Noncysteinyl coordination to the [4Fe-4S]2+ cluster of the DNA repair adenine glycosylase MutY introduced via site-directed mutagenesis. Structural characterization of an unusual histidinyl-coordinated cluster

Biochemistry
Troy E MessickSheila S David

Abstract

The Escherichia coli DNA repair enzyme MutY plays an important role in the recognition and repair of 7,8-dihydro-8-oxo-2'-deoxyguanosine-2'-deoxyadenosine (OG*A) mismatches in DNA. MutY prevents DNA mutations caused by the misincorporation of A opposite OG by catalyzing the deglycosylation of the aberrant adenine. MutY is representative of a unique subfamily of DNA repair enzymes that also contain a [4Fe-4S]2+ cluster, which has been implicated in substrate recognition. Previously, we have used site-directed mutagenesis to individually replace the cysteine ligands to the [4Fe-4S]2+ cluster of E. coli MutY with serine, histidine, or alanine. These experiments suggested that histidine coordination to the iron-sulfur cluster may be accommodated in MutY at position 199. Purification and enzymatic analysis of C199H and C199S forms indicated that these forms behave nearly identical to the WT enzyme. Furthermore, introduction of the C199H mutation in a truncated form of MutY (C199HT) allowed for crystallization and structural characterization of the modified [4Fe-4S] cluster coordination. The C199HT structure showed that histidine coordinated to the iron cluster although comparison to the structure of the WT truncated enzyme indicated...Continue Reading

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Citations

Apr 7, 2005·Current Opinion in Chemical Biology·Olga A Lukianova, Sheila S David
Jul 20, 2011·Proceedings of the National Academy of Sciences of the United States of America·Yasuhiro OhkiKazuyuki Tatsumi
Nov 19, 2013·Journal of Biological Inorganic Chemistry : JBIC : a Publication of the Society of Biological Inorganic Chemistry·Gustav BerggrenMarc Fontecave
Mar 2, 2005·Proceedings of the National Academy of Sciences of the United States of America·Eylon YavinJacqueline K Barton
Oct 16, 2003·Proceedings of the National Academy of Sciences of the United States of America·Elizabeth M BoonJacqueline K Barton
May 2, 2013·Dalton Transactions : an International Journal of Inorganic Chemistry·Marta K BruskaMarkus Reiher
Nov 28, 2015·The FEBS Journal·Carlos H Trasviña-ArenasLuis G Brieba
Jun 30, 2007·Journal of Inorganic Biochemistry·Amie K BoalJacqueline K Barton
Aug 26, 2015·Nucleic Acids Research·Pau Biak SangUmesh Varshney
Aug 8, 2009·FEMS Microbiology Reviews·Bjørn DalhusMagnar Bjørås
Jan 15, 2017·Free Radical Biology & Medicine·Douglas M BandaSheila S David
Sep 19, 2019·Metallomics : Integrated Biometal Science·Paul A Lindahl
May 30, 2020·Journal of the American Chemical Society·Rebekah M B SilvaJacqueline K Barton
Apr 13, 2006·Journal of the American Chemical Society·Sébastien DementinChristophe Léger

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