1unh

From Proteopedia

Revision as of 12:34, 20 March 2008 by OCA (Talk | contribs)
Jump to: navigation, search
Image:1unh.gif


PDB ID 1unh

Drag the structure with the mouse to rotate
, resolution 2.35Å
Sites:
Ligands:
Coordinates: save as pdb, mmCIF, xml



STRUCTURAL MECHANISM FOR THE INHIBITION OF CDK5-P25 BY ROSCOVITINE, ALOISINE AND INDIRUBIN.


Contents

Overview

The cyclin-dependent kinases (CDK) CDK1, CDK2, CDK4, and CDK6 are serine/threonine protein kinases targeted in cancer therapy due to their role in cell cycle progression. The postmitotic CDK5 is involved in biological pathways important for neuronal migration and differentiation. CDK5 represents an attractive pharmacological target as its deregulation is implicated in various neurodegenerative diseases such as Alzheimer's, Parkinson's, and Niemann-Pick type C diseases, ischemia, and amyotrophic lateral sclerosis. We have generated an improved crystal form of CDK5 in complex with p25, a segment of the p35 neuronal activator. The crystals were used to solve the structure of CDK5/p25 with (R)-roscovitine and aloisine at a resolution of 2.2 and 2.3 A, respectively. The structure of CDK5/p25/roscovitine provides a rationale for the preference of CDK5 for the R over the S stereoisomer. Furthermore, roscovitine stabilized an unusual collapsed conformation of the glycine-rich loop, an important site of CDK regulation, and we report an investigation of the effects of glycine-rich loop phosphorylation on roscovitine binding. The CDK5/p25 crystals represent a valuable new tool for the identification and optimization of selective CDK inhibitors.

Disease

Known diseases associated with this structure: Microcephaly, primary autosomal recessive, 3 OMIM:[608201]

About this Structure

1UNH is a Protein complex structure of sequences from Homo sapiens. Full crystallographic information is available from OCA.

Reference

Mechanism of CDK5/p25 binding by CDK inhibitors., Mapelli M, Massimiliano L, Crovace C, Seeliger MA, Tsai LH, Meijer L, Musacchio A, J Med Chem. 2005 Feb 10;48(3):671-9. PMID:15689152

Page seeded by OCA on Thu Mar 20 14:34:21 2008

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/1unh"
Personal tools