NSF Young Investigator

该项目研究酶的结构和机制， 特别是参与四吡咯生物合成的那些。 这条道路对于理解 血红素、叶绿素、咕啉和胆汁的代谢 颜料. 5-氨基乙酰丙酸合成酶（ALAS）是第一个 参与四吡咯生物合成的酶， 血红素生物合成途径的限速酶 肝脏 ALAS是一种线粒体基质酶， 吡哆醛5-磷酸（PLP）作为 辅因子，成为一种活性酶。 它是在 胞质溶胶作为一个更大的前体蛋白，并输入到 线粒体，在那里它被加工以产生成熟的ALAS 蛋白 这些研究旨在阐明 ALAS的结构与功能的关系 结构（即，折叠状态）， 将其导入线粒体。 %%% 从这项研究中获得的知识是必要的， 理解结构的基础， 机制和调控的酶参与血红素 生物合成。//

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.//