|
type |
Journal Article |
authors |
Garrido-Franco, M.; Ehlert, S.; Messerschmidt, A.; Marinkovic, S.; Huber, R.; Laber, B.; Bourenkov, G. P.; Clausen, T. |
title |
Structure and function of threonine synthase from yeast |
journal |
J Biol Chem |
Activity |
4.2.3.1 |
Family |
4.2.3.1 |
sel |
selected |
ui |
11756443 |
year |
(2002) |
volume |
277 |
number |
14 |
pages |
12396-405 |
| |
keywords |
Binding Sites |
abstract |
Threonine synthase catalyzes the final step of threonine biosynthesis, the pyridoxal 5'-phosphate (PLP)-dependent conversion of O- phosphohomoserine into threonine and inorganic phosphate. Threonine is an essential nutrient for mammals, and its biosynthetic machinery is restricted to bacteria, plants, and fungi; therefore, threonine synthase represents an interesting pharmaceutical target. The crystal structure of threonine synthase from Saccharomyces cerevisiae has been solved at 2.7 A resolution using multiwavelength anomalous diffraction. The structure reveals a monomer as active unit, which is subdivided into three distinct domains: a small N-terminal domain, a PLP-binding domain that covalently anchors the cofactor and a so-called large domain, which contains the main of the protein body. All three domains show the typical open alpha/beta architecture. The cofactor is bound at the interface of all three domains, buried deeply within a wide canyon that penetrates the whole molecule. Based on structural alignments with related enzymes, an enzyme-substrate complex was modeled into the active site of yeast threonine synthase, which revealed essentials for substrate binding and catalysis. Furthermore, the comparison with related enzymes of the beta-family of PLP-dependent enzymes indicated structural determinants of the oligomeric state and thus rationalized for the first time how a PLP enzyme acts in monomeric form. |
last changed |
2009/01/09 14:26 |
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