肽聚糖是微生物细胞壁的主要组成部分，参与细胞的形态发生、生长与分裂等多种重要的生理过程。在大肠杆菌中，大约40%-50%的肽聚糖在水解之后，其产物都能够被循环再利用重新形成肽聚糖。肽聚糖水解酶LdcA在肽聚糖的循环再利用过程中发挥重要作用。目前，LdcA的底物特异性和作用位点已得到比较详细的研究，但其在分子水平上的催化反应机理及小分子抑制剂对它的抑制机制尚未得到阐述。本项目拟运用X射线晶体学的方法系统的测定LdcA及其与底物、抑制剂复合物的三维结构，通过结构比较、分析和定点突变等实验确定其活性位点及抑制剂结合位点，阐明结构与功能的关系，从而揭示LdcA的催化反应机制和抑制剂对LdcA的抑制机理。此外，肽聚糖水解酶LdcA是一种潜在的抗生素类药物靶点，因此，期望本项目能够为新型抗菌药物的设计提供直接的理论指导。

Peptidoglycan (PG) is an essential component of the bacterial cell wall and takes participate in many physiological processes such as cellular morphogenesis, cell growth and cell division. In growing E. coli cells, PG synthesis is associated with a 40 to 50% turnover per generation of the cell wall PG. LdcA plays a key role in PG turnover and reclying. To date,its cleavage site and the substrate specifity were widely studied.However,the molecular catalytic and inhibitory mechanismes of LdcA are still unknown. The project is aimed to determine the 3D structures of the native protein and the complexes with their substrate and inhibitor using X-ray crystallography and then identify the active site and the inhibitor binding site via structure comparison/analysis and site-directed mutagenesis. Accordingly, the relationships between structure and function were demonstrated, and the molecular and inhibitory mechanisms were revealed. Additionally, because PG hydrolase LdcA may become a potential target of antibiotics, the results got from this project could give useful clues for antimicrobial drug designation.