1xh4

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[[Image:1xh4.gif|left|200px]]<br /><applet load="1xh4" size="350" color="white" frame="true" align="right" spinBox="true"
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[[Image:1xh4.gif|left|200px]]
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caption="1xh4, resolution 2.45&Aring;" />
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'''Crystal Structures of Protein Kinase B Selective Inhibitors in Complex with Protein Kinase A and Mutants'''<br />
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{{Structure
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|PDB= 1xh4 |SIZE=350|CAPTION= <scene name='initialview01'>1xh4</scene>, resolution 2.45&Aring;
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|SITE=
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|LIGAND= <scene name='pdbligand=R69:N-[4-({4-[5-(DIMETHYLAMINO)-2-HYDROXYBENZOYL]BENZOYL}AMINO)AZEPAN-3-YL]ISONICOTINAMIDE'>R69</scene>
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|ACTIVITY= [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]
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|GENE= PRKACA ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9913 Bos taurus])
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}}
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'''Crystal Structures of Protein Kinase B Selective Inhibitors in Complex with Protein Kinase A and Mutants'''
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==Overview==
==Overview==
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==About this Structure==
==About this Structure==
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1XH4 is a [http://en.wikipedia.org/wiki/Protein_complex Protein complex] structure of sequences from [http://en.wikipedia.org/wiki/Bos_taurus Bos taurus] with <scene name='pdbligand=R69:'>R69</scene> as [http://en.wikipedia.org/wiki/ligand ligand]. Active as [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] Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1XH4 OCA].
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1XH4 is a [[Protein complex]] structure of sequences from [http://en.wikipedia.org/wiki/Bos_taurus Bos taurus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1XH4 OCA].
==Reference==
==Reference==
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Design and crystal structures of protein kinase B-selective inhibitors in complex with protein kinase A and mutants., Breitenlechner CB, Friebe WG, Brunet E, Werner G, Graul K, Thomas U, Kunkele KP, Schafer W, Gassel M, Bossemeyer D, Huber R, Engh RA, Masjost B, J Med Chem. 2005 Jan 13;48(1):163-70. PMID:[http://ispc.weizmann.ac.il//pmbin/getpm?pmid=15634010 15634010]
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Design and crystal structures of protein kinase B-selective inhibitors in complex with protein kinase A and mutants., Breitenlechner CB, Friebe WG, Brunet E, Werner G, Graul K, Thomas U, Kunkele KP, Schafer W, Gassel M, Bossemeyer D, Huber R, Engh RA, Masjost B, J Med Chem. 2005 Jan 13;48(1):163-70. PMID:[http://www.ncbi.nlm.nih.gov/pubmed/15634010 15634010]
[[Category: Bos taurus]]
[[Category: Bos taurus]]
[[Category: Non-specific serine/threonine protein kinase]]
[[Category: Non-specific serine/threonine protein kinase]]
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[[Category: serine/threonine-protein kinase]]
[[Category: serine/threonine-protein kinase]]
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 15:54:43 2008''
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Mar 20 15:09:44 2008''

Revision as of 13:09, 20 March 2008

Image:1xh4.gif


PDB ID 1xh4

Drag the structure with the mouse to rotate
, resolution 2.45Å
Ligands:
Gene: PRKACA (Bos taurus)
Activity: Non-specific serine/threonine protein kinase, with EC number 2.7.11.1
Coordinates: save as pdb, mmCIF, xml



Crystal Structures of Protein Kinase B Selective Inhibitors in Complex with Protein Kinase A and Mutants


Overview

Protein kinase B (PKB)-selective inhibitors were designed, synthesized, and cocrystallized using the AGC kinase family protein kinase A (PKA, often called cAMP-dependent protein kinase); PKA has been used as a surrogate for other members of this family and indeed for protein kinases in general. The high homology between PKA and PKB includes very similar ATP binding sites and hence similar binding pockets for inhibitors, with only few amino acids that differ between the two kinases. A series of these sites were mutated in PKA in order to improve the surrogate model for a design of PKB-selective inhibitors. Namely, the PKA to PKB exchanges F187L and Q84E enable the design of the selective inhibitors described herein which mimic ATP but extend further into a site not occupied by ATP. In this pocket, selectivity over PKA can be achieved by the introduction of bulkier substituents. Analysis of the cocrystal structures and binding studies were performed to rationalize the selectivity and improve the design.

About this Structure

1XH4 is a Protein complex structure of sequences from Bos taurus. Full crystallographic information is available from OCA.

Reference

Design and crystal structures of protein kinase B-selective inhibitors in complex with protein kinase A and mutants., Breitenlechner CB, Friebe WG, Brunet E, Werner G, Graul K, Thomas U, Kunkele KP, Schafer W, Gassel M, Bossemeyer D, Huber R, Engh RA, Masjost B, J Med Chem. 2005 Jan 13;48(1):163-70. PMID:15634010

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