2brh

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[[Image:2brh.gif|left|200px]]
[[Image:2brh.gif|left|200px]]
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{{Structure
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<!--
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|PDB= 2brh |SIZE=350|CAPTION= <scene name='initialview01'>2brh</scene>, resolution 2.10&Aring;
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The line below this paragraph, containing "STRUCTURE_2brh", creates the "Structure Box" on the page.
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|SITE= <scene name='pdbsite=AC1:Dfw+Binding+Site+For+Chain+A'>AC1</scene>
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You may change the PDB parameter (which sets the PDB file loaded into the applet)
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|LIGAND= <scene name='pdbligand=DFW:N-(5,6-DIPHENYLFURO[2,3-D]PYRIMIDIN-4-YL)GLYCINE'>DFW</scene>
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or the SCENE parameter (which sets the initial scene displayed when the page is loaded),
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|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>
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or leave the SCENE parameter empty for the default display.
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|GENE=
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-->
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|DOMAIN=
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{{STRUCTURE_2brh| PDB=2brh | SCENE= }}
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|RELATEDENTRY=
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|RESOURCES=<span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2brh FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2brh OCA], [http://www.ebi.ac.uk/pdbsum/2brh PDBsum], [http://www.rcsb.org/pdb/explore.do?structureId=2brh RCSB]</span>
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}}
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'''STRUCTURE-BASED DESIGN OF NOVEL CHK1 INHIBITORS: INSIGHTS INTO HYDROGEN BONDING AND PROTEIN-LIGAND AFFINITY'''
'''STRUCTURE-BASED DESIGN OF NOVEL CHK1 INHIBITORS: INSIGHTS INTO HYDROGEN BONDING AND PROTEIN-LIGAND AFFINITY'''
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[[Category: Robertson, A G.S.]]
[[Category: Robertson, A G.S.]]
[[Category: Surgenor, A E.]]
[[Category: Surgenor, A E.]]
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[[Category: atp-binding]]
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[[Category: Atp-binding]]
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[[Category: cell cycle]]
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[[Category: Cell cycle]]
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[[Category: dna damage]]
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[[Category: Dna damage]]
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[[Category: drug design]]
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[[Category: Drug design]]
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[[Category: furanopyrimidine]]
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[[Category: Furanopyrimidine]]
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[[Category: kinase]]
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[[Category: Kinase]]
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[[Category: molecular recognition]]
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[[Category: Molecular recognition]]
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[[Category: nuclear protein]]
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[[Category: Nuclear protein]]
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[[Category: oncology]]
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[[Category: Oncology]]
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[[Category: phosphorylation]]
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[[Category: Phosphorylation]]
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[[Category: polymorphism]]
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[[Category: Polymorphism]]
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[[Category: pyrrolopyrimidine]]
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[[Category: Pyrrolopyrimidine]]
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[[Category: serine/threonine-protein kinase]]
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[[Category: Serine/threonine-protein kinase]]
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[[Category: transferase]]
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[[Category: Transferase]]
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sat May 3 20:41:42 2008''
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Mon Mar 31 02:10:43 2008''
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Revision as of 17:41, 3 May 2008

Image:2brh.gif

Template:STRUCTURE 2brh

STRUCTURE-BASED DESIGN OF NOVEL CHK1 INHIBITORS: INSIGHTS INTO HYDROGEN BONDING AND PROTEIN-LIGAND AFFINITY


Overview

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 Structure

2BRH is a Single protein structure of sequence from Homo sapiens. Full crystallographic information is available from OCA.

Reference

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 Sat May 3 20:41:42 2008

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