2R5T

Crystal Structure of Inactive Serum and Glucocorticoid- Regulated Kinase 1 in Complex with AMP-PNP

Summary for 2R5T

• Entry DOI: 10.2210/pdb2r5t/pdb
• Descriptor: Serine/threonine-protein kinase Sgk1, MAGNESIUM ION, SULFATE ION, ... (5 entities in total)
• Functional Keywords: agc protein kinase, apoptosis, atp-binding, cytoplasm, endoplasmic reticulum, nucleotide-binding, nucleus, phosphorylation, serine/threonine-protein kinase, transferase, ubl conjugation
• Biological source: Homo sapiens (Human)
• Total number of polymer chains: 1
• Total formula weight: 42929.88

Authors

Zhao, B.,Lehr, R.,Smallwood, A.M.,Ho, T.F.,Maley, K.,Randall, T.,Head, M.S.,Koretke, K.K.,Schnackenberg, C.G. (deposition date: 2007-09-04, release date: 2008-09-09, Last modification date: 2024-02-21)

Primary citation

Zhao, B.,Lehr, R.,Smallwood, A.M.,Ho, T.F.,Maley, K.,Randall, T.,Head, M.S.,Koretke, K.K.,Schnackenberg, C.G.
Crystal structure of the kinase domain of serum and glucocorticoid-regulated kinase 1 in complex with AMP PNP.
Protein Sci., 16:2761-2769, 2007

PubMed Abstract: Serum and glucocorticoid-regulated kinase 1 (SGK1) is a serine/threonine protein kinase of the AGC family which participates in the control of epithelial ion transport and is implicated in proliferation and apoptosis. We report here the 1.9 A crystal structure of the catalytic domain of inactive human SGK1 in complex with AMP-PNP. SGK1 exists as a dimer formed by two intermolecular disulfide bonds between Cys258 in the activation loop and Cys193. Although most of the SGK1 structure closely resembles the common protein kinase fold, the structure around the active site is unique when compared to most protein kinases. The alphaC helix is not present in this inactive form of SGK1 crystal structure; instead, the segment corresponding to the C helix forms a beta-strand that is stabilized by the N-terminal segment of the activation loop through a short antiparallel beta-sheet. Since the differences from other kinases occur around the ATP binding site, this structure can provide valuable insight into the design of selective and highly potent ATP-competitive inhibitors of SGK1 kinase.

PubMed: 17965184
DOI: 10.1110/ps.073161707

Experimental method

X-RAY DIFFRACTION (1.9 Å)