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Glyoxylate carboligase lacks the canonical active site glutamate of thiamine-dependent enzymes.
- Source :
-
Nature chemical biology [Nat Chem Biol] 2008 Feb; Vol. 4 (2), pp. 113-8. Date of Electronic Publication: 2008 Jan 06. - Publication Year :
- 2008
-
Abstract
- Thiamine diphosphate (ThDP), a derivative of vitamin B1, is an enzymatic cofactor whose special chemical properties allow it to play critical mechanistic roles in a number of essential metabolic enzymes. It has been assumed that all ThDP-dependent enzymes exploit a polar interaction between a strictly conserved glutamate and the N1' of the ThDP moiety. The crystal structure of glyoxylate carboligase challenges this paradigm by revealing that valine replaces the conserved glutamate. Through kinetic, spectroscopic and site-directed mutagenesis studies, we show that although this extreme change lowers the rate of the initial step of the enzymatic reaction, it ensures efficient progress through subsequent steps. Glyoxylate carboligase thus provides a unique illustration of the fine tuning between catalytic stages imposed during evolution on enzymes catalyzing multistep processes.
- Subjects :
- Binding Sites
Carboxy-Lyases genetics
Carboxylic Acids chemistry
Carboxylic Acids metabolism
Circular Dichroism
Crystallography, X-Ray
Escherichia coli enzymology
Escherichia coli genetics
Kinetics
Models, Molecular
Mutation genetics
Phosphates chemistry
Protein Structure, Tertiary
Thiamine analogs & derivatives
Thiazoles chemistry
Thiazoles metabolism
Valine genetics
Valine metabolism
Carboxy-Lyases chemistry
Carboxy-Lyases metabolism
Glutamates chemistry
Glutamates metabolism
Thiamine chemistry
Thiamine metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 1552-4469
- Volume :
- 4
- Issue :
- 2
- Database :
- MEDLINE
- Journal :
- Nature chemical biology
- Publication Type :
- Academic Journal
- Accession number :
- 18176558
- Full Text :
- https://doi.org/10.1038/nchembio.62