Substrate specificity, substrate channeling, and allostery in BphJ: an acylating aldehyde dehydrogenase associated with the pyruvate aldolase BphI

Biochemistry
Perrin BakerStephen Y K Seah

Abstract

BphJ, a nonphosphorylating acylating aldehyde dehydrogenase, catalyzes the conversion of aldehydes to form acyl-coenzyme A in the presence of NAD(+) and coenzyme A (CoA). The enzyme is structurally related to the nonacylating aldehyde dehydrogenases, aspartate-β-semialdehyde dehydrogenase and phosphorylating glyceraldehyde-3-phosphate dehydrogenase. Cys-131 was identified as the catalytic thiol in BphJ, and pH profiles together with site-specific mutagenesis data demonstrated that the catalytic thiol is not activated by an aspartate residue, as previously proposed. In contrast to the wild-type enzyme that had similar specificities for two- or three-carbon aldehydes, an I195A variant was observed to have a 20-fold higher catalytic efficiency for butyraldehyde and pentaldehyde compared to the catalytic efficiency of the wild type toward its natural substrate, acetaldehyde. BphJ forms a heterotetrameric complex with the class II aldolase BphI that channels aldehydes produced in the aldol cleavage reaction to the dehydrogenase via a molecular tunnel. Replacement of Ile-171 and Ile-195 with bulkier amino acid residues resulted in no more than a 35% reduction in acetaldehyde channeling efficiency, showing that these residues are not ...Continue Reading

References

Nov 1, 1977·The Biochemical Journal·A K MacGibbonP D Buckley
Aug 3, 1976·Differentiation; Research in Biological Diversity·I Olsen, G Harris
Sep 1, 1990·Applied and Environmental Microbiology·R T Yan, J S Chen
Nov 1, 1981·Archives of Biochemistry and Biophysics·R C Vallari, R Pietruszko
Dec 21, 2002·Protein Science : a Publication of the Protein Society·Julio BlancoRonald E Viola
May 24, 2003·Proceedings of the National Academy of Sciences of the United States of America·Babu A ManjasettyAlice Vrielink
Jul 2, 2003·Acta Crystallographica. Section D, Biological Crystallography·Stefano RicagnoYlva Lindqvist
Oct 16, 2003·Proceedings of the National Academy of Sciences of the United States of America·Julio BlancoRonald E Viola
Jul 24, 2004·Acta Crystallographica. Section D, Biological Crystallography·Julio BlancoRonald E Viola
Jul 24, 2004·Acta Crystallographica. Section D, Biological Crystallography·Hélène DubourgAndré Aubry
Sep 25, 2004·Acta Crystallographica. Section D, Biological Crystallography·Julio BlancoRonald E Viola
Dec 2, 2004·Acta Crystallographica. Section D, Biological Crystallography·Gerard J KleywegtT Alwyn Jones
Oct 18, 2005·Journal of Molecular Biology·Christopher R FaehnleRonald E Viola
Dec 8, 2005·The Biochemical Journal·Claire Stines-ChaumeilGuy Branlant
Feb 21, 2008·Acta Crystallographica. Section A, Foundations of Crystallography·Masami YoshizawaTakaaki Kawamura
Mar 8, 2008·Acta Crystallographica. Section D, Biological Crystallography·Ronald E ViolaChristopher R Faehnle
Nov 26, 2008·Chemico-biological Interactions·François TalfournierGuy Branlant
May 12, 2010·Nucleic Acids Research·Liisa Holm, Päivi Rosenström
Apr 26, 2011·The Journal of Biological Chemistry·François TalfournierGuy Branlant
Nov 16, 2011·Journal of the American Chemical Society·Perrin Baker, Stephen Y K Seah
Mar 6, 2012·Biophysical Journal·Natalie E SmithBen Corry

❮ Previous
Next ❯

Citations

Jun 1, 2013·Applied Biochemistry and Biotechnology·Guido Sello, Patrizia Di Gennaro

❮ 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.