The crystal structure of human endonuclease VIII-like 1 (NEIL1) reveals a zincless finger motif required for glycosylase activity

Proceedings of the National Academy of Sciences of the United States of America
Sylvie DoubliéSusan S Wallace

Abstract

In prokaryotes, two DNA glycosylases recognize and excise oxidized pyrimidines: endonuclease III (Nth) and endonuclease VIII (Nei). The oxidized purine 8-oxoguanine, on the other hand, is recognized by Fpg (also known as MutM), a glycosylase that belongs to the same family as Nei. The recent availability of the human genome sequence allowed the identification of three human homologs of Escherichia coli Nei. We report here the crystal structure of a human Nei-like (NEIL) enzyme, NEIL1. The structure of NEIL1 exhibits the same overall fold as E. coli Nei, albeit with an unexpected twist. Sequence alignments had predicted that NEIL1 would lack a zinc finger, and it was therefore expected to use a different DNA-binding motif instead. Our structure revealed that, to the contrary, NEIL1 contains a structural motif composed of two antiparallel beta-strands that mimics the antiparallel beta-hairpin zinc finger found in other Fpg/Nei family members but lacks the loops that harbor the zinc-binding residues and, therefore, does not coordinate zinc. This "zincless finger" appears to be required for NEIL1 activity, because mutating a very highly conserved arginine within this motif greatly reduces the glycosylase activity of the enzyme.

References

Mar 1, 1991·Acta Crystallographica. Section A, Foundations of Crystallography·T A JonesM Kjeldgaard
Jun 1, 1991·Proceedings of the National Academy of Sciences of the United States of America·J TchouS Nishimura
Jul 1, 1989·Proceedings of the National Academy of Sciences of the United States of America·T R O'Connor, J Laval
Feb 8, 1994·Biochemistry·R J MelamedeS S Wallace
Jul 1, 1997·The Biochemical Journal·H E KrokanG Slupphaug
Sep 1, 1997·Nucleic Acids Research·S F AltschulD J Lipman
Oct 6, 1997·Science·B I Dahiyat, S L Mayo
Feb 21, 1998·Nucleic Acids Research·L Holm, C Sander
Jan 24, 1998·The Journal of Biological Chemistry·D JiangS S Wallace
May 23, 1998·The Journal of Biological Chemistry·A A PurmalS S Wallace
Oct 3, 1998·Acta Crystallographica. Section D, Biological Crystallography·A T BrüngerG L Warren
Mar 25, 1999·Acta Crystallographica. Section D, Biological Crystallography·T C Terwilliger, J Berendzen
Apr 1, 2000·The Journal of Biological Chemistry·O M Sidorkina, J Laval
Jun 1, 2000·Journal of the American Society for Mass Spectrometry·R A RiegerC R Iden
Jun 29, 2000·Annual Review of Biochemistry·A K McCulloughR S Lloyd
Sep 22, 2001·Structure·R Sarma
Mar 21, 2002·Proceedings of the National Academy of Sciences of the United States of America·Tapas K HazraSankar Mitra
Mar 26, 2002·The Journal of Biological Chemistry·Rotem GilboaGil Shoham
Jun 11, 2002·Nature Structural Biology·J Christopher Fromme, Gregory L Verdine
Jun 28, 2002·Free Radical Biology & Medicine·Susan S Wallace
Jul 5, 2002·The Journal of Biological Chemistry·Tapas K HazraTadahide Izumi
Jul 30, 2002·The Journal of Biological Chemistry·R Abhilash KumarVadim N Gladyshev
Aug 9, 2002·Molecular and Cellular Biology·Maria T A OcampoGeorge W Teebor
Aug 30, 2002·The Journal of Biological Chemistry·Masashi TakaoAkira Yasui
Oct 29, 2002·The Journal of Biological Chemistry·Rhoderick H Elder, Grigory L Dianov
Dec 24, 2002·Acta Crystallographica. Section A, Foundations of Crystallography·V A Blatov, A P Shevchenko
Apr 18, 2003·Frontiers in Bioscience : a Journal and Virtual Library·David M WilsonDaniel R McNeill
Apr 26, 2003·DNA Repair·Susan S WallaceJeffrey P Bond
Apr 26, 2003·DNA Repair·Thomas A RosenquistArthur P Grollman
Aug 2, 2003·DNA Repair·Dmitry O ZharkovArthur P Grollman

❮ Previous
Next ❯

Citations

Aug 18, 2010·Cellular and Molecular Life Sciences : CMLS·Muralidhar L HegdeSankar Mitra
Jun 9, 2005·Mutation Research·Joy L HuffmanJohn A Tainer
Jun 25, 2008·The British Journal of Nutrition·Siegfried KnasmüllerKarl-Heinz Wagner
Apr 9, 2011·Biochemistry·Jennifer L Przybylski, Stacey D Wetmore
Jun 22, 2007·Nature·Sheila S DavidSucharita Kundu
Nov 12, 2010·Proceedings of the National Academy of Sciences of the United States of America·Jongchan YeoPeter A Beal
Jul 25, 2009·The Journal of Biological Chemistry·Kayo ImamuraSylvie Doublié
Sep 1, 2005·Nucleic Acids Research·Jason L ParsonsGrigory L Dianov
Aug 24, 2007·Nucleic Acids Research·Sophie Couvé-PrivatMurat K Saparbaev
Nov 18, 2009·Biochemistry. Biokhimii︠a︡·I R GrinD O Zharkov
May 17, 2011·Biochemistry. Biokhimii︠a︡·I R Grin, D O Zharkov
Nov 28, 2015·The FEBS Journal·Carlos H Trasviña-ArenasLuis G Brieba
Jan 1, 2013·Mutation Research·Minmin LiuSusan S Wallace
Aug 4, 2012·DNA Repair·Erik Sebastian VikBjørn Dalhus
Feb 9, 2012·Mechanisms of Ageing and Development·Muralidhar L HegdeBartosz Szczesny
Dec 14, 2011·Mutation Research·Valeria SimonelliEugenia Dogliotti
Apr 19, 2011·Gene·B C ResendeD O Lopes
Sep 15, 2010·DNA Repair·Rachel V WoodruffGraham C Walker
Mar 30, 2010·DNA Repair·Venkateswarlu PopuriVilhelm A Bohr
Aug 12, 2008·Free Radical Biology & Medicine·Miral DizdarogluPawel Jaruga
Oct 15, 2013·Environmental and Molecular Mutagenesis·Susan S Wallace
Aug 3, 2014·Biochimica Et Biophysica Acta·Alexandra A KuznetsovaOlga S Fedorova
Mar 11, 2015·Journal of Cellular Biochemistry·Aishwarya Prakash, Sylvie Doublié
Oct 15, 2013·DNA Repair·Aishwarya PrakashSylvie Doublié

❮ 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.