2brb: Difference between revisions
No edit summary |
No edit summary |
||
| Line 1: | Line 1: | ||
[[Image:2brb.gif|left|200px]]<br /> | [[Image:2brb.gif|left|200px]]<br /><applet load="2brb" size="450" color="white" frame="true" align="right" spinBox="true" | ||
<applet load="2brb" size="450" color="white" frame="true" align="right" spinBox="true" | |||
caption="2brb, resolution 2.10Å" /> | caption="2brb, resolution 2.10Å" /> | ||
'''STRUCTURE-BASED DESIGN OF NOVEL CHK1 INHIBITORS: INSIGHTS INTO HYDROGEN BONDING AND PROTEIN-LIGAND AFFINITY'''<br /> | '''STRUCTURE-BASED DESIGN OF NOVEL CHK1 INHIBITORS: INSIGHTS INTO HYDROGEN BONDING AND PROTEIN-LIGAND AFFINITY'''<br /> | ||
| Line 8: | Line 7: | ||
==About this Structure== | ==About this Structure== | ||
2BRB is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] with SO4 and PFQ as [http://en.wikipedia.org/wiki/ligands ligands]. Active as [http://en.wikipedia.org/wiki/Transferred_entry:_2.7.11.1 Transferred entry: 2.7.11.1], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.1.37 2.7.1.37] | 2BRB is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] with SO4 and PFQ as [http://en.wikipedia.org/wiki/ligands ligands]. Active as [http://en.wikipedia.org/wiki/Transferred_entry:_2.7.11.1 Transferred entry: 2.7.11.1], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.1.37 2.7.1.37] Known structural/functional Site: <scene name='pdbsite=AC1:So4 Binding Site For Chain A'>AC1</scene>. Full crystallographic information is available from [http://ispc.weizmann.ac.il/oca-bin/ocashort?id=2BRB OCA]. | ||
==Reference== | ==Reference== | ||
| Line 31: | Line 30: | ||
[[Category: transferase]] | [[Category: transferase]] | ||
''Page seeded by [http://ispc.weizmann.ac.il/oca OCA ] on | ''Page seeded by [http://ispc.weizmann.ac.il/oca OCA ] on Tue Dec 18 18:56:10 2007'' | ||
Revision as of 19:46, 18 December 2007
|
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 with SO4 and PFQ as ligands. Active as Transferred entry: 2.7.11.1, with EC number 2.7.1.37 Known structural/functional Site: . 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
Page seeded by OCA on Tue Dec 18 18:56:10 2007