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The Crystal Structure of a Homodimeric Pseudomonas Glyoxalase I Enzyme Reveals Asymmetric Metallation Commensurate with Half‐of‐Sites Activity
Author(s) -
BythellDouglas Rohan,
Suttisansanee Uthaiwan,
Flematti Gavin R.,
Challenor Michael,
Lee Mihwa,
Panjikar Santosh,
Honek John F.,
Bond Charles S.
Publication year - 2015
Publication title -
chemistry – a european journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.687
H-Index - 242
eISSN - 1521-3765
pISSN - 0947-6539
DOI - 10.1002/chem.201405402
Subject(s) - active site , enzyme , chemistry , lactoylglutathione lyase , hydrolase , metal , stereochemistry , crystal structure , crystallography , binding site , metal ions in aqueous solution , biochemistry , glutathione , organic chemistry
The Zn inactive class of glyoxalase I (Glo1) metalloenzymes are typically homodimeric with two metal‐dependent active sites. While the two active sites share identical amino acid composition, this class of enzyme is optimally active with only one metal per homodimer. We have determined the X‐ray crystal structure of GloA2, a Zn inactive Glo1 enzyme from Pseudomonas aeruginosa . The presented structures exhibit an unprecedented metal‐binding arrangement consistent with half‐of‐sites activity: one active site contains a single activating Ni 2+ ion, whereas the other contains two inactivating Zn 2+ ions. Enzymological experiments prompted by the binuclear Zn 2+ site identified a novel catalytic property of GloA2. The enzyme can function as a Zn 2+ /Co 2+ ‐dependent hydrolase, in addition to its previously determined glyoxalase I activity. The presented findings demonstrate that GloA2 can accommodate two distinct metal‐binding arrangements simultaneously, each of which catalyzes a different reaction.