TOR Complex 2- independent mutations in the regulatory PIF pocket of Gad8AKT1/SGK1 define separate branches of the stress response mechanisms in fission yeast
Autoři:
Emese Pataki aff001; LubFtablea Simhaev aff002; Hamutal Engel aff002; Adiel Cohen aff001; Martin Kupiec aff003; Ronit Weisman aff001; Luba Simhaev aff002
Působiště autorů:
Department of Natural and Life Sciences, The Open University of Israel, Ra'anana, Israel
aff001; Blavatnik Center for Drug Discovery, Tel Aviv University, Tel Aviv, Israel
aff002; The Shmunis School of Biomedicine & Cancer Research, Tel Aviv University, Ramat Aviv, Tel Aviv, Israel
aff003
Vyšlo v časopise:
TOR Complex 2- independent mutations in the regulatory PIF pocket of Gad8AKT1/SGK1 define separate branches of the stress response mechanisms in fission yeast. PLoS Genet 16(11): e32767. doi:10.1371/journal.pgen.1009196
Kategorie:
Research Article
doi:
https://doi.org/10.1371/journal.pgen.1009196
Souhrn
The Target of rapamycin (TOR) protein kinase forms part of TOR complex 1 (TORC1) and TOR complex 2 (TORC2), two multi-subunit protein complexes that regulate growth, proliferation, survival and developmental processes by phosphorylation and activation of AGC-family kinases. In the fission yeast, Schizosaccharomyces pombe, TORC2 and its target, the AGC kinase Gad8 (an orthologue of human AKT or SGK1) are required for viability under stress conditions and for developmental processes in response to starvation cues. In this study, we describe the isolation of gad8 mutant alleles that bypass the requirement for TORC2 and reveal a separation of function of TORC2 and Gad8 under stress conditions. In particular, osmotic and nutritional stress responses appear to form a separate branch from genotoxic stress responses downstream of TORC2-Gad8. Interestingly, TORC2-independent mutations map into the regulatory PIF pocket of Gad8, a highly conserved motif in AGC kinases that regulates substrate binding in PDK1 (phosphoinositide dependent kinase-1) and kinase activity in several AGC kinases. Gad8 activation is thought to require a two-step mechanism, in which phosphorylation by TORC2 allows further phosphorylation and activation by Ksg1 (an orthologue of PDK1). We focus on the Gad8-K263C mutation and demonstrate that it renders the Gad8 kinase activity independent of TORC2 in vitro and independent of the phosphorylation sites of TORC2 in vivo. Molecular dynamics simulations of Gad8-K263C revealed abnormal high flexibility at T387, the phosphorylation site for Ksg1, suggesting a mechanism for the TORC2-independent Gad8 activity. Significantly, the K263 residue is highly conserved in the family of AGC-kinases, which may suggest a general way of keeping their activity in check when acting downstream of TOR complexes.
Klíčová slova:
DNA damage – Mutation – Osmotic shock – Phosphorylation – Point mutation – Polymerase chain reaction – Protein kinases – Schizosaccharomyces pombe
Zdroje
1. Luo Y, Xu W, Li G, Cui W. Weighing In on mTOR Complex 2 Signaling: The Expanding Role in Cell Metabolism. Oxidative medicine and cellular longevity. 2018;2018:7838647. doi: 10.1155/2018/7838647 30510625; PubMed Central PMCID: PMC6232796.
2. Kim J, Guan KL. mTOR as a central hub of nutrient signalling and cell growth. Nature cell biology. 2019;21(1):63–71. doi: 10.1038/s41556-018-0205-1 30602761.
3. Liu GY, Sabatini DM. mTOR at the nexus of nutrition, growth, ageing and disease. Nat Rev Mol Cell Biol. 2020;21(4):183–203. Epub 2020/01/16. doi: 10.1038/s41580-019-0199-y 31937935; PubMed Central PMCID: PMC7102936.
4. Loewith R, Jacinto E, Wullschleger S, Lorberg A, Crespo JL, Bonenfant D, et al. Two TOR Complexes, Only One of which Is Rapamycin Sensitive, Have Distinct Roles in Cell Growth Control. Molecular cell. 2002;10(3):457–68. doi: 10.1016/s1097-2765(02)00636-6 12408816
5. Loewith R, Hall MN. Target of rapamycin (TOR) in nutrient signaling and growth control. Genetics. 2011;189(4):1177–201. Epub 2011/12/17. doi: 10.1534/genetics.111.133363 189/4/1177 [pii]. 22174183; PubMed Central PMCID: PMC3241408.
6. Ben-Sahra I, Manning BD. mTORC1 signaling and the metabolic control of cell growth. Current opinion in cell biology. 2017;45:72–82. doi: 10.1016/j.ceb.2017.02.012 PubMed Central PMCID: PMC5545101. 28411448
7. Weisman R. Target of Rapamycin (TOR) Regulates Growth in Response to Nutritional Signals. Microbiol Spectr. 2016;4(5). doi: 10.1128/microbiolspec.FUNK-0006-2016 27763256.
8. Masui K, Harachi M, Cavenee WK, Mischel PS, Shibata N. mTOR complex 2 is an integrator of cancer metabolism and epigenetics. Cancer Lett. 2020;478:1–7. Epub 2020/03/08. doi: 10.1016/j.canlet.2020.03.001 32145344.
9. Laribee RN, Weisman R. Nuclear Functions of TOR: Impact on Transcription and the Epigenome. Genes (Basel). 2020;11(6). Epub 2020/06/14. doi: 10.3390/genes11060641 32532005.
10. Jacinto E, Lorberg A. TOR regulation of AGC kinases in yeast and mammals. Biochem J. 2008;410(1):19–37. doi: 10.1042/BJ20071518 18215152.
11. Burnett PE, Barrow RK, Cohen NA, Snyder SH, Sabatini DM. RAFT1 phosphorylation of the translational regulators p70 S6 kinase and 4E-BP1. Proceedings of the National Academy of Sciences of the United States of America. 1998;95(4):1432–7. doi: 10.1073/pnas.95.4.1432 9465032.
12. Saitoh M, Pullen N, Brennan P, Cantrell D, Dennis PB, Thomas G. Regulation of an activated S6 kinase 1 variant reveals a novel mammalian target of rapamycin phosphorylation site. The Journal of biological chemistry. 2002;277(22):20104–12. doi: 10.1074/jbc.M201745200 11914378
13. Isotani S, Hara K, Tokunaga C, Inoue H, Avruch J, Yonezawa K. Immunopurified mammalian target of rapamycin phosphorylates and activates p70 S6 kinase alpha in vitro. The Journal of biological chemistry. 1999;274(48):34493–8. Epub 1999/11/24. doi: 10.1074/jbc.274.48.34493 10567431.
14. Urban J, Soulard A, Huber A, Lippman S, Mukhopadhyay D, Deloche O, et al. Sch9 is a major target of TORC1 in Saccharomyces cerevisiae. Molecular cell. 2007;26(5):663–74. Epub 2007/06/15. doi: 10.1016/j.molcel.2007.04.020 17560372.
15. Nakashima A, Otsubo Y, Yamashita A, Sato T, Yamamoto M, Tamanoi F. Psk1, an AGC kinase family member in fission yeast, is directly phosphorylated and controlled by TORC1 and functions as S6 kinase. Journal of cell science. 2012;125(Pt 23):5840–9. Epub 2012/09/15. jcs.111146 [pii]. doi: 10.1242/jcs.111146 22976295.
16. Sarbassov DD, Guertin DA, Ali SM, Sabatini DM. Phosphorylation and regulation of Akt/PKB by the rictor-mTOR complex. Science. 2005;307(5712):1098–101. doi: 10.1126/science.1106148 15718470.
17. Ikenoue T, Inoki K, Yang Q, Zhou X, Guan KL. Essential function of TORC2 in PKC and Akt turn motif phosphorylation, maturation and signalling. The EMBO journal. 2008;27(14):1919–31. Epub 2008/06/21. emboj2008119 [pii]. doi: 10.1038/emboj.2008.119 18566587.
18. Facchinetti V, Ouyang W, Wei H, Soto N, Lazorchak A, Gould C, et al. The mammalian target of rapamycin complex 2 controls folding and stability of Akt and protein kinase C. The EMBO journal. 2008;27(14):1932–43. Epub 2008/06/21. emboj2008120 [pii]. doi: 10.1038/emboj.2008.120 18566586.
19. Garcia-Martinez JM, Alessi DR. mTOR complex 2 (mTORC2) controls hydrophobic motif phosphorylation and activation of serum- and glucocorticoid-induced protein kinase 1 (SGK1). Biochem J. 2008;416(3):375–85. doi: 10.1042/BJ20081668 18925875.
20. Sarbassov DD, Ali SM, Kim DH, Guertin DA, Latek RR, Erdjument-Bromage H, et al. Rictor, a novel binding partner of mTOR, defines a rapamycin-insensitive and raptor-independent pathway that regulates the cytoskeleton. Current biology: CB. 2004;14(14):1296–302. doi: 10.1016/j.cub.2004.06.054 15268862.
21. Guertin DA, Stevens DM, Thoreen CC, Burds AA, Kalaany NY, Moffat J, et al. Ablation in mice of the mTORC components raptor, rictor, or mLST8 reveals that mTORC2 is required for signaling to Akt-FOXO and PKCalpha, but not S6K1. Dev Cell. 2006;11(6):859–71. Epub 2006/12/05. doi: 10.1016/j.devcel.2006.10.007 17141160.
22. Schmidt A, Kunz J, Hall MN. TOR2 is required for organization of the actin cytoskeleton in yeast. Proceedings of the National Academy of Sciences of the United States of America. 1996;93(24):13780–5. doi: 10.1073/pnas.93.24.13780 8943012
23. deHart AK, Schnell JD, Allen DA, Hicke L. The conserved Pkh-Ypk kinase cascade is required for endocytosis in yeast. The Journal of cell biology. 2002;156(2):241–8. Epub 2002/01/25. doi: 10.1083/jcb.200107135 [pii]. 11807089; PubMed Central PMCID: PMC2199229.
24. Kamada Y, Fujioka Y, Suzuki NN, Inagaki F, Wullschleger S, Loewith R, et al. Tor2 directly phosphorylates the AGC kinase Ypk2 to regulate actin polarization. Molecular and cellular biology. 2005;25(16):7239–48. doi: 10.1128/MCB.25.16.7239-7248.2005 16055732.
25. Aronova S, Wedaman K, Aronov PA, Fontes K, Ramos K, Hammock BD, et al. Regulation of ceramide biosynthesis by TOR complex 2. Cell metabolism. 2008;7(2):148–58. Epub 2008/02/06. doi: 10.1016/j.cmet.2007.11.015 S1550-4131(07)00372-5 [pii]. 18249174.
26. Berchtold D, Piccolis M, Chiaruttini N, Riezman I, Riezman H, Roux A, et al. Plasma membrane stress induces relocalization of Slm proteins and activation of TORC2 to promote sphingolipid synthesis. Nature cell biology. 2012;14(5):542–7. doi: 10.1038/ncb2480 22504275.
27. Niles BJ, Mogri H, Hill A, Vlahakis A, Powers T. Plasma membrane recruitment and activation of the AGC kinase Ypk1 is mediated by target of rapamycin complex 2 (TORC2) and its effector proteins Slm1 and Slm2. Proceedings of the National Academy of Sciences of the United States of America. 2012;109(5):1536–41. doi: 10.1073/pnas.1117563109 22307609; PubMed Central PMCID: PMC3277121.
28. Shimada K, Filipuzzi I, Stahl M, Helliwell SB, Studer C, Hoepfner D, et al. TORC2 Signaling Pathway Guarantees Genome Stability in the Face of DNA Strand Breaks. Molecular cell. 2013;51(6):829–39. Epub 2013/09/17. doi: 10.1016/j.molcel.2013.08.019 S1097-2765(13)00592-3 [pii]. 24035500.
29. Muir A, Ramachandran S, Roelants FM, Timmons G, Thorner J. TORC2-dependent protein kinase Ypk1 phosphorylates ceramide synthase to stimulate synthesis of complex sphingolipids. eLife. 2014;3. doi: 10.7554/eLife.03779 25279700; PubMed Central PMCID: PMC4217029.
30. Leskoske KL, Roelants FM, Martinez Marshall MN, Hill JM, Thorner J. The Stress-Sensing TORC2 Complex Activates Yeast AGC-Family Protein Kinase Ypk1 at Multiple Novel Sites. Genetics. 2017;207(1):179–95. doi: 10.1534/genetics.117.1124 28739659; PubMed Central PMCID: PMC5586371.
31. Roelants FM, Leskoske KL, Martinez Marshall MN, Locke MN, Thorner J. The TORC2-Dependent Signaling Network in the Yeast Saccharomyces cerevisiae. Biomolecules. 2017;7(3). doi: 10.3390/biom7030066 28872598; PubMed Central PMCID: PMC5618247.
32. Riggi M, Kusmider B, Loewith R. The flipside of the TOR coin—TORC2 and plasma membrane homeostasis at a glance. Journal of cell science. 2020;133(9). Epub 2020/05/13. doi: 10.1242/jcs.242040 32393676.
33. Matsuo T, Kubo Y, Watanabe Y, Yamamoto M. Schizosaccharomyces pombe AGC family kinase Gad8p forms a conserved signaling module with TOR and PDK1-like kinases. The EMBO journal. 2003;22(12):3073–83. Epub 2003/06/14. doi: 10.1093/emboj/cdg298 12805221; PubMed Central PMCID: PMC162150.
34. Weisman R, Choder M. The fission yeast TOR homolog, tor1+, is required for the response to starvation and other stresses via a conserved serine. The Journal of biological chemistry. 2001;276(10):7027–32. doi: 10.1074/jbc.M010446200 11096119
35. Kawai M, Nakashima A, Ueno M, Ushimaru T, Aiba K, Doi H, et al. Fission yeast tor1 functions in response to various stresses including nitrogen starvation, high osmolarity, and high temperature. Curr Genet. 2001;39(3):166–74. doi: 10.1007/s002940100198 11409178
36. Petersen J, Nurse P. TOR signalling regulates mitotic commitment through the stress MAP kinase pathway and the Polo and Cdc2 kinases. Nature cell biology. 2007;9(11):1263–72. doi: 10.1038/ncb1646 17952063.
37. Ikeda K, Morigasaki S, Tatebe H, Tamanoi F, Shiozaki K. Fission yeast TOR complex 2 activates the AGC-family Gad8 kinase essential for stress resistance and cell cycle control. Cell cycle. 2008;7(3):358–64. doi: 10.4161/cc.7.3.5245 18235227.
38. Laboucarie T, Detilleux D, Rodriguez-Mias RA, Faux C, Romeo Y, Franz-Wachtel M, et al. TORC1 and TORC2 converge to regulate the SAGA co-activator in response to nutrient availability. EMBO Rep. 2017. doi: 10.15252/embr.201744942 29079657.
39. Schonbrun M, Kolesnikov M, Kupiec M, Weisman R. TORC2 is required to maintain genome stability during S phase in fission yeast. The Journal of biological chemistry. 2013;288(27):19649–60. Epub 2013/05/25. doi: 10.1074/jbc.M113.464974 M113.464974 [pii]. 23703609; PubMed Central PMCID: PMC3707671.
40. Cohen A, Kupiec M, Weisman R. Glucose activates TORC2-Gad8 protein via positive regulation of the cAMP/cAMP-dependent protein kinase A (PKA) pathway and negative regulation of the Pmk1 protein-mitogen-activated protein kinase pathway. The Journal of biological chemistry. 2014;289(31):21727–37. doi: 10.1074/jbc.M114.573824 24928510; PubMed Central PMCID: PMC4118131.
41. Hatano T, Morigasaki S, Tatebe H, Ikeda K, Shiozaki K. Fission yeast Ryh1 GTPase activates TOR Complex 2 in response to glucose. Cell cycle. 2015;14(6):848–56. doi: 10.1080/15384101.2014.1000215 25590601.
42. Morigasaki S, Chin LC, Hatano T, Emori M, Iwamoto M, Tatebe H, et al. Modulation of TOR complex 2 signaling by the stress-activated MAPK pathway in fission yeast. Journal of cell science. 2019;132(19). doi: 10.1242/jcs.236133 31477575.
43. Martin R, Portantier M, Chica N, Nyquist-Andersen M, Mata J, Lopez-Aviles S. A PP2A-B55-Mediated Crosstalk between TORC1 and TORC2 Regulates the Differentiation Response in Fission Yeast. Current biology: CB. 2017;27(2):175–88. doi: 10.1016/j.cub.2016.11.037 28041796; PubMed Central PMCID: PMC5266790.
44. Oya E, Durand-Dubief M, Cohen A, Maksimov V, Schurra C, Nakayama JI, et al. Leo1 is essential for the dynamic regulation of heterochromatin and gene expression during cellular quiescence. Epigenetics & chromatin. 2019;12(1):45. doi: 10.1186/s13072-019-0292-7 31315658; PubMed Central PMCID: PMC6636030.
45. Pearce LR, Komander D, Alessi DR. The nuts and bolts of AGC protein kinases. Nat Rev Mol Cell Biol. 2010;11(1):9–22. Epub 2009/12/23. doi: 10.1038/nrm2822 20027184.
46. Arencibia JM, Pastor-Flores D, Bauer AF, Schulze JO, Biondi RM. AGC protein kinases: from structural mechanism of regulation to allosteric drug development for the treatment of human diseases. Biochim Biophys Acta. 2013;1834(7):1302–21. Epub 2013/03/26. doi: 10.1016/j.bbapap.2013.03.010 23524293.
47. Casamayor A, Torrance PD, Kobayashi T, Thorner J, Alessi DR. Functional counterparts of mammalian protein kinases PDK1 and SGK in budding yeast. Current biology: CB. 1999;9(4):186–97. Epub 1999/03/13. doi: 10.1016/s0960-9822(99)80088-8 10074427.
48. Niederberger C, Schweingruber ME. A Schizosaccharomyces pombe gene, ksg1, that shows structural homology to the human phosphoinositide-dependent protein kinase PDK1, is essential for growth, mating and sporulation. Molecular & general genetics: MGG. 1999;261(1):177–83. Epub 1999/03/10. doi: 10.1007/s004380050955 10071224.
49. Biondi RM, Cheung PC, Casamayor A, Deak M, Currie RA, Alessi DR. Identification of a pocket in the PDK1 kinase domain that interacts with PIF and the C-terminal residues of PKA. The EMBO journal. 2000;19(5):979–88. Epub 2000/03/04. doi: 10.1093/emboj/19.5.979 10698939; PubMed Central PMCID: PMC305637.
50. Biondi RM, Kieloch A, Currie RA, Deak M, Alessi DR. The PIF-binding pocket in PDK1 is essential for activation of S6K and SGK, but not PKB. The EMBO journal. 2001;20(16):4380–90. Epub 2001/08/14. doi: 10.1093/emboj/20.16.4380 11500365; PubMed Central PMCID: PMC125563.
51. Collins BJ, Deak M, Arthur JS, Armit LJ, Alessi DR. In vivo role of the PIF-binding docking site of PDK1 defined by knock-in mutation. The EMBO journal. 2003;22(16):4202–11. Epub 2003/08/13. doi: 10.1093/emboj/cdg407 12912918; PubMed Central PMCID: PMC175797.
52. Frodin M, Antal TL, Dummler BA, Jensen CJ, Deak M, Gammeltoft S, et al. A phosphoserine/threonine-binding pocket in AGC kinases and PDK1 mediates activation by hydrophobic motif phosphorylation. The EMBO journal. 2002;21(20):5396–407. Epub 2002/10/11. doi: 10.1093/emboj/cdf551 12374740; PubMed Central PMCID: PMC129083.
53. Yang J, Cron P, Thompson V, Good VM, Hess D, Hemmings BA, et al. Molecular mechanism for the regulation of protein kinase B/Akt by hydrophobic motif phosphorylation. Molecular cell. 2002;9(6):1227–40. Epub 2002/06/28. doi: 10.1016/s1097-2765(02)00550-6 12086620.
54. Schulze JO, Saladino G, Busschots K, Neimanis S, Suss E, Odadzic D, et al. Bidirectional Allosteric Communication between the ATP-Binding Site and the Regulatory PIF Pocket in PDK1 Protein Kinase. Cell Chem Biol. 2016;23(10):1193–205. Epub 2016/10/22. doi: 10.1016/j.chembiol.2016.06.017 27693059.
55. Pastor-Flores D, Schulze JO, Bahi A, Giacometti R, Ferrer-Dalmau J, Passeron S, et al. PIF-pocket as a target for C. albicans Pkh selective inhibitors. ACS Chem Biol. 2013;8(10):2283–92. Epub 2013/08/06. doi: 10.1021/cb400452z 23911092.
56. Schonbrun M, Laor D, Lopez-Maury L, Bahler J, Kupiec M, Weisman R. TOR complex 2 controls gene silencing, telomere length maintenance, and survival under DNA-damaging conditions. Molecular and cellular biology. 2009;29(16):4584–94. Epub 2009/06/24. doi: 10.1128/MCB.01879-08 MCB.01879-08 [pii]. 19546237; PubMed Central PMCID: PMC2725747.
57. Maundrell K. Thiamine-repressible expression vectors pREP and pRIP for fission yeast. Gene. 1993;123(1):127–30. doi: 10.1016/0378-1119(93)90551-d 8422996
58. Ikai N, Nakazawa N, Hayashi T, Yanagida M. The reverse, but coordinated, roles of Tor2 (TORC1) and Tor1 (TORC2) kinases for growth, cell cycle and separase-mediated mitosis in Schizosaccharomyces pombe. Open biology. 2011;1(3):110007. Epub 2012/05/31. doi: 10.1098/rsob.110007 [pii]. 22645648.
59. Laor D, Cohen A, Kupiec M, Weisman R. TORC1 Regulates Developmental Responses to Nitrogen Stress via Regulation of the GATA Transcription Factor Gaf1. MBio. 2015;6(4). doi: 10.1128/mBio.00959-15 26152587; PubMed Central PMCID: PMC4488950.
60. Madrid M, Vazquez-Marin B, Franco A, Soto T, Vicente-Soler J, Gacto M, et al. Multiple crosstalk between TOR and the cell integrity MAPK signaling pathway in fission yeast. Scientific reports. 2016;6:37515. doi: 10.1038/srep37515 27876895; PubMed Central PMCID: PMC5120329.
61. Carr AM. DNA structure dependent checkpoints as regulators of DNA repair. DNA Repair (Amst). 2002;1(12):983–94. doi: 10.1016/s1568-7864(02)00165-9 12531008.
62. Dutta C, Patel PK, Rosebrock A, Oliva A, Leatherwood J, Rhind N. The DNA replication checkpoint directly regulates MBF-dependent G1/S transcription. Molecular and cellular biology. 2008;28(19):5977–85. doi: 10.1128/MCB.00596-08 18662996; PubMed Central PMCID: PMC2547018.
63. Cohen A, Kupiec M, Weisman R. Gad8 Protein Is Found in the Nucleus Where It Interacts with the MluI Cell Cycle Box-binding Factor (MBF) Transcriptional Complex to Regulate the Response to DNA Replication Stress. The Journal of biological chemistry. 2016;291(17):9371–81. doi: 10.1074/jbc.M115.705251 26912660; PubMed Central PMCID: PMC4861499.
64. Wan S, Capasso H, Walworth NC. The topoisomerase I poison camptothecin generates a Chk1-dependent DNA damage checkpoint signal in fission yeast. Yeast. 1999;15(10A):821–8. doi: 10.1002/(SICI)1097-0061(199907)15:10A<821::AID-YEA422>3.0.CO;2-# 10407262.
65. Maiyar AC, Leong ML, Firestone GL. Importin-alpha mediates the regulated nuclear targeting of serum- and glucocorticoid-inducible protein kinase (Sgk) by recognition of a nuclear localization signal in the kinase central domain. Molecular biology of the cell. 2003;14(3):1221–39. Epub 2003/03/13. doi: 10.1091/mbc.e02-03-0170 12631736; PubMed Central PMCID: PMC151592.
66. Moreno S, Klar A, Nurse P. Molecular genetic analysis of fission yeast Schizosaccharomyces pombe. Methods Enzymol. 1991;194:795–823. doi: 10.1016/0076-6879(91)94059-l 2005825.
67. Baker K, Kirkham S, Halova L, Atkin J, Franz-Wachtel M, Cobley D, et al. TOR complex 2 localises to the cytokinetic actomyosin ring and controls the fidelity of cytokinesis. Journal of cell science. 2016;129(13):2613–24. doi: 10.1242/jcs.190124 27206859; PubMed Central PMCID: PMC4958305.
68. UniProt Consortium T. UniProt: the universal protein knowledgebase. Nucleic acids research. 2018;46(5):2699–. doi: 10.1093/nar/gky092 29425356
69. Altschul SF, Gish W, Miller W, Myers EW, Lipman DJ. Basic local alignment search tool. Journal of molecular biology. 1990;215(3):403–10. Epub 1990/10/05. doi: 10.1016/S0022-2836(05)80360-2 2231712.
70. Zhao B, Lehr R, Smallwood AM, Ho TF, Maley K, Randall T, et al. Crystal structure of the kinase domain of serum and glucocorticoid-regulated kinase 1 in complex with AMP PNP. Protein Sci. 2007;16(12):2761–9. Epub 10/26. doi: 10.1110/ps.073161707 17965184.
71. Chu N, Salguero AL, Liu AZ, Chen Z, Dempsey DR, Ficarro SB, et al. Akt Kinase Activation Mechanisms Revealed Using Protein Semisynthesis. Cell. 2018;174(4):897–907 e14. Epub 2018/08/07. doi: 10.1016/j.cell.2018.07.003 30078705; PubMed Central PMCID: PMC6139374.
72. Thompson JD, Higgins DG, Gibson TJ. CLUSTAL W: improving the sensitivity of progressive multiple sequence alignment through sequence weighting, position-specific gap penalties and weight matrix choice. Nucleic acids research. 1994;22(22):4673–80. doi: 10.1093/nar/22.22.4673 7984417.
73. Sali A, Blundell TL. Comparative protein modelling by satisfaction of spatial restraints. Journal of molecular biology. 1993;234(3):779–815. Epub 1993/12/05. doi: 10.1006/jmbi.1993.1626 8254673.
74. Laskowski RA, MacArthur MW, Moss DS, Thornton JM. PROCHECK: a program to check the stereochemical quality of protein structures. Journal of Applied Crystallography. 1993;26(2):283–91. doi: 10.1107/S0021889892009944
75. Van Der Spoel D, Lindahl E, Hess B, Groenhof G, Mark AE, Berendsen HJC. GROMACS: Fast, flexible, and free. Journal of Computational Chemistry. 2005;26(16):1701–18. doi: 10.1002/jcc.20291 16211538
76. Maier JA, Martinez C, Kasavajhala K, Wickstrom L, Hauser KE, Simmerling C. ff14SB: Improving the Accuracy of Protein Side Chain and Backbone Parameters from ff99SB. Journal of Chemical Theory and Computation. 2015;11(8):3696–713. doi: 10.1021/acs.jctc.5b00255 26574453
77. Wang J, Wang W, Kollman PA, Case DA. Automatic atom type and bond type perception in molecular mechanical calculations. Journal of molecular graphics & modelling. 2006;25(2):247–60. Epub 2006/02/07. doi: 10.1016/j.jmgm.2005.12.005 16458552.
78. Bochevarov AD, Harder E, Hughes TF, Greenwood JR, Braden DA, Philipp DM, et al. Jaguar: A high-performance quantum chemistry software program with strengths in life and materials sciences. International Journal of Quantum Chemistry. 2013;113(18):2110–42. doi: 10.1002/qua.24481
79. Darden T, York D, Pedersen L. Particle mesh Ewald: An N·log(N) method for Ewald sums in large systems. Journal of Chemical Physics. 1993;98:10089.
80. Humphrey W, Dalke A, Schulten K. VMD: Visual molecular dynamics. Journal of Molecular Graphics. 1996;14(1):33–8. doi: 10.1016/0263-7855(96)00018-5 8744570
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