Structure of uracil-DNA N-glycosylase (UNG) from Vibrio cholerae: mapping temperature adaptation through structural and mutational analysis.

Acta Crystallographica. Section F, Structural Biology and Crystallization Communications
Inger Lin Uttakleiv RaederIngar Leiros

Abstract

The crystal structure of Vibrio cholerae uracil-DNA N-glycosylase (vcUNG) has been determined to 1.5 A resolution. Based on this structure, a homology model of Aliivibrio salmonicida uracil-DNA N-glycosylase (asUNG) was built. A previous study demonstrated that asUNG possesses typical cold-adapted features compared with vcUNG, such as a higher catalytic efficiency owing to increased substrate affinity. Specific amino-acid substitutions in asUNG were suggested to be responsible for the increased substrate affinity and the elevated catalytic efficiency by increasing the positive surface charge in the DNA-binding region. The temperature adaptation of these enzymes has been investigated using structural and mutational analyses, in which mutations of vcUNG demonstrated an increased substrate affinity that more resembled that of asUNG. Visualization of surface potentials revealed a more positive potential for asUNG compared with vcUNG; a modelled double mutant of vcUNG had a potential around the substrate-binding region that was more like that of asUNG, thus rationalizing the results obtained from the kinetic studies.

References

Mar 1, 1991·Acta Crystallographica. Section A, Foundations of Crystallography·T A JonesM Kjeldgaard
Sep 1, 1974·Proceedings of the National Academy of Sciences of the United States of America·T Lindahl
Jul 1, 1997·The Biochemical Journal·H E KrokanG Slupphaug
Feb 27, 1999·Current Opinion in Structural Biology·S S ParikhJ A Tainer
Mar 25, 1999·Acta Crystallographica. Section D, Biological Crystallography·G N MurshudovE J Dodson
May 13, 1999·Bioinformatics·P GouetF Métoz
May 20, 1999·Nature Structural Biology·A PerrakisV S Lamzin
May 11, 2000·Extremophiles : Life Under Extreme Conditions·N J Russell
May 11, 2000·Proceedings of the National Academy of Sciences of the United States of America·S S ParikhJ A Tainer
Dec 29, 2000·Comparative Biochemistry and Physiology. Part B, Biochemistry & Molecular Biology·O LanesN P Willassen
Jan 11, 2001·Biochimica Et Biophysica Acta·P P SheridanJ E Brenchley
Feb 24, 2001·Biotechnology Annual Review·A O SmalåsN P Willassen
Oct 19, 2001·Nature·A R DinnerM Karplus
Oct 27, 2001·Acta Crystallographica. Section D, Biological Crystallography·I LeirosN P Willassen
May 30, 2002·Biochemistry·Yu Lin JiangJames T Stivers
Aug 13, 2002·Philosophical Transactions of the Royal Society of London. Series B, Biological Sciences·Salvino D'AmicoCharles Gerday
Feb 20, 2003·Biochemistry·Yu Lin JiangJames T Stivers
Jul 24, 2003·Acta Crystallographica. Section D, Biological Crystallography·Ingar LeirosNils P Willassen
Sep 1, 1994·Acta Crystallographica. Section D, Biological Crystallography·UNKNOWN Collaborative Computational Project, Number 4
Jul 26, 2005·Acta Crystallographica. Section D, Biological Crystallography·Ingar LeirosSean McSweeney
Jun 8, 2006·Annual Review of Biochemistry·Khawar Sohail Siddiqui, Ricardo Cavicchioli

❮ Previous
Next ❯

Citations

Aug 10, 2010·Acta Crystallographica. Section F, Structural Biology and Crystallization Communications·Prem Singh KaushalM Vijayan
Oct 1, 2011·Comparative Biochemistry and Physiology. Part B, Biochemistry & Molecular Biology·Netsanet Gizaw AssefaElin Moe
Oct 13, 2015·Acta Crystallographica. Section D, Biological Crystallography·Hege Lynum PedersenElin Moe
Jul 7, 2015·Acta Crystallographica. Section D, Biological Crystallography·S M ArifM Vijayan
Aug 2, 2014·Acta Crystallographica. Section D, Biological Crystallography·Netsanet Gizaw AssefaElin Moe
Sep 6, 2012·Acta Crystallographica. Section F, Structural Biology and Crystallization Communications·Akito KawaiShuichi Miyamoto

❮ 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.