Crystal structure of Staphylococcus aureus Zn-glyoxalase I: new subfamily of glyoxalase I family
- Institute of Protein Research, Russian Academy of Sciences, Pushchino 142290, Moscow Region, Russia
- Advanced Photon Source, Argonne National Laboratory, Hauptman–Woodward Medical Research Institute, IMCA-CAT, Argonne, IL 60439, USA
- Department of Biochemistry, University of Cambridge, Cambridge CB2 1GA, UK
- Campbell Family Cancer Research Institute, Ontario Cancer Institute, Princess Margaret Hospital, University Health Network, Toronto, Ontario M5G 2C4, Canada
- Campbell Family Cancer Research Institute, Ontario Cancer Institute, Princess Margaret Hospital, University Health Network, Toronto, Ontario M5G 2C4, Canada; Department of Biochemistry, University of Toronto, Toronto, Ontario M5S 1A8, Canada; Department of Molecular Genetics, University of Toronto, Toronto, Ontario M5S 1A8, Canada; Department of Medical Biophysics, University of Toronto, Toronto, Ontario M5S 1A8, Canada
- Campbell Family Cancer Research Institute, Ontario Cancer Institute, Princess Margaret Hospital, University Health Network, Toronto, Ontario M5G 2C4, Canada; Department of Pharmacology and Toxicology, University of Toronto, Toronto, Ontario M5S 1A8, Canada; X-CHIP Technologies Inc., Toronto, Ontario, Canada
The crystal structures of protein SA0856 from Staphylococcus aureus in its apo-form and in complex with a Zn2+-ion have been presented. The 152 amino acid protein consists of two similar domains with α + β topology. In both crystalline state and in solution, the protein forms a dimer with monomers related by a twofold pseudo-symmetry rotation axis. A sequence homology search identified the protein as a member of the structural family Glyoxalase I. We have shown that the enzyme possesses glyoxalase I activity in the presence of Zn2+, Mg2+, Ni2+, and Co2+, in this order of preference. Sequence and structure comparisons revealed that human glyoxalase I should be assigned to a subfamily A, while S. aureus glyoxalase I represents a new subfamily B, which includes also proteins from other bacteria. Both subfamilies have a similar protein chain fold but rather diverse sequences. The active sites of human and staphylococcus glyoxalases I are also different: the former contains one Zn-ion per chain; the latter incorporates two of these ions. In the active site of SA0856, the first Zn-ion is well coordinated by His58, Glu60 from basic molecule and Glu40*, His44* from adjacent symmetry-related molecule. The second Zn3-ion is coordinated only by residue His143 from protein molecule and one acetate ion. We suggest that only single Zn1-ion plays the role of catalytic center. The newly found differences between the two subfamilies could guide the design of new drugs against S. aureus, an important pathogenic micro-organism.
- Research Organization:
- Argonne National Lab. (ANL), Argonne, IL (United States). Advanced Photon Source (APS)
- Sponsoring Organization:
- USDOE Office of Science (SC)
- OSTI ID:
- 1418025
- Journal Information:
- Journal of Biomolecular Structure and Dynamics, Vol. 36, Issue 2; ISSN 0739-1102
- Country of Publication:
- United States
- Language:
- ENGLISH
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