TY - JOUR
T1 - The crystal structure of a homodimeric Pseudomonas glyoxalase I enzyme reveals asymmetric metallation commensurate with half-of-sites activity
AU - Bythell-Douglas, Rohan
AU - Suttisansanee, Uthaiwan
AU - Flematti, Gavin R
AU - Challenor, Michael
AU - Lee, Mihwa
AU - Panjikar, Santosh
AU - Honek, John F
AU - Bond, Charles S
PY - 2015
Y1 - 2015
N2 - 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 Ni2+ ion, whereas the other contains two inactivating Zn2+ ions. Enzymological experiments prompted by the binuclear Zn2+ site identified a novel catalytic property of GloA2. The enzyme can function as a Zn2+ /Co2+ -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.
AB - 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 Ni2+ ion, whereas the other contains two inactivating Zn2+ ions. Enzymological experiments prompted by the binuclear Zn2+ site identified a novel catalytic property of GloA2. The enzyme can function as a Zn2+ /Co2+ -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.
UR - http://onlinelibrary.wiley.com/doi/10.1002/chem.201405402/epdf
U2 - 10.1002/chem.201405402
DO - 10.1002/chem.201405402
M3 - Article
VL - 21
SP - 541
EP - 544
JO - Chemistry - A European Journal
JF - Chemistry - A European Journal
SN - 1521-3765
IS - 2
ER -