Crystal structure of human glyoxalase I_evidence for gene duplication and 3D domain swapping

Cameron, Alexander D.; Olin, B.; Ridderström, Marianne; Mannervik, Bengt; Jones, T. Alwyn

doi:10.1093/emboj/16.12.3386

Cited by 225 publications

(227 citation statements)

References 52 publications

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“…This residue is close to the Glu111 that is replaced by the SNP. The 3D structure of Glo1 with Glu111 has shown that the active Glo1 functions as a dimer with the two zinc atoms, two active sites as well as two glutathione-binding sites formed at the interface [Cameron et al, 1997]. Although, these studies have not shown direct interaction of Glu111 in zinc binding, any chemical interactions that change the 3D structure or disrupt electrostatic bonds are expected to affect enzyme activity.…”

Section: Resultsmentioning

confidence: 99%

Proteomic studies identified a single nucleotide polymorphism in glyoxalase I as autism susceptibility factor

Junaid

Kowal

Barua

et al. 2004

American J of Med Genetics Pt A

144

122

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Autism is a neurodevelopmental disability characterized by deficits in verbal communications, impairments in social interactions, and repetitive behaviors. Several studies have indicated strong involvement of multigenic components in the etiology of autism. Linkage analyses and candidate gene search approaches so far have not identified any reliable susceptibility genes. We are using a proteomic approach to identify protein abnormalities due to aberrant gene expression in autopsied autism brains. In four of eight autism brains, we have found an increase in polarity (more acidic) of glyoxalase I (Glo1) by two-dimensional gel electrophoresis. To identify the molecular change resulting in the shift of Glo1 polarity, we undertook sequencing of GLO1 gene. Direct sequencing of GLO1 gene/mRNA in these brains, has identified a single nucleotide polymorphism (SNP), C419A. The SNP causes an Ala111Glu change in the protein sequence. Population genetics of GLO1 C419A SNP studied in autism (71 samples) and normal and neurological controls (49 samples) showed significantly higher frequency for the A419 (allele frequency 0.6 in autism and 0.4 in controls, one-tailed Fisher's test P < 0.0079). Biochemical measurements have revealed a 38% decrease in Glo1 enzyme activity in autism brains (one-tailed t-test P < 0.026). Western blot analysis has also shown accumulation of advanced glycation end products (AGE's) in autism brains. These data suggest that homozygosity for A419 GLO1 resulting in Glu111 is a predisposing factor in the etiology of autism.

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Section: Resultsmentioning

confidence: 99%

Proteomic studies identified a single nucleotide polymorphism in glyoxalase I as autism susceptibility factor

Junaid

Kowal

Barua

et al. 2004

American J of Med Genetics Pt A

144

122

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“…Domain swapping has been proposed as a possible mechanism for protein aggregation (5). Further, it may be a novel regulatory motif for protein function § (6)(7)(8) as well as a simple evolutionary strategy for evolving oligomers from monomers (9)(10)(11).…”

mentioning

confidence: 99%

Three-dimensional domain swapping in p13suc1 occurs in the unfolded state and is controlled by conserved proline residues

Rousseau¹,

Schymkowitz

Wilkinson

et al. 2001

Proc. Natl. Acad. Sci. U.S.A.

193

216

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CorrectionsBIOCHEMISTRY. For the article ''Differential effects of a centrally acting fatty acid synthase inhibitor in lean and obese mice,'' by Monica V. Kumar, Teruhiko Shimokawa, Tim R. Nagy, and M. Daniel Lane, which appeared in number 4, February 19, 2002, of Proc. Natl. Acad. Sci. USA (99, 1921-1925, the authors note the following. ''Under a licensing agreement between FASgen, Inc., and The Johns Hopkins University, Dr. Lane is entitled to a share of royalty received by the University on sales of products that embody the technology described in this article. (98, 10687-10691; First Published August 28, 2001; 10.1073͞pnas.181354398), the authors note the following. In the Introduction and Discussion of our paper, we failed to reference a recent article by Rousseau et al.(1), which demonstrated that single point mutations can significantly perturb the equilibrium between monomeric and domain-swapped dimeric p13suc1. Rational methods were used to redesign p13suc1 from a fully monomeric protein (dissociation constant of Ϸ900 mM) to a fully dimeric protein (dissociation constant of Ϸ100 nM). Fig. 3 appeared incorrectly. The correct version of the figure and its legend appear below.

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“…Each active site contains one zinc(II) ion, coordinated by 4 amino acids and one molecule of water. The coordination symmetry is close to square pyramidal with 3 amino acids and the water in the plane and the fourth amino acid as the axial ligand (5).…”

mentioning

confidence: 99%

Yeast Glyoxalase I Is a Monomeric Enzyme with Two Active Sites

Frickel¹,

Jemth

Widersten

et al. 2001

Journal of Biological Chemistry

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The tertiary structure of the monomeric yeast glyoxalase I has been modeled based on the crystal structure of the dimeric human glyoxalase I and a sequence alignment of the two enzymes. The model suggests that yeast glyoxalase I has two active sites contained in a single polypeptide. To investigate this, a recombinant expression clone of yeast glyoxalase I was constructed for overproduction of the enzyme in Escherichia coli. Each putative active site was inactivated by site-directed mutagenesis. According to the alignment, glutamate 163 and glutamate 318 in yeast glyoxalase I correspond to glutamate 172 in human glyoxalase I, a Zn(II) ligand and proposed general base in the catalytic mechanism. The residues were each replaced by glutamine and a double mutant containing both mutations was also constructed. Steady-state kinetics and metal analyses of the recombinant enzymes corroborate that yeast glyoxalase I has two functional active sites. The activities of the catalytic sites seem to be somewhat different. The metal ions bound in the active sites are probably one Fe(II) and one Zn(II), but Mn(II) may replace Zn(II). Yeast glyoxalase I appears to be one of the few enzymes that are present as a single polypeptide with two active sites that catalyze the same reaction.Glyoxalase I and glyoxalase II are the two enzymes of the glyoxalase system. Glyoxalase I is an isomerase that catalyzes the formation of S-D-lactoylglutathione from the hemimercaptal adduct that forms nonenzymatically between glutathione and the 2-oxoaldehyde methylglyoxal (Fig. 1). Glyoxalase II then catalyzes the hydrolysis of the glutathione thiolester S-Dlactoylglutathione into reduced glutathione and D-lactate.

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Crystal structure of human glyoxalase I_evidence for gene duplication and 3D domain swapping

Cited by 225 publications

References 52 publications

Proteomic studies identified a single nucleotide polymorphism in glyoxalase I as autism susceptibility factor

Proteomic studies identified a single nucleotide polymorphism in glyoxalase I as autism susceptibility factor

Three-dimensional domain swapping in p13suc1 occurs in the unfolded state and is controlled by conserved proline residues

Yeast Glyoxalase I Is a Monomeric Enzyme with Two Active Sites

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