Document Detail


Thymoquinone Blocks pSer/pThr Recognition by Plk1 Polo-Box Domain as a Phosphate Mimic.
MedLine Citation:
PMID:  23135290     Owner:  NLM     Status:  Publisher    
Abstract/OtherAbstract:
Phosphorylation-dependent protein-protein interaction has rarely been targeted in medicinal chemistry. Thymoquinone, a naturally occurring antitumor agent, disrupts pre-phosphorylated substrate recognition by the polo-box domain of polo-like kinase 1, a key mitotic regulator responsible for various carcinogenesis when over-expressed. Here, crystallographic studies reveal that the phosphoserine/phosphothreonine recognition site of the polo-box domain is the binding pocket for thymoquinone and its analogue poloxime. Both small molecules displace phosphopeptides bound with the polo-box domain in a slow but non-covalent binding mode. A conserved water bridge and a cation-π interaction were found as their competition strategy against the phosphate group. This mechanism shed lights on small-molecule intervention of phospho-recognition by the polo-box domain of polo-like kinase 1 and other phospho-binding proteins in general.
Authors:
Zhou Yin; Yunlong Song; Peter H Rehse
Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2012-11-7
Journal Detail:
Title:  ACS chemical biology     Volume:  -     ISSN:  1554-8937     ISO Abbreviation:  ACS Chem. Biol.     Publication Date:  2012 Nov 
Date Detail:
Created Date:  2012-11-8     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  101282906     Medline TA:  ACS Chem Biol     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
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