Linked Life Data

12614615

Source:http://linkedlifedata.com/resource/pubmed/id/12614615

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
1
pubmed:dateCreated
2003-3-4
pubmed:databankReference
pubmed:abstractText
To better understand the mechanism of ligand binding and ligand-induced conformational change, the crystal structure of apoenzyme catalytic (C) subunit of adenosine-3',5'-cyclic monophosphate (cAMP)-dependent protein kinase (PKA) was solved. The apoenzyme structure (Apo) provides a snapshot of the enzyme in the first step of the catalytic cycle, and in this unliganded form the PKA C subunit adopts an open conformation. A hydrophobic junction is formed by residues from the small and large lobes that come into close contact. This "greasy" patch may lubricate the shearing motion associated with domain rotation, and the opening and closing of the active-site cleft. Although Apo appears to be quite dynamic, many important residues for MgATP binding and phosphoryl transfer in the active site are preformed. Residues around the adenine ring of ATP and residues involved in phosphoryl transfer from the large lobe are mostly preformed, whereas residues involved in ribose binding and in the Gly-rich loop are not. Prior to ligand binding, Lys72 and the C-terminal tail, two important ATP-binding elements are also disordered. The surface created in the active site is contoured to bind ATP, but not GTP, and appears to be held in place by a stable hydrophobic core, which includes helices C, E, and F, and beta strand 6. This core seems to provide a network for communicating from the active site, where nucleotide binds, to the peripheral peptide-binding F-to-G helix loop, exemplified by Phe239. Two potential lines of communication are the D helix and the F helix. The conserved Trp222-Phe238 network, which lies adjacent to the F-to-G helix loop, suggests that this network would exist in other protein kinases and may be a conserved means of communicating ATP binding from the active site to the distal peptide-binding ledge.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Mar
pubmed:issn
0022-2836
pubmed:author
pubmed:issnType
Print
pubmed:day
14
pubmed:volume
327
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
159-71
pubmed:dateRevised
2010-11-18
pubmed:meshHeading
pubmed-meshheading:12614615-Adenosine, pubmed-meshheading:12614615-Adenosine Triphosphate, pubmed-meshheading:12614615-Amino Acid Sequence, pubmed-meshheading:12614615-Animals, pubmed-meshheading:12614615-Apoenzymes, pubmed-meshheading:12614615-Binding Sites, pubmed-meshheading:12614615-Crystallography, X-Ray, pubmed-meshheading:12614615-Cyclic AMP-Dependent Protein Kinases, pubmed-meshheading:12614615-Hydrophobic and Hydrophilic Interactions, pubmed-meshheading:12614615-Mice, pubmed-meshheading:12614615-Models, Molecular, pubmed-meshheading:12614615-Molecular Sequence Data, pubmed-meshheading:12614615-Protein Conformation, pubmed-meshheading:12614615-Protein Subunits, pubmed-meshheading:12614615-Ribose, pubmed-meshheading:12614615-Static Electricity, pubmed-meshheading:12614615-Substrate Specificity
pubmed:year
2003
pubmed:articleTitle
Dynamic features of cAMP-dependent protein kinase revealed by apoenzyme crystal structure.
pubmed:affiliation
Department of Chemistry and Biochemistry, University of California-San Diego, 9500 Gilman Drive, La Jolla, CA 92093-0654, USA.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S.