| Structural highlights
Function
DHOM_SULTO Catalyzes the conversion of L-aspartate-beta-semialdehyde (L-Asa) to L-homoserine (L-Hse), the third step in the biosynthesis of threonine and methionine from aspartate.[1] [2] [3]
Publication Abstract from PubMed
When overexpressed as an immature enzyme in the mesophilic bacterium Escherichia coli, recombinant homoserine dehydrogenase from the hyperthermophilic archaeon Sulfurisphaera tokodaii (StHSD) was markedly activated by heat treatment. Both the apo- and holo-forms of the immature enzyme were successively crystallized, and the two structures were determined. Comparison among the structures of the immature enzyme and previously reported structures of mature enzymes revealed that a conformational change in a flexible part (residues 160-190) of the enzyme, which encloses substrates within the substrate-binding pocket, is smaller in the immature enzyme. The immature enzyme, but not the mature enzyme, formed a complex that included NADP(+), despite its absence during crystallization. This indicates that the opening to the substrate-binding pocket in the immature enzyme is not sufficient for substrate-binding, efficient catalytic turnover or release of NADP(+). Thus, specific conformational changes within the catalytic region appear to be responsible for heat-induced activation.
Conformational changes in the catalytic region are responsible for heat-induced activation of hyperthermophilic homoserine dehydrogenase.,Kubota T, Kurihara E, Watanabe K, Ogata K, Kaneko R, Goto M, Ohshima T, Yoshimune K Commun Biol. 2022 Jul 14;5(1):704. doi: 10.1038/s42003-022-03656-7. PMID:35835834[4]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Tomonaga Y, Kaneko R, Goto M, Ohshima T, Yoshimune K. Structural insight into activation of homoserine dehydrogenase from the archaeon Sulfolobus tokodaii via reduction. Biochem Biophys Rep. 2015 Jul 15;3:14-17. doi: 10.1016/j.bbrep.2015.07.006., eCollection 2015 Sep. PMID:29124164 doi:https://dx.doi.org/10.1016/j.bbrep.2015.07.006
- ↑ Ogata K, Yajima Y, Nakamura S, Kaneko R, Goto M, Ohshima T, Yoshimune K. Inhibition of homoserine dehydrogenase by formation of a cysteine-NAD covalent complex. Sci Rep. 2018 Apr 10;8(1):5749. doi: 10.1038/s41598-018-24063-1. PMID:29636528 doi:https://dx.doi.org/10.1038/s41598-018-24063-1
- ↑ Kubota T, Kurihara E, Watanabe K, Ogata K, Kaneko R, Goto M, Ohshima T, Yoshimune K. Conformational changes in the catalytic region are responsible for heat-induced activation of hyperthermophilic homoserine dehydrogenase. Commun Biol. 2022 Jul 14;5(1):704. doi: 10.1038/s42003-022-03656-7. PMID:35835834 doi:https://dx.doi.org/10.1038/s42003-022-03656-7
- ↑ Kubota T, Kurihara E, Watanabe K, Ogata K, Kaneko R, Goto M, Ohshima T, Yoshimune K. Conformational changes in the catalytic region are responsible for heat-induced activation of hyperthermophilic homoserine dehydrogenase. Commun Biol. 2022 Jul 14;5(1):704. doi: 10.1038/s42003-022-03656-7. PMID:35835834 doi:https://dx.doi.org/10.1038/s42003-022-03656-7
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