Molecules, Vol. 29, Pages 2029: Exploring the Key Amino Acid Residues Surrounding the Active Center of Lactate Dehydrogenase A for the Development of Ideal Inhibitors

Molecules, Vol. 29, Pages 2029: Exploring the Key Amino Acid Residues Surrounding the Active Center of Lactate Dehydrogenase A for the Development of Ideal Inhibitors
Molecules doi: 10.3390/molecules29092029
Authors:
Jie Chen
Chen Chen
Zhengfu Zhang
Fancai Zeng
Shujun Zhang

Lactate dehydrogenase A (LDHA) primarily catalyzes the conversion between lactic acid and pyruvate, serving as a key enzyme in the aerobic glycolysis pathway of sugar in tumor cells. LDHA plays a crucial role in the occurrence, development, progression, invasion, metastasis, angiogenesis, and immune escape of tumors. Consequently, LDHA not only serves as a biomarker for tumor diagnosis and prognosis but also represents an ideal target for tumor therapy. Although LDHA inhibitors show great therapeutic potential, their development has proven to be challenging. In the development of LDHA inhibitors, the key active sites of LDHA are emphasized. Nevertheless, there is a relative lack of research on the amino acid residues around the active center of LDHA. Therefore, in this study, we investigated the amino acid residues around the active center of LDHA. Through structure comparison analysis, five key amino acid residues (Ala30, Met41, Lys131, Gln233, and Ala259) were identified. Subsequently, the effects of these five residues on the enzymatic properties of LDHA were investigated using site-directed mutagenesis. The results revealed that the catalytic activities of the five mutants varied to dif...

Source: Molecules - April 28, 2024 Category: Chemistry Authors: Jie Chen Chen Chen Zhengfu Zhang Fancai Zeng Shujun Zhang Tags: Article Source Type: research