1t4h
From Proteopedia
(New page: 200px<br /><applet load="1t4h" size="450" color="white" frame="true" align="right" spinBox="true" caption="1t4h, resolution 1.80Å" /> '''Crystal structure of...) |
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| - | [[Image:1t4h.jpg|left|200px]]<br /><applet load="1t4h" size=" | + | [[Image:1t4h.jpg|left|200px]]<br /><applet load="1t4h" size="350" color="white" frame="true" align="right" spinBox="true" |
caption="1t4h, resolution 1.80Å" /> | caption="1t4h, resolution 1.80Å" /> | ||
'''Crystal structure of the kinase domain of WNK1, a kinase that causes a hereditary form of hypertension'''<br /> | '''Crystal structure of the kinase domain of WNK1, a kinase that causes a hereditary form of hypertension'''<br /> | ||
==Overview== | ==Overview== | ||
| - | WNK kinases comprise a small group of unique serine/threonine protein | + | WNK kinases comprise a small group of unique serine/threonine protein kinases that have been genetically linked to pseudohypoaldosteronism type II, an autosomal dominant form of hypertension. Here we present the structure of the kinase domain of WNK1 at 1.8 A resolution, solved in a low activity conformation. A lysine residue (Lys-233) is found in the active site emanating from strand beta2 rather than strand beta3 as in other protein kinases. The activation loop adopts a unique well-folded inactive conformation. The conformations of the P+1 specificity pocket, the placement of the conserved active site threonine (Thr-386), and the exterior placement of helix C, contribute to the low activity state. By homology modeling, we identified two hydrophobic residues in the substrate-binding groove that contribute to substrate specificity. The structure of the WNK1 catalytic domain, with its unique active site, may help in the design of therapeutic reagents for the treatment of hypertension. |
==About this Structure== | ==About this Structure== | ||
| - | 1T4H is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Rattus_norvegicus Rattus norvegicus]. 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:// | + | 1T4H is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Rattus_norvegicus Rattus norvegicus]. 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=1T4H OCA]. |
==Reference== | ==Reference== | ||
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[[Category: Rattus norvegicus]] | [[Category: Rattus norvegicus]] | ||
[[Category: Single protein]] | [[Category: Single protein]] | ||
| - | [[Category: Cobb, M | + | [[Category: Cobb, M H.]] |
| - | [[Category: Goldsmith, E | + | [[Category: Goldsmith, E J.]] |
| - | [[Category: Lee, B | + | [[Category: Lee, B H.]] |
[[Category: Min, X.]] | [[Category: Min, X.]] | ||
[[Category: protein serine/threonine kinase]] | [[Category: protein serine/threonine kinase]] | ||
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[[Category: wnk1]] | [[Category: wnk1]] | ||
| - | ''Page seeded by [http:// | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 15:09:48 2008'' |
Revision as of 13:09, 21 February 2008
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Crystal structure of the kinase domain of WNK1, a kinase that causes a hereditary form of hypertension
Overview
WNK kinases comprise a small group of unique serine/threonine protein kinases that have been genetically linked to pseudohypoaldosteronism type II, an autosomal dominant form of hypertension. Here we present the structure of the kinase domain of WNK1 at 1.8 A resolution, solved in a low activity conformation. A lysine residue (Lys-233) is found in the active site emanating from strand beta2 rather than strand beta3 as in other protein kinases. The activation loop adopts a unique well-folded inactive conformation. The conformations of the P+1 specificity pocket, the placement of the conserved active site threonine (Thr-386), and the exterior placement of helix C, contribute to the low activity state. By homology modeling, we identified two hydrophobic residues in the substrate-binding groove that contribute to substrate specificity. The structure of the WNK1 catalytic domain, with its unique active site, may help in the design of therapeutic reagents for the treatment of hypertension.
About this Structure
1T4H is a Single protein structure of sequence from Rattus norvegicus. Active as Non-specific serine/threonine protein kinase, with EC number 2.7.11.1 Full crystallographic information is available from OCA.
Reference
Crystal structure of the kinase domain of WNK1, a kinase that causes a hereditary form of hypertension., Min X, Lee BH, Cobb MH, Goldsmith EJ, Structure. 2004 Jul;12(7):1303-11. PMID:15242606
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