Modulating glyoxalase i metal selectivity by deletional mutagenesis: Underlying structural factors contributing to nickel activation profiles
© 2015 The Royal Society of Chemistry. Metabolically produced methylglyoxal is a cytotoxic compound that can lead to covalent modification of cellular DNA, RNA and protein. One pathway to detoxify this compound is via the glyoxalase enzyme system. The first enzyme of this detoxification system, glyo...
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th-mahidol.354802018-11-23T17:23:42Z Modulating glyoxalase i metal selectivity by deletional mutagenesis: Underlying structural factors contributing to nickel activation profiles Uthaiwan Suttisansanee Yanhong Ran Kadia Y. Mullings Nicole Sukdeo John F. Honek University of Waterloo Mahidol University Jinan University GreenLight Biosciences University of Northern British Columbia Biochemistry, Genetics and Molecular Biology Chemistry Materials Science © 2015 The Royal Society of Chemistry. Metabolically produced methylglyoxal is a cytotoxic compound that can lead to covalent modification of cellular DNA, RNA and protein. One pathway to detoxify this compound is via the glyoxalase enzyme system. The first enzyme of this detoxification system, glyoxalase I (GlxI), can be divided into two classes according to its metal activation profile, a Zn2+-activated class and a Ni2+-activated class. In order to elucidate some of the key structural features required for selective metal activation by these two classes of GlxI, deletional mutagenesis was utilized to remove, in a step-wise fashion, a key α-helix (residues 73-87) and two small loop regions (residues 99-103 and 111-114) from the Zn2+-activated Pseudomonas aeruginosa GlxI (GloA3) in order to mimic the smaller Ni2+-activated GlxI (GloA2) from the same organism. This approach was observed to clearly shift the metal activation profile of a Zn2+-activated class GlxI into a Ni2+-activated class GlxI enzyme. The α-helix structural component was found to contribute significantly toward GlxI metal specificity, while the two small loop regions were observed to play a more crucial role in the magnitude of the enzymatic activity. The current study should provide additional information on the fundamental relationship of protein structure to metal selectivity in these metalloenzymes. 2018-11-23T09:44:31Z 2018-11-23T09:44:31Z 2015-04-01 Article Metallomics. Vol.7, No.4 (2015), 605-612 10.1039/c4mt00299g 1756591X 17565901 2-s2.0-84927646710 https://repository.li.mahidol.ac.th/handle/123456789/35480 Mahidol University SCOPUS https://www.scopus.com/inward/record.uri?partnerID=HzOxMe3b&scp=84927646710&origin=inward |
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Biochemistry, Genetics and Molecular Biology Chemistry Materials Science Uthaiwan Suttisansanee Yanhong Ran Kadia Y. Mullings Nicole Sukdeo John F. Honek Modulating glyoxalase i metal selectivity by deletional mutagenesis: Underlying structural factors contributing to nickel activation profiles |
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© 2015 The Royal Society of Chemistry. Metabolically produced methylglyoxal is a cytotoxic compound that can lead to covalent modification of cellular DNA, RNA and protein. One pathway to detoxify this compound is via the glyoxalase enzyme system. The first enzyme of this detoxification system, glyoxalase I (GlxI), can be divided into two classes according to its metal activation profile, a Zn2+-activated class and a Ni2+-activated class. In order to elucidate some of the key structural features required for selective metal activation by these two classes of GlxI, deletional mutagenesis was utilized to remove, in a step-wise fashion, a key α-helix (residues 73-87) and two small loop regions (residues 99-103 and 111-114) from the Zn2+-activated Pseudomonas aeruginosa GlxI (GloA3) in order to mimic the smaller Ni2+-activated GlxI (GloA2) from the same organism. This approach was observed to clearly shift the metal activation profile of a Zn2+-activated class GlxI into a Ni2+-activated class GlxI enzyme. The α-helix structural component was found to contribute significantly toward GlxI metal specificity, while the two small loop regions were observed to play a more crucial role in the magnitude of the enzymatic activity. The current study should provide additional information on the fundamental relationship of protein structure to metal selectivity in these metalloenzymes. |
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University of Waterloo |
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University of Waterloo Uthaiwan Suttisansanee Yanhong Ran Kadia Y. Mullings Nicole Sukdeo John F. Honek |
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Article |
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Uthaiwan Suttisansanee Yanhong Ran Kadia Y. Mullings Nicole Sukdeo John F. Honek |
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Uthaiwan Suttisansanee |
title |
Modulating glyoxalase i metal selectivity by deletional mutagenesis: Underlying structural factors contributing to nickel activation profiles |
title_short |
Modulating glyoxalase i metal selectivity by deletional mutagenesis: Underlying structural factors contributing to nickel activation profiles |
title_full |
Modulating glyoxalase i metal selectivity by deletional mutagenesis: Underlying structural factors contributing to nickel activation profiles |
title_fullStr |
Modulating glyoxalase i metal selectivity by deletional mutagenesis: Underlying structural factors contributing to nickel activation profiles |
title_full_unstemmed |
Modulating glyoxalase i metal selectivity by deletional mutagenesis: Underlying structural factors contributing to nickel activation profiles |
title_sort |
modulating glyoxalase i metal selectivity by deletional mutagenesis: underlying structural factors contributing to nickel activation profiles |
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2018 |
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https://repository.li.mahidol.ac.th/handle/123456789/35480 |
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1763489050491092992 |