Precise control of the cell cycle allows for timely repair of genetic material prior to replication. One factor intimately involved in this process is checkpoint kinase 1 (Chk1), a DNA damage repair inducing Ser/Thr protein kinase that contains an N-terminal kinase domain and a C-terminal regulatory region consisting of a ∼100-residue linker followed by a putative kinase-associated 1 (KA1) domain. We report the crystal structure of the human Chk1 KA1 domain, demonstrating striking structural homology with other sequentially diverse KA1 domains. Separately purified Chk1 kinase and KA1 domains are intimately associated in solution, which results in inhibition of Chk1 kinase activity. Using truncation mutants and site-directed mutagenesis, we define the inhibitory face of the KA1 domain as a series of basic residues residing on two conserved regions of the primary structure. These findings point to KA1-mediated intramolecular autoinhibition as a key regulatory mechanism of human Chk1, and provide new therapeutic possibilities with which to attack this validated oncology target with small molecules.
from #AlexandrosSfakianakis via Alexandros G.Sfakianakis on Inoreader http://ift.tt/2jxT3d9
via IFTTT
Εγγραφή σε:
Σχόλια ανάρτησης (Atom)
Δημοφιλείς αναρτήσεις
-
Publication date: Available online 4 January 2018 Source: European Journal of Radiology Author(s): Peiyao Zhang, Jing Wang, Qin Xu, Zhen...
-
BACKGROUND AND PURPOSE: Lesion load is a common biomarker in multiple sclerosis, yet it has historically shown modest association with cl...
-
Does CBD Oil Lower Blood Pressure? This article was originally published at SundayScaries." Madeline Taylor POSTED ON January 13, 20...
-
Despite widespread journal endorsement of reporting guidelines, the poor reproducibility of preclinical research is increasingly under debat...
-
The benefit of the breastfeeding has been well-established. In comparison to partial breast feeding, exclusive breastfeeding has even more b...
-
A report of the Cold Spring Harbor Laboratory/Wellcome Trust Meeting on Engineering Principles in Biology, Cambridge, UK, 14-16 October 2009...
-
Abstract We report here a microscopic tight-binding theoretical study of the dynamic dielectric response of graphene-on-polarizable substr...
-
Volumetry measurement of lung nodules is gaining clinical acceptance but still... Read more on AuntMinnieEurope.com Related Reading: Ul...
-
Background Hyperthyroidism is associated with increased thrombotic risk. As contact system activation through formation of neutrophil extrac...
Δεν υπάρχουν σχόλια:
Δημοσίευση σχολίου