Mank N J, Pote S, Majorek K A, Arnette A K, Klapper V G, Hurlburt B K, Chruszcz M
Department of Chemistry and Biochemistry, University of South Carolina, 631 Sumter Street, Columbia, SC 29208, USA.
Department of Molecular Physiology and Biological Physics, University of Virginia, PO Box 800736, Charlottesville, VA 22908, USA.
Acta Crystallogr F Struct Biol Commun. 2018 Jan 1;74(Pt 1):14-22. doi: 10.1107/S2053230X17017241.
Aspartate β-semialdehyde dehydrogenase (ASADH) is an enzyme involved in the diaminopimelate pathway of lysine biosynthesis. It is essential for the viability of many pathogenic bacteria and therefore has been the subject of considerable research for the generation of novel antibiotic compounds. This manuscript describes the first structure of ASADH from Francisella tularensis, the causative agent of tularemia and a potential bioterrorism agent. The structure was determined at 2.45 Å resolution and has a similar biological assembly to other bacterial homologs. ASADH is known to be dimeric in bacteria and have extensive interchain contacts, which are thought to create a half-sites reactivity enzyme. ASADH from higher organisms shows a tetrameric oligomerization, which also has implications for both reactivity and regulation. This work analyzes the apo form of F. tularensis ASADH, as well as the binding of the enzyme to its cofactor NADP.
天冬氨酸β-半醛脱氢酶（ASADH）是一种参与赖氨酸生物合成中二氨基庚二酸途径的酶。它对许多致病细菌的生存能力至关重要，因此一直是新型抗生素化合物研发的大量研究对象。本手稿描述了来自土拉热弗朗西斯菌的ASADH的首个结构，土拉热弗朗西斯菌是兔热病的病原体和一种潜在的生物恐怖主义制剂。该结构在2.45 Å分辨率下确定，并且具有与其他细菌同源物相似的生物组装。已知ASADH在细菌中是二聚体，具有广泛的链间接触，这被认为会产生一种半位点反应性酶。来自高等生物的ASADH显示出四聚体寡聚化，这对反应性和调节也有影响。这项工作分析了土拉热弗朗西斯菌ASADH的无辅基形式，以及该酶与辅因子NADP的结合。
