Trading off stability against activity in extremophilic aldolases

Scientific Reports
Markus DickJörg Pietruszka

Abstract

Understanding enzyme stability and activity in extremophilic organisms is of great biotechnological interest, but many questions are still unsolved. Using 2-deoxy-D-ribose-5-phosphate aldolase (DERA) as model enzyme, we have evaluated structural and functional characteristics of different orthologs from psychrophilic, mesophilic and hyperthermophilic organisms. We present the first crystal structures of psychrophilic DERAs, revealing a dimeric organization resembling their mesophilic but not their thermophilic counterparts. Conversion into monomeric proteins showed that the native dimer interface contributes to stability only in the hyperthermophilic enzymes. Nevertheless, introduction of a disulfide bridge in the interface of a psychrophilic DERA did confer increased thermostability, suggesting a strategy for rational design of more durable enzyme variants. Constraint network analysis revealed particularly sparse interactions between the substrate pocket and its surrounding α-helices in psychrophilic DERAs, which indicates that a more flexible active center underlies their high turnover numbers.

References

Sep 1, 1993·Applied and Environmental Microbiology·P VölklK O Stetter
Dec 1, 1993·Proteins·A AmadeiH J Berendsen
Nov 27, 1995·Physical Review Letters·D J Jacobs, M F Thorpe
Mar 10, 2001·Microbiology and Molecular Biology Reviews : MMBR·C Vieille, G J Zeikus
Apr 11, 2001·Human Mutation·Z Wang, J Moult
Jun 8, 2001·Proteins·D J JacobsM F Thorpe
Sep 12, 2001·Current Opinion in Biotechnology·B HöckerR Sterner
Jun 6, 2003·Cellular and Molecular Life Sciences : CMLS·G Feller
Mar 24, 2004·Nature Reviews. Microbiology·Georges Feller, Charles Gerday
Sep 25, 2004·Acta Crystallographica. Section D, Biological Crystallography·Neratur K LokanathNaoki Kunishima
Oct 27, 2004·Trends in Biochemical Sciences·Neelan J MarianayagamJacqueline M Matthews
Jul 27, 2005·Proceedings of the National Academy of Sciences of the United States of America·Barbara A MethéClaire M Fraser
Nov 1, 2005·Current Opinion in Microbiology·Ksenia Egorova, Garabed Antranikian
Jan 13, 2006·International Journal of Systematic and Evolutionary Microbiology·Jian-Shen ZhaoJalal Hawari
Feb 10, 2006·The Journal of Biological Chemistry·Kentaro MiyazakiSakae Tsuda
Mar 8, 2006·The FEBS Journal·Maria G TozziPiero L Ipata
Nov 7, 2006·Journal of Molecular Graphics & Modelling·Elena PapaleoBjørn O Brandsdal
Jun 28, 2007·Letters in Applied Microbiology·G FeronC Blin-Perrin
Jul 21, 2007·Biotechnology and Applied Biochemistry·Carlo Follo, Ciro Isidoro
Oct 2, 2007·Applied and Environmental Microbiology·Haruhiko SakurabaToshihisa Ohshima
Dec 21, 2007·Acta Crystallographica. Section D, Biological Crystallography·Thomas C TerwilligerPaul D Adams
Aug 19, 2009·Applied Biochemistry and Biotechnology·Jiashi WeiBaorong Lu
Oct 10, 2009·Science·P S G ChainJ C Detter
Jan 9, 2010·Acta Crystallographica. Section D, Biological Crystallography·Vincent B ChenDavid C Richardson
Feb 4, 2010·Acta Crystallographica. Section D, Biological Crystallography·Wolfgang Kabsch
Feb 4, 2010·Acta Crystallographica. Section D, Biological Crystallography·Paul D AdamsPeter H Zwart
Apr 13, 2010·Acta Crystallographica. Section D, Biological Crystallography·P EmsleyK Cowtan
Jan 20, 2011·Proteins·Sebastian Radestock, Holger Gohlke
Feb 1, 2011·Journal of Structural Biology·Matteo Tiberti, Elena Papaleo
Jan 10, 2012·Journal of Biotechnology·Irene Kullartz, Jörg Pietruszka
Feb 14, 2012·Journal of Biotechnology·Prakash C RathiHolger Gohlke
Oct 31, 2012·International Journal of Molecular Sciences·Caroline Struvay, Georges Feller
Dec 31, 2014·BMC Bioinformatics·Sandhya P TiwariNathalie Reuter

❮ Previous
Next ❯

Citations

Feb 12, 2017·ACS Applied Materials & Interfaces·Stefan ReinickeAlexander Böker
Sep 27, 2016·Scientific Reports·Xiao-Fei ZhangYan Feng
Jan 4, 2017·Current Opinion in Structural Biology·Fabrizio Pucci, Marianne Rooman
Mar 30, 2017·Journal of Chemical Theory and Computation·Holger GohlkeKarl-Heinz Baringhaus
Jun 22, 2016·PloS One·Carolin BisterfeldJörg Pietruszka
Nov 11, 2018·The FEBS Journal·Anders O MagnussonWolf-Dieter Fessner
Feb 23, 2019·Biotechnology Journal·Mieke M E HuijbersWillem J H van Berkel
Nov 28, 2018·Archives of Microbiology·Amit S DhaulaniyaDileep Kumar Singh
Oct 5, 2018·Applied Microbiology and Biotechnology·Meera HaridasUlf Hanefeld
Mar 24, 2016·PLoS Computational Biology·Prakash Chandra RathiHolger Gohlke
Dec 7, 2019·The Journal of Biological Chemistry·Taeho KimAlexander F Yakunin
Nov 14, 2020·The EMBO Journal·Gerard H M HuysmansOlga Boudker
May 6, 2021·Journal of Chemical Information and Modeling·Christina NutschelHolger Gohlke
Jul 30, 2021·Journal of Agricultural and Food Chemistry·Lijuan CaoZunxi Huang
Aug 10, 2021·Journal of Chemical Information and Modeling·Daniel BeckerHolger Gohlke
Aug 20, 2021·Applied Microbiology and Biotechnology·Juha RouvinenAnu Koivula
Jan 7, 2020·Journal of Chemical Information and Modeling·Christina NutschelHolger Gohlke
Dec 9, 2021·Extremophiles : Life Under Extreme Conditions·Lorenzo CarréBruno Franzetti

❮ Previous
Next ❯

Methods Mentioned

BETA
X-ray
in silico methods
size exclusion chromatography

Software Mentioned

DERA TM
MolProbity
CNA
MOLREP
refine
DERA
autobuild
DERA PA
AmberTools
phenix

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.