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Crystal structure of the kinase domain of serum and glucocorticoid-regulated kinase 1 in complex with AMP PNP.

Zhao B, Lehr R, Smallwood AM, Ho TF, Maley K, Randall T, Head MS, Koretke KK, Schnackenberg CG
Protein Sci 16 2761-9 (2007)
Cited: 36 times
EuropePMC logo PMID: 17965184

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.

Reviews - 2r5t mentioned but not cited (1)

  1. Serum and glucocorticoid-regulated kinase 1: Structure, biological functions, and its inhibitors. Jang H, Park Y, Jang J. Front Pharmacol 13 1036844 (2022)

Articles - 2r5t mentioned but not cited (16)

  1. Crystal structure of the kinase domain of serum and glucocorticoid-regulated kinase 1 in complex with AMP PNP. Zhao B, Lehr R, Smallwood AM, Ho TF, Maley K, Randall T, Head MS, Koretke KK, Schnackenberg CG. Protein Sci 16 2761-2769 (2007)
  2. Regulation of a third conserved phosphorylation site in SGK1. Chen W, Chen Y, Xu BE, Juang YC, Stippec S, Zhao Y, Cobb MH. J Biol Chem 284 3453-3460 (2009)
  3. Structural insight into nucleotide recognition by human death-associated protein kinase. McNamara LK, Watterson DM, Brunzelle JS. Acta Crystallogr D Biol Crystallogr 65 241-248 (2009)
  4. Virtual Screening Approach to Identify High-Affinity Inhibitors of Serum and Glucocorticoid-Regulated Kinase 1 among Bioactive Natural Products: Combined Molecular Docking and Simulation Studies. Mohammad T, Siddiqui S, Shamsi A, Alajmi MF, Hussain A, Islam A, Ahmad F, Hassan MI. Molecules 25 (2020)
  5. Discovery of Herbacetin as a Novel SGK1 Inhibitor to Alleviate Myocardial Hypertrophy. Zhang S, Wang Y, Yu M, Shang Y, Chang Y, Zhao H, Kang Y, Zhao L, Xu L, Zhao X, Difrancesco D, Baruscotti M, Wang Y. Adv Sci (Weinh) 9 e2101485 (2022)
  6. Inhibition of serum and glucocorticoid regulated kinase-1 as novel therapy for cardiac arrhythmia disorders. Bezzerides VJ, Zhang A, Xiao L, Simonson B, Khedkar SA, Baba S, Ottaviano F, Lynch S, Hessler K, Rigby AC, Milan D, Das S, Rosenzweig A. Sci Rep 7 346 (2017)
  7. Identification, structure modification, and characterization of potential small-molecule SGK3 inhibitors with novel scaffolds. Gong GQ, Wang K, Dai XC, Zhou Y, Basnet R, Chen Y, Yang DH, Lee WJ, Buchanan CM, Flanagan JU, Shepherd PR, Chen Y, Wang MW. Acta Pharmacol Sin 39 1902-1912 (2018)
  8. Suppressor screening reveals common kleisin-hinge interaction in condensin and cohesin, but different modes of regulation. Xu X, Yanagida M. Proc Natl Acad Sci U S A 116 10889-10898 (2019)
  9. Impact of Deleterious Mutations on Structure, Function and Stability of Serum/Glucocorticoid Regulated Kinase 1: A Gene to Diseases Correlation. AlAjmi MF, Khan S, Choudhury A, Mohammad T, Noor S, Hussain A, Lu W, Eapen MS, Chimankar V, Hansbro PM, Sohal SS, Elasbali AM, Hassan MI. Front Mol Biosci 8 780284 (2021)
  10. TOR Complex 2- independent mutations in the regulatory PIF pocket of Gad8AKT1/SGK1 define separate branches of the stress response mechanisms in fission yeast. Pataki E, Simhaev L, Engel H, Cohen A, Kupiec M, Weisman R. PLoS Genet 16 e1009196 (2020)
  11. The dipeptidyl peptidase IV inhibitors vildagliptin and K-579 inhibit a phospholipase C: a case of promiscuous scaffolds in proteins. Chakraborty S, Rendón-Ramírez A, Ásgeirsson B, Dutta M, Ghosh AS, Oda M, Venkatramani R, Rao BJ, Dandekar AM, Goñi FM. F1000Res 2 286 (2013)
  12. Murine isoforms of UDP-GlcNAc 2-epimerase/ManNAc kinase: Secondary structures, expression profiles, and response to ManNAc therapy. Yardeni T, Jacobs K, Niethamer TK, Ciccone C, Anikster Y, Kurochkina N, Gahl WA, Huizing M. Glycoconj J 30 609-618 (2013)
  13. RSK1 vs. RSK2 Inhibitory Activity of the Marine β-Carboline Alkaloid Manzamine A: A Biochemical, Cervical Cancer Protein Expression, and Computational Study. Mayer AMS, Hall ML, Lach J, Clifford J, Chandrasena K, Canton C, Kontoyianni M, Choo YM, Karan D, Hamann MT. Mar Drugs 19 506 (2021)
  14. Identification of a new structural family of SGK1 inhibitors as potential neuroprotective agents. Maestro I, Madruga E, Boya P, Martínez A. J Enzyme Inhib Med Chem 38 2153841 (2023)
  15. Identification of enzymes that have helminth-specific active sites and are required for Rhodoquinone-dependent metabolism as targets for new anthelmintics. Lautens MJ, Tan JH, Serrat X, Del Borrello S, Schertzberg MR, Fraser AG. PLoS Negl Trop Dis 15 e0009991 (2021)
  16. Luteolin inhibits triple-negative breast cancer by inducing apoptosis and autophagy through SGK1-FOXO3a-BNIP3 signaling. Wu L, Lin Y, Gao S, Wang Y, Pan H, Wang Z, Pozzolini M, Yang F, Zhang H, Yang Y, Xiao L, Xu Y. Front Pharmacol 14 1200843 (2023)


Reviews citing this publication (6)

  1. The physiological impact of the serum and glucocorticoid-inducible kinase SGK1. Lang F, Artunc F, Vallon V. Curr Opin Nephrol Hypertens 18 439-448 (2009)
  2. AGC protein kinases: from structural mechanism of regulation to allosteric drug development for the treatment of human diseases. Arencibia JM, Pastor-Flores D, Bauer AF, Schulze JO, Biondi RM. Biochim Biophys Acta 1834 1302-1321 (2013)
  3. Targeting SGK1 in diabetes. Lang F, Görlach A, Vallon V. Expert Opin Ther Targets 13 1303-1311 (2009)
  4. Serum and Glucocorticoid Regulated Kinase 1 in Sodium Homeostasis. Lou Y, Zhang F, Luo Y, Wang L, Huang S, Jin F. Int J Mol Sci 17 (2016)
  5. Serum and glucocorticoid inducible protein kinases (SGKs): a potential target for cancer intervention. Basnet R, Gong GQ, Li C, Wang MW. Acta Pharm Sin B 8 767-771 (2018)
  6. The Enigmatic Role of Serum & Glucocorticoid Inducible Kinase 1 in the Endometrium. Lang F, Rajaxavier J, Singh Y, Brucker SY, Salker MS. Front Cell Dev Biol 8 556543 (2020)

Articles citing this publication (13)

  1. A single polymorphic amino acid on Toxoplasma gondii kinase ROP16 determines the direct and strain-specific activation of Stat3. Yamamoto M, Standley DM, Takashima S, Saiga H, Okuyama M, Kayama H, Kubo E, Ito H, Takaura M, Matsuda T, Soldati-Favre D, Takeda K. J Exp Med 206 2747-2760 (2009)
  2. PDK1-SGK1 Signaling Sustains AKT-Independent mTORC1 Activation and Confers Resistance to PI3Kα Inhibition. Castel P, Ellis H, Bago R, Toska E, Razavi P, Carmona FJ, Kannan S, Verma CS, Dickler M, Chandarlapaty S, Brogi E, Alessi DR, Baselga J, Scaltriti M. Cancer Cell 30 229-242 (2016)
  3. PKC maturation is promoted by nucleotide pocket occupation independently of intrinsic kinase activity. Cameron AJ, Escribano C, Saurin AT, Kostelecky B, Parker PJ. Nat Struct Mol Biol 16 624-630 (2009)
  4. Structure and allosteric effects of low-molecular-weight activators on the protein kinase PDK1. Hindie V, Stroba A, Zhang H, Lopez-Garcia LA, Idrissova L, Zeuzem S, Hirschberg D, Schaeffer F, Jørgensen TJ, Engel M, Alzari PM, Biondi RM. Nat Chem Biol 5 758-764 (2009)
  5. Structural basis of human p70 ribosomal S6 kinase-1 regulation by activation loop phosphorylation. Sunami T, Byrne N, Diehl RE, Funabashi K, Hall DL, Ikuta M, Patel SB, Shipman JM, Smith RF, Takahashi I, Zugay-Murphy J, Iwasawa Y, Lumb KJ, Munshi SK, Sharma S. J Biol Chem 285 4587-4594 (2010)
  6. Discovery of N-[4-(1H-Pyrazolo[3,4-b]pyrazin-6-yl)-phenyl]-sulfonamides as Highly Active and Selective SGK1 Inhibitors. Halland N, Schmidt F, Weiss T, Saas J, Li Z, Czech J, Dreyer M, Hofmeister A, Mertsch K, Dietz U, Strübing C, Nazare M. ACS Med Chem Lett 6 73-78 (2015)
  7. Identification, tissue distribution, and molecular modeling of novel human isoforms of the key enzyme in sialic acid synthesis, UDP-GlcNAc 2-epimerase/ManNAc kinase. Yardeni T, Choekyi T, Jacobs K, Ciccone C, Patzel K, Anikster Y, Gahl WA, Kurochkina N, Huizing M. Biochemistry 50 8914-8925 (2011)
  8. Regulation of the interaction between protein kinase C-related protein kinase 2 (PRK2) and its upstream kinase, 3-phosphoinositide-dependent protein kinase 1 (PDK1). Dettori R, Sonzogni S, Meyer L, Lopez-Garcia LA, Morrice NA, Zeuzem S, Engel M, Piiper A, Neimanis S, Frödin M, Biondi RM. J Biol Chem 284 30318-30327 (2009)
  9. Structural diversity of the active N-terminal kinase domain of p90 ribosomal S6 kinase 2. Malakhova M, Kurinov I, Liu K, Zheng D, D'Angelo I, Shim JH, Steinman V, Bode AM, Dong Z. PLoS One 4 e8044 (2009)
  10. The Stress-Sensing TORC2 Complex Activates Yeast AGC-Family Protein Kinase Ypk1 at Multiple Novel Sites. Leskoske KL, Roelants FM, Martinez Marshall MN, Hill JM, Thorner J. Genetics 207 179-195 (2017)
  11. Structure of dystrophia myotonica protein kinase. Elkins JM, Amos A, Niesen FH, Pike AC, Fedorov O, Knapp S. Protein Sci 18 782-791 (2009)
  12. Estradiol Suppresses TLR4-triggered Apoptosis of Decidual Stromal Cells and Drives an Anti-inflammatory TH2 Shift by Activating SGK1. Lou Y, Hu M, Wang Q, Yuan M, Wang N, Le F, Li L, Huang S, Wang L, Xu X, Jin F. Int J Biol Sci 13 434-448 (2017)
  13. Structural insights into Ras regulation by SIN1. Zheng Y, Ding L, Meng X, Potter M, Kearney AL, Zhang J, Sun J, James DE, Yang G, Zhou C. Proc Natl Acad Sci U S A 119 e2119990119 (2022)


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