Dahal Gopal, Viola Ronald E
Department of Chemistry and Biochemistry, University of Toledo, Toledo, OH 43606, USA.
Acta Crystallogr F Struct Biol Commun. 2015 Nov;71(Pt 11):1365-71. doi: 10.1107/S2053230X15017495. Epub 2015 Oct 23.
Aspartate semialdehyde dehydrogenase (ASADH) functions at a critical junction in the aspartate-biosynthetic pathway and represents a valid target for antimicrobial drug design. This enzyme catalyzes the NADPH-dependent reductive dephosphorylation of β-aspartyl phosphate to produce the key intermediate aspartate semialdehyde. Production of this intermediate represents the first committed step in the biosynthesis of the essential amino acids methionine, isoleucine and threonine in fungi, and also the amino acid lysine in bacteria. The structure of a new fungal form of ASADH from Cryptococcus neoformans has been determined to 2.6 Å resolution. The overall structure of CnASADH is similar to those of its bacterial orthologs, but with some critical differences both in biological assembly and in secondary-structural features that can potentially be exploited for the development of species-selective drugs.
天冬氨酸半醛脱氢酶（ASADH）在天冬氨酸生物合成途径的一个关键节点发挥作用，是抗菌药物设计的一个有效靶点。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。这种中间体的产生是真菌中必需氨基酸甲硫氨酸、异亮氨酸和苏氨酸生物合成的第一个关键步骤，也是细菌中赖氨酸生物合成的关键步骤。新型隐球菌的一种新的真菌形式的ASADH结构已确定至2.6 Å分辨率。新型隐球菌ASADH（CnASADH）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物种选择性药物。
