of Physical Chemistry. B·Daria Tombolelli, Maria Andrea Mroginski

❮ Previous
Next ❯

Citations

Mar 5, 2021·Biochimica Et Biophysica Acta. General Subjects·Jerome BaudryBenoit Roux
Oct 6, 2020·Inorganic Chemistry·Shi-Lu Chen, Per E M Siegbahn

❮ 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.

Related Papers

Journal of the American Chemical Society
Matthew R BramlettPaul A Lindahl
Environmental Science & Technology
The Journal of Physical Chemistry Letters
Darla P Henderson
Giornale italiano di cardiologia : organo ufficiale della Federazione italiana di cardiologia : organo ufficiale della Società italiana di chirurgia cardiaca
Michele GalliGianluca Campo
© 2021 Meta ULC. All rights reserved