The haloacid dehalogenase superfamily implicated in bacterial pathogenesis comprises different enzymes having roles in many metabolic pathways. Staphylococcus lugdunensis, a Gram-positive bacterium, is an opportunistic human pathogen causing infections in the central nervous system, urinary tract, bones, peritoneum, systemic conditions and cutaneous infection. The haloacid dehalogenase superfamily proteins play a significant role in the pathogenicity of certain bacteria, facilitating invasion, survival, and proliferation within host cells. The genome of S. lugdunensis encodes more than ten proteins belonging to this superfamily. However, none of them have been characterized. The present work reports the characterization of one of the haloacid dehalogenase superfamily proteins (SLHAD1) from Staphylococcus lugdunensis. The functional analysis revealed that SLHAD1 is a metal-dependent acid phosphatase, which catalyzes the dephosphorylation of phosphorylated metabolites of cellular pathways, including glycolysis, gluconeogenesis, nucleotides, and thiamine metabolism. Based on the substrate specificity and genomic analysis, the physiological function of SLHAD1 in thiamine metabolism has been tentatively assigned. The crystal structure of SLHAD1, lacking 49 residues at the C-terminal, was determined at 1.7 Å resolution with a homodimer in the asymmetric unit. It was observed that SLHAD1 exhibited time-dependent cleavage at a specific point, occurring through a self-initiated process. A combination of bioinformatics, biochemical, biophysical, and structural studies explored unique features of SLHAD1. Overall, the study revealed a detailed characterization of a critical enzyme of the human pathogen Staphylococcus lugdunensis, associated with several life-threatening infections.

与细菌发病机制有关的卤酸脱卤酶超家族包含在许多代谢途径中发挥作用的不同酶。路邓葡萄球菌是一种革兰氏阳性细菌，是一种机会性人类病原体，可引起中枢神经系统、泌尿道、骨骼、腹膜、全身性疾病和皮肤感染。卤酸脱卤酶超家族蛋白在某些细菌的致病性中发挥重要作用，促进宿主细胞内的侵袭、存活和增殖。路邓沙门氏菌的基因组编码属于该超家族的十多种蛋白质。然而，它们都没有被表征。目前的工作报告了来自路邓葡萄球菌的一种卤代酸脱卤酶超家族蛋白 (SLHAD1) 的特征。功能分析表明，SLHAD1是一种金属依赖性酸性磷酸酶，催化细胞途径磷酸化代谢物的去磷酸化，包括糖酵解、糖异生、核苷酸和硫胺素代谢。基于底物特异性和基因组分析，初步确定了SLHAD1在硫胺素代谢中的生理功能。 SLHAD1 的晶体结构在C端缺少 49 个残基，通过不对称单元中的同型二聚体以 1.7 Å 分辨率测定。据观察，SLHAD1 在特定点表现出时间依赖性裂解，通过自启动过程发生。 生物信息学、生物化学、生物物理和结构研究相结合，探索了 SLHAD1 的独特特征。总体而言，该研究揭示了人类病原体路邓葡萄球菌的一种关键酶的详细特征，该酶与几种危及生命的感染有关。