The first crystal structure of a thioacylenzyme intermediate in the ALDH family: new coenzyme conformation and relevance to catalysis

Biochemistry
Katia D'AmbrosioCatherine Corbier

Abstract

Crystal structures of several members of the nonphosphorylating CoA-independent aldehyde dehydrogenase (ALDH) family have shown that the peculiar binding mode of the cofactor to the Rossmann fold results in a conformational flexibility for the nicotinamide moiety of the cofactor. This has been hypothesized to constitute an essential feature of the catalytic mechanism because the conformation of the cofactor required for the acylation step is not appropriate for the deacylation step. In the present study, the structure of a reaction intermediate of the E268A-glyceraldehyde 3-phosphate dehydrogenase (GAPN) from Streptococcus mutans, obtained by soaking the crystals of the enzyme/NADP complex with the natural substrate, is reported. The substrate is bound covalently in the four monomers and presents the geometric characteristics expected for a thioacylenzyme intermediate. Control experiments assessed that reduction of the coenzyme has occurred within the crystal. The structure reveals that reduction of the cofactor upon acylation leads to an extensive motion of the nicotinamide moiety with a flip of the reduced pyridinium ring away from the active site without significant changes of the protein structure. This event positions the ...Continue Reading

References

Feb 1, 1996·Journal of Molecular Graphics·R KoradiK Wüthrich

❮ Previous
Next ❯

Citations

Jan 12, 2010·Nature Structural & Molecular Biology·Samantha Perez-MillerThomas D Hurley
May 5, 2011·The Journal of Biological Chemistry·Yaroslav Tsybovsky, Sergey A Krupenko
Sep 17, 2013·Biochemistry and Cell Biology = Biochimie Et Biologie Cellulaire·Denis ArutyunovVladimir Muronetz
Aug 19, 2007·Journal of Molecular Microbiology and Biotechnology·Paul SchweigerUwe Deppenmeier
Oct 12, 2007·Bioscience, Biotechnology, and Biochemistry·Ittipon SaichanaHirohide Toyama
Apr 26, 2011·The Journal of Biological Chemistry·François TalfournierGuy Branlant
Feb 15, 2013·The Journal of Biological Chemistry·David KopečnySolange Moréra
Jul 10, 2008·Expert Opinion on Drug Metabolism & Toxicology·Satori A MarchittiVasilis Vasiliou
Mar 19, 2013·Journal of Structural Biology·Zuanning YuanYu-ren Adam Yuan
Dec 12, 2012·Chemico-biological Interactions·Héctor Riveros-RosasRosario A Muñoz-Clares
Jan 9, 2013·Chemico-biological Interactions·Lilian González-SeguraThomas D Hurley
Oct 27, 2012·Progress in Retinal and Eye Research·Ying ChenVasilis Vasiliou
Nov 26, 2008·Chemico-biological Interactions·François TalfournierGuy Branlant
Apr 16, 2011·Protein Science : a Publication of the Protein Society·Jasleen BainsMartin J Boulanger
Jan 27, 2015·Chemico-biological Interactions·Rosario A Muñoz-ClaresAdriana Julián-Sánchez
Feb 22, 2017·Journal of Medicinal Chemistry·Cameron D Buchman, Thomas D Hurley
Dec 14, 2016·Archaea : an International Microbiological Journal·Ekaterina Yu BezsudnovaVladimir O Popov
Aug 29, 2020·Nature Communications·Saken SherkhanovJames U Bowie
Jun 1, 2021·Frontiers in Molecular Biosciences·Kim ShortallTewfik Soulimane
Feb 7, 2012·Organic Letters·Simon P Curran, Stephen J Connon
Sep 22, 2009·Archives of Biochemistry and Biophysics·Rosario A Muñoz-ClaresCarmina Montiel

❮ 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.