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 knockout 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, while 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, while homozygosity (if it ever occurs) will lead to severe neurological problems in the young.
from #AlexandrosSfakianakis via Alexandros G.Sfakianakis on Inoreader http://ift.tt/2joFNTV
via IFTTT
Εγγραφή σε:
Σχόλια ανάρτησης (Atom)
Δημοφιλείς αναρτήσεις
-
Publication date: March 2017 Source: Free Radical Biology and Medicine, Volume 104 from #AlexandrosSfakianakis via Alexandros G.Sfak...
-
Publication date: July 2017 Source: European Journal of Cancer, Volume 79 Author(s): Simon Pernot, Cecile Badoual, Magali Terme, Florence...
-
Abstract Autosomal dominant polycystic kidney disease (ADPKD) is a common monogenetic disorder that is caused by mutations in the genes PK...
-
Inflammation is an important component of diabetic retinal damage. We previously reported that a novel β-adrenergic receptor agonist, Compou...
-
An ambitious plan to save a melting glacier in the Swiss Alps with showers of artificial snow will be tested this summer from #AlexandrosS...
-
by Yiquan Wu, Adrian Prager, Simone Boos, Moritz Resch, Ilija Brizic, Michael Mach, Sabrina Wildner, Laura Scrivano, Barbara Adler Herpesv...
-
Abstract The aims of this study were to (1) determine if older people at their fast walking speed (FWS) are able to reach the speed require...
-
Clinical characteristics and treatment of thyroid cancer in children and adolescents: a retrospective analysis of 83 patients. J Zheji...
-
Background: Hidradenitis suppurativa (HS) is a long-term skin disorder associated with high levels of psychological distress and significan...
Δεν υπάρχουν σχόλια:
Δημοσίευση σχολίου