title: Crystal structure of Staphylococcus aureus Zn-glyoxalase I: new subfamily of glyoxalase I family.
abstract: 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.
authors.affiliation: a Institute of Protein Research , Russian Academy of Sciences , Pushchino 142290 , Moscow Region , Russia.
authors.forename: Yuri N
authors.initials: YN
authors.lastname: Chirgadze
authors.affiliation: a Institute of Protein Research , Russian Academy of Sciences , Pushchino 142290 , Moscow Region , Russia.
authors.forename: Eugenia A
authors.initials: EA
authors.lastname: Boshkova
authors.affiliation: b Advanced Photon Source, Argonne National Laboratory , Hauptman-Woodward Medical Research Institute, IMCA-CAT , Argonne , IL 60439 , USA.
authors.forename: Kevin P
authors.initials: KP
authors.lastname: Battaile
authors.affiliation: c Department of Biochemistry , University of Cambridge , Cambridge CB2 1GA , UK.
authors.forename: Vitor G
authors.initials: VG
authors.lastname: Mendes
authors.affiliation: d Campbell Family Cancer Research Institute, Ontario Cancer Institute , Princess Margaret Hospital, University Health Network , Toronto , Ontario M5G 2C4 , Canada.
authors.forename: Robert
authors.initials: R
authors.lastname: Lam
authors.affiliation: d Campbell Family Cancer Research Institute, Ontario Cancer Institute , Princess Margaret Hospital, University Health Network , Toronto , Ontario M5G 2C4 , Canada.
authors.forename: Tiffany S Y
authors.initials: TSY
authors.lastname: Chan
authors.affiliation: d Campbell Family Cancer Research Institute, Ontario Cancer Institute , Princess Margaret Hospital, University Health Network , Toronto , Ontario M5G 2C4 , Canada.
authors.forename: Vladimir
authors.initials: V
authors.lastname: Romanov
authors.affiliation: d Campbell Family Cancer Research Institute, Ontario Cancer Institute , Princess Margaret Hospital, University Health Network , Toronto , Ontario M5G 2C4 , Canada.|e Department of Biochemistry , University of Toronto , Toronto , Ontario M5S 1A8 , Canada.|f Department of Molecular Genetics , University of Toronto , Toronto , Ontario M5S 1A8 , Canada.|g Department of Medical Biophysics , University of Toronto , Toronto , Ontario M5S 1A8 , Canada.
authors.forename: Emil F
authors.initials: EF
authors.lastname: Pai
authors.affiliation: d Campbell Family Cancer Research Institute, Ontario Cancer Institute , Princess Margaret Hospital, University Health Network , Toronto , Ontario M5G 2C4 , Canada.|h Department of Pharmacology and Toxicology , University of Toronto , Toronto , Ontario M5S 1A8, Canada.|i X-CHIP Technologies Inc. , Toronto , Ontario , Canada.
authors.forename: Nickolay Y
authors.initials: NY
authors.lastname: Chirgadze
mesh_terms: D000595:Amino Acid Sequence / Q000235:genetics; D001665:Binding Sites; D002384:Catalysis; D020134:Catalytic Domain; D018360:Crystallography, X-Ray; D006801:Humans; D007791:Lactoylglutathione Lyase / Q000737:chemistry* / Q000235:genetics; D008958:Models, Molecular; D011487:Protein Conformation; D013211:Staphylococcus aureus / Q000737:chemistry* / Q000201:enzymology / Q000472:pathogenicity; D015032:Zinc / Q000737:chemistry*
chemical_list: C000597196:GLO1 protein, human; D007791:Lactoylglutathione Lyase; D015032:Zinc
keywords: glyoxalase I; metalloprotein; pathogen; subfamily