2bba: Difference between revisions

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Crystal Structure and Thermodynamic Characterization of the EphB4 Receptor in Complex with an ephrin-B2 Antagonist Peptide Reveals the Determinants for Receptor Specificity

OverviewOverview

The Eph receptor tyrosine kinases and their ligands, the ephrins, regulate numerous biological processes in developing and adult tissues and have been implicated in cancer progression and in pathological forms of angiogenesis. We report the crystal structure of the EphB4 receptor in complex with a highly specific antagonistic peptide at a resolution of 1.65 angstroms. The peptide is situated in a hydrophobic cleft of EphB4 corresponding to the cleft in EphB2 occupied by the ephrin-B2 G-H loop, consistent with its antagonistic properties. Structural analysis identifies several residues within the EphB4 binding cleft that likely determine the ligand specificity of this receptor, while isothermal titration calorimetry experiments with truncated forms of the peptide define the amino acid residues of the peptide that are critical for receptor binding. These studies reveal structural features that will aid drug discovery initiatives to develop EphB4 antagonists for therapeutic applications.

About this StructureAbout this Structure

2BBA is a Single protein structure of sequence from Homo sapiens with as ligand. Active as Transferase, with EC number and 2.7.10.2 2.7.10.1 and 2.7.10.2 Full crystallographic information is available from OCA.

ReferenceReference

Structure and thermodynamic characterization of the EphB4/Ephrin-B2 antagonist peptide complex reveals the determinants for receptor specificity., Chrencik JE, Brooun A, Recht MI, Kraus ML, Koolpe M, Kolatkar AR, Bruce RH, Martiny-Baron G, Widmer H, Pasquale EB, Kuhn P, Structure. 2006 Feb;14(2):321-30. PMID:16472751

Page seeded by OCA on Thu Feb 21 16:35:58 2008

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OCA

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-[[Image:2bba.gif|left|200px]]<br />
+[[Image:2bba.gif|left|200px]]<br /><applet load="2bba" size="350" color="white" frame="true" align="right" spinBox="true"
-<applet load="2bba" size="450" color="white" frame="true" align="right" spinBox="true"
 caption="2bba, resolution 1.65&Aring;" />
 '''Crystal Structure and Thermodynamic Characterization of the EphB4 Receptor in Complex with an ephrin-B2 Antagonist Peptide Reveals the Determinants for Receptor Specificity'''<br />
 ==Overview==
-The Eph receptor tyrosine kinases and their ligands, the ephrins, regulate, numerous biological processes in developing and adult tissues and have, been implicated in cancer progression and in pathological forms of, angiogenesis. We report the crystal structure of the EphB4 receptor in, complex with a highly specific antagonistic peptide at a resolution of, 1.65 angstroms. The peptide is situated in a hydrophobic cleft of EphB4, corresponding to the cleft in EphB2 occupied by the ephrin-B2 G-H loop, consistent with its antagonistic properties. Structural analysis, identifies several residues within the EphB4 binding cleft that likely, determine the ligand specificity of this receptor, while isothermal, titration calorimetry experiments with truncated forms of the peptide, define the amino acid residues of the peptide that are critical for, receptor binding. These studies reveal structural features that will aid, drug discovery initiatives to develop EphB4 antagonists for therapeutic, applications.
+The Eph receptor tyrosine kinases and their ligands, the ephrins, regulate numerous biological processes in developing and adult tissues and have been implicated in cancer progression and in pathological forms of angiogenesis. We report the crystal structure of the EphB4 receptor in complex with a highly specific antagonistic peptide at a resolution of 1.65 angstroms. The peptide is situated in a hydrophobic cleft of EphB4 corresponding to the cleft in EphB2 occupied by the ephrin-B2 G-H loop, consistent with its antagonistic properties. Structural analysis identifies several residues within the EphB4 binding cleft that likely determine the ligand specificity of this receptor, while isothermal titration calorimetry experiments with truncated forms of the peptide define the amino acid residues of the peptide that are critical for receptor binding. These studies reveal structural features that will aid drug discovery initiatives to develop EphB4 antagonists for therapeutic applications.
 ==About this Structure==
-BBA 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 as [http://en.wikipedia.org/wiki/ligand ligand]. Active as [http://en.wikipedia.org/wiki/Transferase Transferase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.10.1 and 2.7.10.2 2.7.10.1 and 2.7.10.2] Full crystallographic information is available from [http://ispc.weizmann.ac.il/oca-bin/ocashort?id=2BBA OCA].
+BBA 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 <scene name='pdbligand=SO4:'>SO4</scene> as [http://en.wikipedia.org/wiki/ligand ligand]. Active as [http://en.wikipedia.org/wiki/Transferase Transferase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.10.1 and 2.7.10.2 2.7.10.1 and 2.7.10.2] Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2BBA OCA].
 ==Reference==
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 [[Category: Single protein]]
 [[Category: Transferase]]
-[[Category: Chrencik, J.E.]]
+[[Category: Chrencik, J E.]]
 [[Category: Kuhn, P.]]
 [[Category: SO4]]
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 [[Category: tumorigenesis]]
-''Page seeded by [http://ispc.weizmann.ac.il/oca OCA ] on Mon Nov 12 21:00:34 2007''
+''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 16:35:58 2008''