Dahal Gopal P, Viola Ronald E
Department of Chemistry and Biochemistry, University of Toledo, Toledo, OH 43606, USA.
Acta Crystallogr F Struct Biol Commun. 2017 Jan 1;73(Pt 1):36-44. doi: 10.1107/S2053230X16020070.
Aspartate-semialdehyde dehydrogenase (ASADH) functions at a critical junction in the aspartate biosynthetic pathway and represents a validated target for antimicrobial drug design. This enzyme catalyzes the NADPH-dependent reductive dephosphorylation of β-aspartyl phosphate to produce the key intermediate aspartate semialdehyde. The absence of this entire pathway in humans and other mammals will allow the selective targeting of pathogenic microorganisms for antimicrobial development. Here, the X-ray structure of a new form of ASADH from the pathogenic fungal species Aspergillus fumigatus has been determined. The overall structure of this enzyme is similar to those of its bacterial orthologs, but there are some critical differences both in biological assembly and in secondary-structural features that can potentially be exploited for the development of species-selective drugs with selective toxicity against infectious fungal organisms.
天冬氨酸半醛脱氢酶（ASADH）在天冬氨酸生物合成途径的关键节点发挥作用，是抗菌药物设计的一个已验证靶点。该酶催化β-天冬氨酰磷酸的NADPH依赖性还原脱磷酸反应，生成关键中间体天冬氨酸半醛。人类和其他哺乳动物缺乏这一完整途径，这使得在抗菌药物研发中能够选择性地靶向致病微生物。在此，已确定了致病真菌烟曲霉中一种新型ASADH的X射线结构。该酶的整体结构与其细菌直系同源物相似，但在生物组装和二级结构特征方面存在一些关键差异，这些差异有可能被用于开发对感染性真菌具有选择性毒性的物种选择性药物。
