Linked Life Data

21241709

Source:http://linkedlifedata.com/resource/pubmed/id/21241709

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
1
pubmed:dateCreated
2011-2-28
pubmed:databankReference
pubmed:abstractText
Protein kinase CK2 (formerly "casein kinase 2") is composed of a central dimer of noncatalytic subunits (CK2?) binding two catalytic subunits. In humans, there are two isoforms of the catalytic subunit (and an additional splicing variant), one of which (CK2?) is well characterized. To supplement the limited biochemical knowledge about the second paralog (CK2?'), we developed a well-soluble catalytically active full-length mutant of human CK2?', characterized it by Michaelis-Menten kinetics and isothermal titration calorimetry, and determined its crystal structure to a resolution of 2 Å. The affinity of CK2?' for CK2? is about 12 times lower than that of CK2? and is less driven by enthalpy. This result fits the observation that the ?4/?5 loop, a key element of the CK2?/CK2? interface, adopts an open conformation in CK2?', while in CK2?, it opens only after assembly with CK2?. The open ?4/?5 loop in CK2?' is stabilized by two elements that are absent in CK2?: (1) the extension of the N-terminal ?-sheet by an additional ?-strand, and (2) the filling of a conserved hydrophobic cavity between the ?4/?5 loop and helix ?C by a tryptophan residue. Moreover, the interdomain hinge region of CK2?' adopts a fully functional conformation, while unbound CK2? is often found with a nonproductive hinge conformation that is overcome only by CK2? binding. Taken together, CK2?' exhibits a significantly lower affinity for CK2? than CK2?; moreover, in functionally critical regions, it is less dependent on CK2? to obtain a fully functional conformation.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Mar
pubmed:issn
1089-8638
pubmed:author
pubmed:copyrightInfo
Copyright © 2011 Elsevier Ltd. All rights reserved.
pubmed:issnType
Electronic
pubmed:day
18
pubmed:volume
407
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
1-12
pubmed:meshHeading
pubmed:year
2011
pubmed:articleTitle
Structure of the human protein kinase CK2 catalytic subunit CK2?' and interaction thermodynamics with the regulatory subunit CK2?.
pubmed:affiliation
Department für Chemie, Institut für Biochemie, Universität zu Köln, Zülpicher Straße 47, D-50674 Köln, Germany.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't