Plasmodium falciparum Apn1 homolog is a mitochondrial base excision repair protein with restricted enzymatic functions

The FEBS Journal
Anupama TiwariSaman Habib

Abstract

The malaria parasite carries two organelles, the apicoplast and mitochondrion, whose DNA genomes must be maintained for optimal function and parasite survival under genotoxic stress. DNA repair mechanism(s) operative within these organelles were explored by mining the Plasmodium falciparum nuclear genome for sequences encoding proteins of major DNA repair pathways with predicted targeting to either organelle. Of the panel of enzymes identified for base excision repair (BER), we characterized the apurinic/apyrimidinic (AP) endonuclease PfApn1-an EndoIV whose homolog is not known in humans. PfApn1 targeted to the mitochondrion and functioned as an AP endonuclease requiring both Zn2+ and Mn2+ ions for maximal activity. Mutation of the critical third metal-binding site residue H542 resulted in the loss of Mn2+ (but not Zn2+ ) binding indicating that Mn2+ bound PfApn1 at this site; this was further supported by molecular dynamic simulation. CD spectra analysis further showed requirement of both metal ions for the attainment of PfApn1 β-strand-rich optimal conformation. PfApn1 also functioned as a 3'-phosphatase that would enable removal of 3'-blocks for DNA polymerase activity during BER. Interestingly, unlike Escherichia coli and y...Continue Reading

References

Apr 12, 1994·Proceedings of the National Academy of Sciences of the United States of America·E BabiychukD Inzé
Dec 5, 1993·Journal of Molecular Biology·A Sali, T L Blundell
Aug 16, 1996·Journal of Molecular Biology·R J WilsonD H Williamson
May 12, 2000·The Journal of Biological Chemistry·I UnkL Prakash
Nov 22, 2002·The Journal of Biological Chemistry·Sinéad M KerinsTommie V McCarthy
Feb 1, 2003·Science·Bernardo J FothGeoffrey I McFadden
Jun 5, 2003·The Journal of Biological Chemistry·Anandi S KarumbatiThomas E Wilson
Nov 6, 2003·Molecular and Biochemical Parasitology·Andreas BenderGisbert Schneider
Dec 3, 2003·Trends in Genetics : TIG·David J Conway
Jul 21, 2004·Molecular Cell·Lee WiederholdTapas K Hazra
Jun 1, 2005·Molecular and Biochemical Parasitology·Fiona SeowMichael P Barrett
Nov 4, 2005·Current Topics in Microbiology and Immunology·A B Vaidya, M W Mather
Feb 14, 2006·Proceedings of the National Academy of Sciences of the United States of America·Alexander A IshchenkoMurat K Saparbaev
Apr 18, 2006·Nucleic Acids Research·Ranajoy ChattopadhyaySankar Mitra
Jan 24, 2007·Proceedings of the National Academy of Sciences of the United States of America·Ivaylo IvanovJ Andrew McCammon
Jun 15, 2007·Nucleic Acids Research·Takashi Ishida, Kengo Kinoshita
Aug 11, 2007·Molecular and Biochemical Parasitology·Jeffrey S BuguliskisTheodore F Taraschi
Sep 18, 2007·Journal of Molecular Biology·Antonio E VidalDolores González-Pacanowska
Oct 12, 2007·Molecular and Biochemical Parasitology·Louis J CastaTheodore F Taraschi
Apr 15, 2008·Nature Structural & Molecular Biology·Elsa D GarcinJohn A Tainer
May 3, 2008·Trends in Parasitology·Erica L Dahl, Philip J Rosenthal
Jan 21, 2009·Methods in Enzymology·Brian J AndersonJoel F Schildbach
Feb 7, 2009·Environmental and Molecular Mutagenesis·Karina Acevedo-TorresCarlos A Torres-Ramos
Feb 17, 2009·Current Biology : CB·Giel G van DoorenBoris Striepen
Apr 18, 2009·The Journal of Biological Chemistry·Benjamin L Gutman, Krishna K Niyogi
Oct 19, 2010·Biochimica Et Biophysica Acta·Pierre BoeschAndré Dietrich
Feb 19, 2011·Parasitology International·Kenji HikosakaKazuyuki Tanabe
Mar 9, 2011·PLoS Pathogens·Franck PrugnolleFrançois Renaud
Nov 15, 2011·Molecular and Biochemical Parasitology·Mohammed TariqueRenu Tuteja
May 3, 2013·Cold Spring Harbor Perspectives in Biology·Mikhail AlexeyevSusan LeDoux
May 7, 2013·Cold Spring Harbor Perspectives in Biology·Akira Yasui
Apr 20, 2014·Malaria Journal·Thidarat SuksangplengPorntip Chavalitshewinkoon-Petmitr

❮ 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.