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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
17
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pubmed:dateCreated |
2009-9-1
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pubmed:abstractText |
The conformational flexibility exhibited by protein kinases poses an enormous challenge to the design of cancer therapeutics. Additionally the high degree of structural conservation within the kinase superfamily often leads to inhibitors that exhibit little selectivity and substantial cross reactivity. This work investigates the conformational changes that accompany the binding of Gleevec, or imatinib mesylate, to the tyrosine kinases c-Kit and c-Abl. Our analysis is that this fit is driven, at least in part, by the need to exclude water from solvent-exposed backbone hydrogen bonds. Both experimental and molecular modeling studies of the active state inhibitor of the tyrosine kinase c-Abl indicate that solvent exclusion also plays a role in this system.
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pubmed:language |
eng
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pubmed:journal |
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pubmed:citationSubset |
IM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/9-hydroxyellipticine,
http://linkedlifedata.com/resource/pubmed/chemical/Antineoplastic Agents,
http://linkedlifedata.com/resource/pubmed/chemical/Ellipticines,
http://linkedlifedata.com/resource/pubmed/chemical/FGFR2 protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/Ligands,
http://linkedlifedata.com/resource/pubmed/chemical/Piperazines,
http://linkedlifedata.com/resource/pubmed/chemical/Protein Kinase Inhibitors,
http://linkedlifedata.com/resource/pubmed/chemical/Proto-Oncogene Proteins c-abl,
http://linkedlifedata.com/resource/pubmed/chemical/Proto-Oncogene Proteins c-kit,
http://linkedlifedata.com/resource/pubmed/chemical/Pyrimidines,
http://linkedlifedata.com/resource/pubmed/chemical/Receptor, Fibroblast Growth...,
http://linkedlifedata.com/resource/pubmed/chemical/Water,
http://linkedlifedata.com/resource/pubmed/chemical/imatinib
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pubmed:status |
MEDLINE
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pubmed:month |
Sep
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pubmed:issn |
1873-3468
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pubmed:author |
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pubmed:issnType |
Electronic
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pubmed:day |
3
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pubmed:volume |
583
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
2899-906
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pubmed:dateRevised |
2009-11-19
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pubmed:meshHeading |
pubmed-meshheading:19660459-Amino Acid Sequence,
pubmed-meshheading:19660459-Antineoplastic Agents,
pubmed-meshheading:19660459-Ellipticines,
pubmed-meshheading:19660459-Enzyme Activation,
pubmed-meshheading:19660459-Humans,
pubmed-meshheading:19660459-Hydrogen Bonding,
pubmed-meshheading:19660459-Ligands,
pubmed-meshheading:19660459-Models, Molecular,
pubmed-meshheading:19660459-Molecular Sequence Data,
pubmed-meshheading:19660459-Molecular Structure,
pubmed-meshheading:19660459-Mutation,
pubmed-meshheading:19660459-Piperazines,
pubmed-meshheading:19660459-Protein Kinase Inhibitors,
pubmed-meshheading:19660459-Protein Structure, Tertiary,
pubmed-meshheading:19660459-Proto-Oncogene Proteins c-abl,
pubmed-meshheading:19660459-Proto-Oncogene Proteins c-kit,
pubmed-meshheading:19660459-Pyrimidines,
pubmed-meshheading:19660459-Receptor, Fibroblast Growth Factor, Type 2,
pubmed-meshheading:19660459-Sequence Alignment,
pubmed-meshheading:19660459-Water
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pubmed:year |
2009
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pubmed:articleTitle |
Tyrosine kinase inhibition: Ligand binding and conformational change in c-Kit and c-Abl.
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pubmed:affiliation |
Department of Chemistry, St. Edward's University, Austin, TX 78704, USA. healy@stedwards.edu
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pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
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