مورد إلكتروني
Polymorphic Variants of Human Protein l-Isoaspartyl Methyltransferase Affect Catalytic Activity, Aggregation, and Thermal Stability: IMPLICATIONS FOR THE ETIOLOGY OF NEUROLOGICAL DISORDERS AND COGNITIVE AGING.
| العنوان: | Polymorphic Variants of Human Protein l-Isoaspartyl Methyltransferase Affect Catalytic Activity, Aggregation, and Thermal Stability: IMPLICATIONS FOR THE ETIOLOGY OF NEUROLOGICAL DISORDERS AND COGNITIVE AGING. |
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| المؤلفون: | Juang, Charity |
| المصدر: | The Journal of biological chemistry; vol 292, iss 9, 3656-3665; 0021-9258 |
| بيانات النشر: | eScholarship, University of California 2017-03-01 |
| تفاصيل مُضافة: | Juang, Charity Chen, Baihe Bru, Jean-Louis Nguyen, Katherine Huynh, Eric Momen, Mahsa Kim, Jeungjin Aswad, Dana W |
| نوع الوثيقة: | Electronic Resource |
| مستخلص: | Protein l-isoaspartyl methyltransferase (PIMT/PCMT1), a product of the human pcmt1 gene, catalyzes repair of abnormal l-isoaspartyl linkages in age-damaged proteins. Pcmt1 knock-out mice exhibit a profound neuropathology and die 30-60 days postnatal from an epileptic seizure. Here we express 15 reported variants of human PIMT and characterize them with regard to their enzymatic activity, thermal stability, and propensity to aggregation. One mutation, R36C, renders PIMT completely inactive, whereas two others, A7P and I58V, exhibit activity that is 80-100% higher than wild type. G175R is highly prone to aggregation and has greatly reduced activity. R17S and R17H show markedly enhanced sensitivity to thermal denaturation. Based on previous studies of moderate PIMT variation in humans and mice, we predict that heterozygosity for R36C, G175R, R17S, and R17H will prove detrimental to cognitive function and successful aging, whereas homozygosity (if it ever occurs) will lead to severe neurological problems in the young. |
| مصطلحات الفهرس: | Brain, Humans, Nervous System Diseases, Epilepsy, Protein D-Aspartate-L-Isoaspartate Methyltransferase, Isoaspartic Acid, Fluorometry, Sequence Analysis, DNA, Computational Biology, Temperature, Genotype, Mutation, Polymorphism, Single Nucleotide, Alleles, Catalysis, Cognitive Aging, S-adenosylmethionine, epilepsy, genetic polymorphism, neurological disease, protein aggregation, protein methylation, protein stability, recombinant protein expression, Genetics, Aging, Brain Disorders, Biotechnology, 2.1 Biological and endogenous factors, Aetiology, Neurological, Chemical Sciences, Biological Sciences, Medical and Health Sciences, Biochemistry & Molecular Biology, article |
| URL: | |
| الإتاحة: | Open access content. Open access content public |
| ملاحظة: | application/pdf The Journal of biological chemistry vol 292, iss 9, 3656-3665 0021-9258 |
| أرقام أخرى: | CDLER oai:escholarship.org:ark:/13030/qt46n617f2 qt46n617f2 https://escholarship.org/uc/item/46n617f2Test https://escholarship.orgTest/ 1391614915 |
| المصدر المساهم: | UC MASS DIGITIZATION From OAIster®, provided by the OCLC Cooperative. |
| رقم الانضمام: | edsoai.on1391614915 |
| قاعدة البيانات: | OAIster |
| الوصف غير متاح. |