University of Madras, CAS in Crystallography and Biophysics , Chennai , India.
J Enzyme Inhib Med Chem. 2013 Oct;28(5):1054-60. doi: 10.3109/14756366.2012.710849. Epub 2012 Sep 7.
The aspartic protease inhibitory efficiency of rBm-33, an aspin from a filarial parasite Brugia malayi was investigated. rBm-33 was found to be thermostable up to 90°C and it forms a stable 'enzyme-product' complex with human pepsin. Aspartic protease inhibitory activity was investigated using UV spectroscopy and isothermal titration calorimetry. Our results suggest that rBm-33 inhibits the activity of important human aspartic proteases that were examined with binding constants (Kb) values between 10.23 × 10(3) and 6.52 × 10(3) M(-1). The binding reactions were enthalpy driven with ΔHb values between -50.99 and -46.07 kJ mol(-1). From kinetic studies, pepsin inhibition by rBm-33 was found to be linear competitive with an inhibition constant (Ki) of 2.5 (±0.8) nM. Because of the inhibitory efficacy of Bm-33 against important human aspartic proteases which play a vital role in immune-regulation along with other functions, Bm-33 can be projected as a drug target for the filariasis.
研究了一种来自丝虫寄生虫布鲁氏线虫的 aspin rBm-33 对天冬氨酸蛋白酶的抑制效率。发现 rBm-33 可在高达 90°C 的温度下稳定，并与人胃蛋白酶形成稳定的“酶-产物”复合物。使用紫外光谱法和等温热力学滴定法研究了天冬氨酸蛋白酶抑制活性。我们的结果表明，rBm-33 抑制了重要的人类天冬氨酸蛋白酶的活性，用结合常数（Kb）值在 10.23×10(3) 和 6.52×10(3) M(-1)之间进行了检查。结合反应是焓驱动的，ΔHb 值在-50.99 和-46.07 kJ mol(-1)之间。从动力学研究中可以发现，rBm-33 对胃蛋白酶的抑制作用呈线性竞争抑制，抑制常数（Ki）为 2.5（±0.8）nM。由于 Bm-33 对在免疫调节以及其他功能中起着重要作用的重要人类天冬氨酸蛋白酶具有抑制作用，因此 Bm-33 可以作为丝虫病的药物靶标。
