2brb: Difference between revisions
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|PDB= 2brb |SIZE=350|CAPTION= <scene name='initialview01'>2brb</scene>, resolution 2.10Å | |PDB= 2brb |SIZE=350|CAPTION= <scene name='initialview01'>2brb</scene>, resolution 2.10Å | ||
|SITE= <scene name='pdbsite=AC1:So4+Binding+Site+For+Chain+A'>AC1</scene> | |SITE= <scene name='pdbsite=AC1:So4+Binding+Site+For+Chain+A'>AC1</scene> | ||
|LIGAND= | |LIGAND= <scene name='pdbligand=PFQ:2-[(5,6-DIPHENYLFURO[2,3-D]PYRIMIDIN-4-YL)AMINO]ETHANOL'>PFQ</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene> | ||
|ACTIVITY= [http://en.wikipedia.org/wiki/ | |ACTIVITY= <span class='plainlinks'>[http://en.wikipedia.org/wiki/Non-specific_serine/threonine_protein_kinase Non-specific serine/threonine protein kinase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.11.1 2.7.11.1] </span> | ||
|GENE= | |GENE= | ||
|DOMAIN= | |||
|RELATEDENTRY= | |||
|RESOURCES=<span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2brb FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2brb OCA], [http://www.ebi.ac.uk/pdbsum/2brb PDBsum], [http://www.rcsb.org/pdb/explore.do?structureId=2brb RCSB]</span> | |||
}} | }} | ||
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Structure-based design of novel Chk1 inhibitors: insights into hydrogen bonding and protein-ligand affinity., Foloppe N, Fisher LM, Howes R, Kierstan P, Potter A, Robertson AG, Surgenor AE, J Med Chem. 2005 Jun 30;48(13):4332-45. PMID:[http://www.ncbi.nlm.nih.gov/pubmed/15974586 15974586] | Structure-based design of novel Chk1 inhibitors: insights into hydrogen bonding and protein-ligand affinity., Foloppe N, Fisher LM, Howes R, Kierstan P, Potter A, Robertson AG, Surgenor AE, J Med Chem. 2005 Jun 30;48(13):4332-45. PMID:[http://www.ncbi.nlm.nih.gov/pubmed/15974586 15974586] | ||
[[Category: Homo sapiens]] | [[Category: Homo sapiens]] | ||
[[Category: Non-specific serine/threonine protein kinase]] | |||
[[Category: Single protein]] | [[Category: Single protein]] | ||
[[Category: Fisher, L M.]] | [[Category: Fisher, L M.]] | ||
[[Category: Foloppe, N.]] | [[Category: Foloppe, N.]] | ||
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[[Category: Robertson, A G.S.]] | [[Category: Robertson, A G.S.]] | ||
[[Category: Surgenor, A E.]] | [[Category: Surgenor, A E.]] | ||
[[Category: drug design]] | [[Category: drug design]] | ||
[[Category: furanopyrimidine]] | [[Category: furanopyrimidine]] | ||
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[[Category: transferase]] | [[Category: transferase]] | ||
''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Mon Mar 31 02:10:33 2008'' | ||
Revision as of 02:10, 31 March 2008
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| , resolution 2.10Å | |||||||
|---|---|---|---|---|---|---|---|
| Sites: | |||||||
| Ligands: | , | ||||||
| Activity: | Non-specific serine/threonine protein kinase, with EC number 2.7.11.1 | ||||||
| Resources: | FirstGlance, OCA, PDBsum, RCSB | ||||||
| Coordinates: | save as pdb, mmCIF, xml | ||||||
STRUCTURE-BASED DESIGN OF NOVEL CHK1 INHIBITORS: INSIGHTS INTO HYDROGEN BONDING AND PROTEIN-LIGAND AFFINITY
OverviewOverview
We report the discovery, synthesis, and crystallographic binding mode of novel furanopyrimidine and pyrrolopyrimidine inhibitors of the Chk1 kinase, an oncology target. These inhibitors are synthetically tractable and inhibit Chk1 by competing for its ATP site. A chronological account allows an objective comparison of modeled compound docking modes to the subsequently obtained crystal structures. The comparison provides insights regarding the interpretation of modeling results, in relationship to the multiple reasonable docking modes which may be obtained in a kinase-ATP site. The crystal structures were used to guide medicinal chemistry efforts. This led to a thorough characterization of a pair of ligand-protein complexes which differ by a single hydrogen bond. An analysis indicates that this hydrogen bond is expected to contribute a fraction of the 10-fold change in binding affinity, adding a valuable observation to the debate about the energetic role of hydrogen bonding in molecular recognition.
About this StructureAbout this Structure
2BRB is a Single protein structure of sequence from Homo sapiens. Full crystallographic information is available from OCA.
ReferenceReference
Structure-based design of novel Chk1 inhibitors: insights into hydrogen bonding and protein-ligand affinity., Foloppe N, Fisher LM, Howes R, Kierstan P, Potter A, Robertson AG, Surgenor AE, J Med Chem. 2005 Jun 30;48(13):4332-45. PMID:15974586
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