氨氯地平与溶菌酶的络合及其对溶菌酶晶体生长的影响的研究。,Spectrochimica Acta Part A: Molecular and Biomolecular Spectroscopy

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氨氯地平与溶菌酶的络合及其对溶菌酶晶体生长的影响的研究。
Spectrochimica Acta Part A: Molecular and Biomolecular Spectroscopy ( IF 4.3 ) Pub Date : 2019-10-07 , DOI: 10.1016/j.saa.2019.117623
Satish Pawar ₁ , Kusaji Raul ₁ , Divya Ottoor ₁

Affiliation

溶菌酶（LYZ）是一种模型蛋白质，由于其体积小且具有快速的结晶行为，因此经常用于研究与药物的相互作用并了解蛋白质的结晶过程。如果可获得合适的药物-溶菌酶晶体，则与药物相互作用和与蛋白质的络合有关的研究将大大受益。这可以进一步帮助理解成核，生长和药物-溶菌酶复合物形成的机理。在本研究中，已经监测了氨氯地平（AMLD）与LYZ的络合以及对溶菌酶结晶的影响。与AMLD相互作用后，已采用了不同的光谱方法来监测络合的性质，结合模式和螺旋的变化。吸光度和荧光光谱测量表明，LYZ和AMLD之间存在基态复合物的可能性。此外，依赖温度的荧光研究表明结合常数随温度的升高而增加，这表明由于疏水相互作用，参与复合物形成的静态猝灭机理。CD，FTIR，DLS和DSC技术证实了蛋白质三级结构发生变化的可能性。应用分子对接技术研究了LYZ氨基酸残基与AMLD的相互作用。发现复合物的形成是自发的，并且获得的ΔG值（-21。76 kJ / mol）与温度依赖性荧光研究（-24.91 kJ / mol）非常匹配。用不同浓度的AMLD进行LYZ的结晶，以清楚地了解其对工艺的干扰。AMLD-LYZ配合物结晶所需的时间和观察到的晶体结构表明，AMLD通过改变成核性质和晶体生长速率影响溶菌酶的结晶过程。

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Investigation of complexation of amlodipine with lysozyme and its effect on lysozyme crystal growth.

Lysozyme (LYZ) is a model protein frequently employed to study interaction with drugs and to understand the crystallization process of protein due to its small size and rapid crystallization behavior. Studies related to drug interaction and complexation with proteins will be significantly benefited if a suitable drug-lysozyme crystal is available. This can further aid in the understanding of the mechanism of nucleation, growth and the formation of drug-lysozyme complex. In the present study, amlodipine (AMLD) complexation with LYZ has been monitored, along with its effect on lysozyme crystallization. Different spectroscopic methods have been employed to monitor the nature of complexation, binding mode and changes in helix after interaction with AMLD. The absorbance and fluorescence spectroscopic measurement indicated the probability of a ground state complex between LYZ and AMLD. Further, the temperature dependent fluorescence studies showed an increase in binding constant with temperature, suggesting the static quenching mechanism involved in complex formation due to hydrophobic interactions. CD, FTIR, DLS and DSC techniques confirm the probability of changes in the tertiary structure of protein. Molecular docking was applied to investigate the interaction of amino acid residues of LYZ with AMLD. It was found that the complex formation is spontaneous and the ΔG value obtained (-21. 76 kJ/mol) very well matched with temperature dependent fluorescence study (-24.91 kJ/mol). Crystallization of LYZ was performed with different concentration ranges of AMLD to get a clear picture of its interference on the process. The time required for crystallization of AMLD-LYZ complex and the observed structure of crystal indicates that AMLD influences lysozyme crystallization process by changing the nature of nucleation and rate of crystal growth.

更新日期：2019-10-07

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