More details on GSK-3

Contents

Overview

Glycogen synthase kinase-3 (GSK-3) has recently emerged, in the field of medicinal chemistry, as one of the most attractive therapeutic targets for the development of selective inhibitors as promising new drugs for numerous serious pathologies, including Alzheimer's disease, stroke, bipolar disorders, chronic inflammatory processes, cancer, alopecia and Type II diabetes. The full potential of GSK-3 inhibitors is yet to be realised and the number of drug candidates being developed by both academic centres and pharmaceutical companies has increased exponentially in the last three years. This review discloses recent discoveries on peptides and small molecules targeting GSK-3. Antisense therapy for the modulation of GSK-3 expression is also discussed. Focusing attention on this exciting target could thus reap considerable clinical and economic rewards. source


Protein name:Glycogen synthase kinase-3 alpha

Synonyms: EC 2.7.11.26; GSK-3 alpha

Gene name :Name: GSK3A

From : Homo sapiens (Human) [TaxID: 9606]

Function: Participates in the Wnt signaling pathway. Implicated in the hormonal control of several regulatory proteins including glycogen synthase, MYB and the transcription factor JUN. Phosphorylates JUN at sites proximal to its DNA-binding domain, thereby reducing its affinity for DNA.

Structural details

Atomic composition:

Prediction search done on NetPhos 2.0 server for GSK3

Prediction search done on NetPhos 2.0 server, which produces neural network predictions for serine, threonine and tyrosine phosphorylation sites in eukaryotic proteins.

Predication-gsk3.jpg

DISPHOS (Disorder-Enhanced Phosphorylation Sites Predictor) Results

Predication-gsk3-2.jpg

Amino Acid Sequence

GSK3B_HUMAN consists of 420 amino acids sequemnce.

Gsk-3 sequence.jpg

Ways to inhibit GSK3

Possible ways in the art to inihibit GSK3 is illustrated in following figure:

Ways to inhibit gsk3.jpg

Beta-catenin

Structure

Beta-catenin consists of 781 amino acid residue.

Catenin.jpg

Amino Acid Sequence

1 MATQADLMEL DMAMEPDRKA AVSHWQQQSY LDSGIHSGAT TTAPSLSGKG NPEEEDVDTS
61 QVLYEWEQGF SQSFTQEQVA DIDGQYAMTR AQRVRAAMFP ETLDEGMQIP STQFDAAHPT
121 NVQRLAEPSQ MLKHAVVNLI NYQDDAELAT RAIPELTKLL NDEDQVVVNK AAVMVHQLSK
181 KEASRHAIMR SPQMVSAIVR TMQNTNDVET ARCTAGTLHN LSHHREGLLA IFKSGGIPAL
241 VKMLGSPVDS VLFYAITTLH NLLLHQEGAK MAVRLAGGLQ KMVALLNKTN VKFLAITTDC
301 LQILAYGNQE SKLIILASGG PQALVNIMRT YTYEKLLWTT SRVLKVLSVC SSNKPAIVEA
361 GGMQALGLHL TDPSQRLVQN CLWTLRNLSD AATKQEGMEG LLGTLVQLLG SDDINVVTCA
421 AGILSNLTCN NYKNKMMVCQ VGGIEALVRT VLRAGDREDI TEPAICALRH LTSRHQEAEM
481 AQNAVRLHYG LPVVVKLLHP PSHWPLIKAT VGLIRNLALC PANHAPLREQ GAIPRLVQLL
541 VRAHQDTQRR TSMGGTQQQF VEGVRMEEIV EGCTGALHIL ARDVHNRIVI RGLNTIPLFV
601 QLLYSPIENI QRVAAGVLCE LAQDKEAAEA IEAEGATAPL TELLHSRNEG VATYAAAVLF
661 RMSEDKPQDY KKRLSVELTS SLFRTEPMAW NETADLGLDI GAQGEPLGYR QDDPSYRSFH
721 SGGYGQDALG MDPMMEHEMG GHHPGADYPV DGLPDLGHAQ DLMDGLPPGD SNQLAWFDTD
781 l

Role of beta catenin


In action.jpg