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Free energy landscapes of prototropic tautomerism in pyridoxal 5′-phosphate schiff bases at the active site of an enzyme in aqueous medium
Journal of Computational Chemistry ( IF 3 ) Pub Date : 2018-05-14 , DOI: 10.1002/jcc.25338
Kumari Soniya 1 , Amalendu Chandra 1
Affiliation  

We have performed hybrid quantum‐classical metadynamics simulations and quantum chemical calculations to investigate the free energy landscapes of intramolecular proton transfer and associated tautomeric equilibrium in pyridoxal 5 ′ ‐phosphate (PLP) Schiff Bases, namely the internal and external aldimines, at the active site of serine hydroxymethyltransferase (SHMT) enzyme in aqueous medium. It is important to determine the relative stability of the two tautomers (ketoenamine and enolimine) of the PLP aldimines to study the catalytic activity of the concerned enzyme. Both the internal PLP aldimine (PLP‐LYS) and the external PLP aldimine (PLP‐SER) of SHMT are found to have a higher stability for the ketoenamine tautomer over the enolimine form. The higher stability of the ketoenamine tautomer can be attributed to the more number of favorable interactions of the ketoenamine form with its surroundings at the active site of the enzyme. The ketoenamine is found to be stabilized by about 2.5 kcal/mol in the PLP‐LYS internal aldimine, while this stabilization is about 6.7 kcal/mol for the PLP‐SER external aldimine at the active site of the enzyme compared to the corresponding enolimine forms. The interactions faced by the PLP aldimines at the active site pocket determine the relative dominance of the tautomers and could possibly alter the tautomeric shift in different PLP dependent enzymes. © 2018 Wiley Periodicals, Inc.

中文翻译:

水介质中酶活性位点的吡哆醛 5'-磷酸希夫碱中质子互变异构的自由能图

我们进行了混合量子-经典元动力学模拟和量子化学计算,以研究分子内质子转移和相关互变异构平衡在活性位点的 5 '-磷酸吡哆醛(PLP)席夫碱(即内部和外部醛亚胺)中的自由能景观丝氨酸羟甲基转移酶 (SHMT) 在水性介质中的测定。确定 PLP 醛亚胺的两个互变异构体(酮烯胺和烯醇亚胺)的相对稳定性对研究相关酶的催化活性很重要。发现 SHMT 的内部 PLP 醛亚胺 (PLP-LYS) 和外部 PLP 醛亚胺 (PLP-SER) 对酮烯胺互变异构体的稳定性高于烯胺形式。酮烯胺互变异构体的更高稳定性可归因于酮烯胺形式与其在酶活性位点的周围环境的更多有利相互作用。发现酮烯胺在 PLP-LYS 内部醛亚胺中的稳定性约为 2.5 kcal/mol,而与相应的烯胺形式相比,酶活性部位的 PLP-SER 外部醛亚胺的稳定性约为 6.7 kcal/mol . PLP 醛亚胺在活性位点口袋处所面临的相互作用决定了互变异构体的相对优势,并且可能会改变不同 PLP 依赖性酶的互变异构转变。© 2018 Wiley Periodicals, Inc. 在 PLP-LYS 内部醛亚胺中为 5 kcal/mol,而在酶活性位点的 PLP-SER 外部醛亚胺与相应的烯亚胺形式相比,这种稳定性约为 6.7 kcal/mol。PLP 醛亚胺在活性位点口袋处所面临的相互作用决定了互变异构体的相对优势,并且可能会改变不同 PLP 依赖性酶的互变异构转变。© 2018 Wiley Periodicals, Inc. 在 PLP-LYS 内部醛亚胺中为 5 kcal/mol,而与相应的烯胺形式相比,PLP-SER 外部醛亚胺在酶活性位点的稳定性约为 6.7 kcal/mol。PLP 醛亚胺在活性位点口袋处所面临的相互作用决定了互变异构体的相对优势,并且可能会改变不同 PLP 依赖性酶的互变异构转变。© 2018 Wiley Periodicals, Inc.
更新日期:2018-05-14
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