Effect of the R119G mutation on human P5CR structure and its interactions with NAD: Insights derived from molecular dynamics simulation and free energy analysis.
Effect of the R119G mutation on human P5CR structure and its interactions with NAD: Insights derived from molecular dynamics simulation and free energy analysis.
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DOI：
10.1016/j.compbiolchem.2016.12.015
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发表时间：
2016
期刊：
影响因子：
--
通讯作者：
Meng Zhaohui
中科院分区：
文献类型：
--
作者：
Sang Peng;Xie Yuehui;Li Linghua;Ye Yujia;Hu Wei;Wang Jing;Wan Wen;Li Rui;Li Longjun;Ma Linling;Li Zhi;Liu Shuqun;Meng Zhaohui
Pyrroline-5-carboxylate reductase (P5CR), an enzyme with conserved housekeeping.roles, is involved in the etiology of cutis laxa. While previous work has shown.that the R119G point mutation in the P5CR protein is involved, the structural.mechanism behind the pathology remains to be elucidated. In order to probe the.role of the R119G mutation in cutis laxa, we performed molecular dynamics (MD).simulations, essential dynamics (ED) analysis, and Molecular mechanics.Poisson-Boltzmann surface area (MM-PBSA) binding free energy calculations on wild.type (WT) and mutant P5CR-NAD complex. These MD simulations and ED analyses.suggest that the R119G mutation decreases the flexibility of P5CR, specifically.in the substrate binding pocket, which could decrease the kinetics of the.cofactor entrance and egress. Furthermore, the MM-PBSA calculations suggest the.R119G mutant has a lower cofactor binding affinity for NAD than WT. Our study.provides insight into the possible role of the R119G mutation during interactions.between P5CR and NAD, thus bettering our understanding of how the mutation.promotes cutis laxa.
