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Effect of SNPs on Creatine Kinase Structure and Function: Identifying Potential Molecular Mechanisms for Possible Creatine Kinase Deficiency Diseases

Single-nucleotide polymorphisms (SNPs) are common genetic material changes that often occur naturally. SNPs can cause amino acid replacements that may lead to severe diseases, such as the well-known sickle-cell anemia. We constructed eight SNP mutants of human brain-type creatine kinase (CKB) based...

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Autores principales: Li, Chang, Zhang, Qian, Hu, Wei-Jiang, Mu, Hang, Lin, Zong, Ma, Long, Park, Yong-Doo, Zhou, Hai-Meng
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2012
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3457962/
https://www.ncbi.nlm.nih.gov/pubmed/23049898
http://dx.doi.org/10.1371/journal.pone.0045949
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author Li, Chang
Zhang, Qian
Hu, Wei-Jiang
Mu, Hang
Lin, Zong
Ma, Long
Park, Yong-Doo
Zhou, Hai-Meng
author_facet Li, Chang
Zhang, Qian
Hu, Wei-Jiang
Mu, Hang
Lin, Zong
Ma, Long
Park, Yong-Doo
Zhou, Hai-Meng
author_sort Li, Chang
collection PubMed
description Single-nucleotide polymorphisms (SNPs) are common genetic material changes that often occur naturally. SNPs can cause amino acid replacements that may lead to severe diseases, such as the well-known sickle-cell anemia. We constructed eight SNP mutants of human brain-type creatine kinase (CKB) based on bioinformatics predictions. The biochemical and biophysical characteristics of these SNP mutants were determined and compared to those of the wild-type creatine kinase to explore the potential molecular mechanisms of possible creatine kinase SNP-induced diseases. While the reactivation of six SNP mutants after heat shock dropped more than 45%, only three of them showed notable increases in ANS fluorescence intensity and decreases in catalytic efficiency. Among them, H26Y and P36T bind substrates as well as the wild-type form does, but the melting temperatures (T(m)) dropped below body temperature, while the T59I mutant exhibited decreased catalytic activity that was most likely due to the much reduced binding affinity of this mutant for substrates. These findings indicate that SNPs such as H26Y, P36T and T59I have the potential to induce genetic diseases by different mechanisms.
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spelling pubmed-34579622012-10-03 Effect of SNPs on Creatine Kinase Structure and Function: Identifying Potential Molecular Mechanisms for Possible Creatine Kinase Deficiency Diseases Li, Chang Zhang, Qian Hu, Wei-Jiang Mu, Hang Lin, Zong Ma, Long Park, Yong-Doo Zhou, Hai-Meng PLoS One Research Article Single-nucleotide polymorphisms (SNPs) are common genetic material changes that often occur naturally. SNPs can cause amino acid replacements that may lead to severe diseases, such as the well-known sickle-cell anemia. We constructed eight SNP mutants of human brain-type creatine kinase (CKB) based on bioinformatics predictions. The biochemical and biophysical characteristics of these SNP mutants were determined and compared to those of the wild-type creatine kinase to explore the potential molecular mechanisms of possible creatine kinase SNP-induced diseases. While the reactivation of six SNP mutants after heat shock dropped more than 45%, only three of them showed notable increases in ANS fluorescence intensity and decreases in catalytic efficiency. Among them, H26Y and P36T bind substrates as well as the wild-type form does, but the melting temperatures (T(m)) dropped below body temperature, while the T59I mutant exhibited decreased catalytic activity that was most likely due to the much reduced binding affinity of this mutant for substrates. These findings indicate that SNPs such as H26Y, P36T and T59I have the potential to induce genetic diseases by different mechanisms. Public Library of Science 2012-09-25 /pmc/articles/PMC3457962/ /pubmed/23049898 http://dx.doi.org/10.1371/journal.pone.0045949 Text en © 2012 Li et al http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited.
spellingShingle Research Article
Li, Chang
Zhang, Qian
Hu, Wei-Jiang
Mu, Hang
Lin, Zong
Ma, Long
Park, Yong-Doo
Zhou, Hai-Meng
Effect of SNPs on Creatine Kinase Structure and Function: Identifying Potential Molecular Mechanisms for Possible Creatine Kinase Deficiency Diseases
title Effect of SNPs on Creatine Kinase Structure and Function: Identifying Potential Molecular Mechanisms for Possible Creatine Kinase Deficiency Diseases
title_full Effect of SNPs on Creatine Kinase Structure and Function: Identifying Potential Molecular Mechanisms for Possible Creatine Kinase Deficiency Diseases
title_fullStr Effect of SNPs on Creatine Kinase Structure and Function: Identifying Potential Molecular Mechanisms for Possible Creatine Kinase Deficiency Diseases
title_full_unstemmed Effect of SNPs on Creatine Kinase Structure and Function: Identifying Potential Molecular Mechanisms for Possible Creatine Kinase Deficiency Diseases
title_short Effect of SNPs on Creatine Kinase Structure and Function: Identifying Potential Molecular Mechanisms for Possible Creatine Kinase Deficiency Diseases
title_sort effect of snps on creatine kinase structure and function: identifying potential molecular mechanisms for possible creatine kinase deficiency diseases
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3457962/
https://www.ncbi.nlm.nih.gov/pubmed/23049898
http://dx.doi.org/10.1371/journal.pone.0045949
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