NSF Young Investigator

本项目研究酶的结构和机制，特别是那些参与四吡咯生物合成的酶。这一途径对了解血红素、叶绿素、胆色素和胆色素的代谢具有重要意义。5-氨基乙酰丙酸合成酶（5-Aminolevulinate synthase， ALAS）是四吡咯生物合成的第一个酶，也是肝脏血红素生物合成途径的限速酶。ALAS是一种线粒体基质酶，绝对需要5-磷酸吡哆醛（pyridoxal 5-phosphate， PLP）作为辅助因子才能成为一种活性酶。它在细胞质中作为一个更大的前体蛋白合成，并输入线粒体，在那里它被加工成成熟的ALAS蛋白。这些研究旨在阐明ALAS的结构和功能与ALAS前体形式的结构（即折叠状态）与其进入线粒体的关系。从这项研究中获得的知识对于理解血红素生物合成所涉及的酶的结构、机制和调控是必要的和基础的。//

This project examines enzyme structure and mechanism, in particular those involved in the biosynthesis of tetrapyrroles. This pathway is of fundamental importance to the understanding of the metabolism of hemes, chlorophylls, corrins and bile pigments. 5-Aminolevulinate synthase (ALAS) is the first enzyme involved in the biosynthesis of tetrapyrroles, and the rate-limiting enzyme of the heme biosynthetic pathway in the liver. ALAS is a mitochondrial matrix enzyme and has an absolute requirement for pyridoxal 5-phosphate (PLP) as a cofactor, to become an active enzyme. It is synthesized in the cytosol as a larger precursor protein and imported into the mitochondria, where it is processed to yield the mature ALAS protein. The studies are designed to elucidate the relationship of the structure and function of ALAS and the structure (i.e., the folding state) of ALAS precursor form to its import into the mitochondria. %%% The knowledge obtained from this study is both necessary and fundamental to achieve an understanding of the structure, mechanism, and regulation of the enzymes involved in heme biosynthesis.//