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Effect of R119G Mutation on Human P5CR1 Dynamic Property and Enzymatic Activity
Joint Authors
Li, Linhua
Ye, Yujia
Sang, Peng
Yin, Yirui
Hu, Wei
Wang, Jing
Zhang, Chao
Li, Deyun
Wan, Wen
Li, Rui
Li, Longjun
Ma, Linling
Xie, Yuehui
Meng, Zhaohui
Source
Issue
Vol. 2017, Issue 2017 (31 Dec. 2017), pp.1-8, 8 p.
Publisher
Hindawi Publishing Corporation
Publication Date
2017-01-18
Country of Publication
Egypt
No. of Pages
8
Main Subjects
Abstract EN
Pyrroline-5-carboxylate reductase (P5CR1) is a universal housekeeping enzyme that catalyzes the reduction of Δ1-pyrroline-5-carboxylate (P5C) to proline with concomitant oxidation of NAD(P)H to NAD(P)+.
The enzymatic cycle between P5C and proline is important for function in amino acid metabolism, apoptosis, and intracellular redox potential balance in mitochondria.
Autosomal recessive cutis laxa (ARCL) results from a mutation in P5CR1 encoded by PYCR1.
Specifically, the R119G mutation is reported to be linked to ARCL although it has not yet been characterized.
We synthesized R119G P5CR1 and compared it to WT P5CR1.
Foldx prediction of WT and R119G mutant P5CR1 protein stability suggests that the R119G mutation could significantly reduce protein stability.
We also performed enzymatic activity assays to determine how the mutation impacts P5CR1 enzymatic function.
The results of these experiments show that mutagenesis of R119 to G decreases P5CR1 catalytic efficiency for 3,4-dehydro-L-proline relative to WT.
Mutagenesis and kinetic studies reveal that the activity of the mutant decreases as temperature increases from 5°C to 37°C, with almost no activity at 37°C, indicating that this mutation impairs P5CR1 function in vivo.
Conversely, WT P5CR1 retains its activity after incubation at 37°C and has essentially no remaining activity at 75°C.
Taken together, our experimental results indicate the R119G mutation could be an involving pathomechanism for ARCL.
American Psychological Association (APA)
Li, Linhua& Ye, Yujia& Sang, Peng& Yin, Yirui& Hu, Wei& Wang, Jing…[et al.]. 2017. Effect of R119G Mutation on Human P5CR1 Dynamic Property and Enzymatic Activity. BioMed Research International،Vol. 2017, no. 2017, pp.1-8.
https://search.emarefa.net/detail/BIM-1136836
Modern Language Association (MLA)
Li, Linhua…[et al.]. Effect of R119G Mutation on Human P5CR1 Dynamic Property and Enzymatic Activity. BioMed Research International No. 2017 (2017), pp.1-8.
https://search.emarefa.net/detail/BIM-1136836
American Medical Association (AMA)
Li, Linhua& Ye, Yujia& Sang, Peng& Yin, Yirui& Hu, Wei& Wang, Jing…[et al.]. Effect of R119G Mutation on Human P5CR1 Dynamic Property and Enzymatic Activity. BioMed Research International. 2017. Vol. 2017, no. 2017, pp.1-8.
https://search.emarefa.net/detail/BIM-1136836
Data Type
Journal Articles
Language
English
Notes
Includes bibliographical references
Record ID
BIM-1136836