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J Biomol Struct Dyn. 2018 Feb;36(2):376-386. doi: 10.1080/07391102.2016.1278038. Epub 2017 Jan 16.

Crystal structure of Staphylococcus aureus Zn-glyoxalase I: new subfamily of glyoxalase I family.

Author information

1
a Institute of Protein Research , Russian Academy of Sciences , Pushchino 142290 , Moscow Region , Russia.
2
b Advanced Photon Source, Argonne National Laboratory , Hauptman-Woodward Medical Research Institute, IMCA-CAT , Argonne , IL 60439 , USA.
3
c Department of Biochemistry , University of Cambridge , Cambridge CB2 1GA , UK.
4
d Campbell Family Cancer Research Institute, Ontario Cancer Institute , Princess Margaret Hospital, University Health Network , Toronto , Ontario M5G 2C4 , Canada.
5
e Department of Biochemistry , University of Toronto , Toronto , Ontario M5S 1A8 , Canada.
6
f Department of Molecular Genetics , University of Toronto , Toronto , Ontario M5S 1A8 , Canada.
7
g Department of Medical Biophysics , University of Toronto , Toronto , Ontario M5S 1A8 , Canada.
8
h Department of Pharmacology and Toxicology , University of Toronto , Toronto , Ontario M5S 1A8, Canada.
9
i X-CHIP Technologies Inc. , Toronto , Ontario , Canada.

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.

KEYWORDS:

glyoxalase I; metalloprotein; pathogen; subfamily

PMID:
28034013
DOI:
10.1080/07391102.2016.1278038
[Indexed for MEDLINE]

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