Structural basis for exploring the allosteric inhibition of human kidney type glutaminase

Oncotarget

Volumn 7, Issue 36, 2016, Pages 57943-57954

  Ramachandran, Sarath ^a   Pan, Catherine Qiurong ^b   Zimmermann, Sarah C ^c   Duvall, Bridget ^c   Tsukamoto, Takashi ^c   Low, Boon Chuan ^a,b   Sivaraman, J ^a  

^a NATIONAL UNIVERSITY OF SINGAPORE   (Singapore)

^b NATIONAL UNIVERSITY OF SINGAPORE   (Singapore)

^c JOHNS HOPKINS UNIVERSITY SCHOOL OF MEDICINE   (United States)

Author keywords

Allosteric inhibitors; BPTES; Cancer target; CB 839; Glutaminase

Indexed keywords

ANTINEOPLASTIC AGENT; BIS 2 (5 PHENYLACETAMIDO 1,3,4 THIADIAZOL 2 YL)ETHYL SULFIDE; CB 839; ENZYME INHIBITOR; GLUTAMINASE; KIDNEY TYPE GLUTAMINASE; N,N' [5,5' (CYCLOHEXANE 1,3 DIYL)BIS(1,3,4 TIADIAZOLE 5,2 DIYL)]BIS(2 PHENYLACETAMIDE); UNCLASSIFIED DRUG; BIS-2-(5-PHENYLACETAMIDO-1,2,4-THIADIAZOL-2-YL)ETHYL SULFIDE; PROTEIN BINDING; SULFIDE; THIADIAZOLE DERIVATIVE;

ALLOSTERISM; ARTICLE; BINDING AFFINITY; COMPLEX FORMATION; CONCENTRATION RESPONSE; CONTROLLED STUDY; CRYSTAL STRUCTURE; DRUG MECHANISM; DRUG PROTEIN BINDING; DRUG STRUCTURE; EMBRYO; ENZYME INHIBITION; HUMAN; HUMAN CELL; IC50; STRUCTURE ANALYSIS; ALLOSTERIC SITE; ANTAGONISTS AND INHIBITORS; CELL PROLIFERATION; CHEMISTRY; CONFORMATION; ENZYMOLOGY; HEK293 CELL LINE; KIDNEY; KIDNEY TUMOR; PROTEIN CONFORMATION;

ALLOSTERIC SITE; ANTINEOPLASTIC AGENTS; CELL PROLIFERATION; GLUTAMINASE; HEK293 CELLS; HUMANS; INHIBITORY CONCENTRATION 50; KIDNEY; KIDNEY NEOPLASMS; MOLECULAR CONFORMATION; PROTEIN BINDING; PROTEIN CONFORMATION; SULFIDES; THIADIAZOLES;

EID: 84988373695     PISSN: None     EISSN: 19492553     Source Type: Journal    
DOI: 10.18632/oncotarget.10791     Document Type: Article

References (50)

1. Vander Heiden MG, Cantley LC and Thompson CB. Understanding the Warburg effect: the metabolic requirements of cell proliferation. Science. 2009; 324:1029-1033.
2. Warburg O. On the origin of cancer cells. Science. 1956; 123:309-314.
3. DeBerardinis RJ, Lum JJ, Hatzivassiliou G and Thompson CB. The Biology of Cancer: Metabolic Reprogramming Fuels Cell Growth and Proliferation. Cell Metabolism. 2008; 7:11-20.
4. Aledo JC, Gomez-Fabre PM, Olalla L and Marquez J. Identification of two human glutaminase loci and tissuespecific expression of the two related genes. Mamm Genome. 2000; 11:1107-1110.
5. Wise DR, DeBerardinis RJ, Mancuso A, Sayed N, Zhang XY, Pfeiffer HK, Nissim I, Daikhin E, Yudkoff M, McMahon SB and Thompson CB. Myc regulates a transcriptional program that stimulates mitochondrial glutaminolysis and leads to glutamine addiction. Proceedings of the National Academy of Sciences. 2008; 105:18782-18787.
6. Gao P, Tchernyshyov I, Chang T-C, Lee Y-S, Kita K, Ochi T, Zeller KI, De Marzo AM, Van Eyk JE, Mendell JT and Dang CV. c-Myc suppression of miR-23a/b enhances mitochondrial glutaminase expression and glutamine metabolism. Nature. 2009; 458:762-765.
7. Wang J-B, Erickson JW, Fuji R, Ramachandran S, Gao P, Dinavahi R, Wilson KF, Ambrosio ALB, Dias SMG, Dang CV and Cerione RA. Targeting Mitochondrial Glutaminase Activity Inhibits Oncogenic Transformation. Cancer Cell. 2010; 18:207-219.
8. Thangavelu K, Pan CQ, Karlberg T, Balaji G, Uttamchandani M, Suresh V, Schuler H, Low BC and Sivaraman J. Structural basis for the allosteric inhibitory mechanism of human kidney-type glutaminase (KGA) and its regulation by Raf-Mek-Erk signaling in cancer cell metabolism. Proc Natl Acad Sci U S A. 2012; 109:7705-7710.
9. Son J, Lyssiotis CA, Ying H, Wang X, Hua S, Ligorio M, Perera RM, Ferrone CR, Mullarky E, Shyh-Chang N, Kang Y, Fleming JB, Bardeesy N, Asara JM, Haigis MC, DePinho RA, et al. Glutamine supports pancreatic cancer growth through a KRAS-regulated metabolic pathway. Nature. 2013; 496:101-105.
10. Seltzer MJ, Bennett BD, Joshi AD, Gao P, Thomas AG, Ferraris DV, Tsukamoto T, Rojas CJ, Slusher BS, Rabinowitz JD, Dang CV and Riggins GJ. Inhibition of glutaminase preferentially slows growth of glioma cells with mutant IDH1. Cancer Res. 2010; 70:8981-8987.
11. van den Heuvel AP, Jing J, Wooster RF and Bachman KE. Analysis of glutamine dependency in non-small cell lung cancer: GLS1 splice variant GAC is essential for cancer cell growth. Cancer Biol Ther. 2012; 13:1185-1194.
12. Lora J, Alonso FJ, Segura JA, Lobo C, Marquez J and Mates JM. Antisense glutaminase inhibition decreases glutathione antioxidant capacity and increases apoptosis in Ehrlich ascitic tumour cells. Eur J Biochem. 2004; 271:4298-4306.
13. Thangavelu K, Chong QY, Low BC and Sivaraman J. Structural Basis for the Active Site Inhibition Mechanism of Human Kidney-Type Glutaminase (KGA). Scientific Reports. 2014; 4.
14. Catane R, Von Hoff DD, Glaubiger DL and Muggia FM. Azaserine, DON, and azotomycin: three diazo analogs of L-glutamine with clinical antitumor activity. Cancer Treat Rep. 1979; 63:1033-1038.
15. Kisner DL, Catane R and Muggia FM. The rediscovery of DON (6-diazo-5-oxo-L-norleucine). Recent Results Cancer Res. 1980; 74:258-263.
16. Katt WP, Ramachandran S, Erickson JW and Cerione RA. Dibenzophenanthridines as inhibitors of glutaminase C and cancer cell proliferation. Mol Cancer Ther. 2012; 11:1269-1278.
17. Robinson MM, McBryant SJ, Tsukamoto T, Rojas C, Ferraris DV, Hamilton SK, Hansen JC and Curthoys NP. Novel mechanism of inhibition of rat kidney-type glutaminase by bis-2-(5-phenylacetamido-1,2,4-thiadiazol-2-yl)ethyl sulfide (BPTES). Biochem J. 2007; 406:407-414.
18. Qie S, Chu C, Li W, Wang C and Sang N. ErbB2 activation upregulates glutaminase 1 expression which promotes breast cancer cell proliferation. J Cell Biochem. 2014; 115:498-509.
19. Le A, Lane AN, Hamaker M, Bose S, Gouw A, Barbi J, Tsukamoto T, Rojas CJ, Slusher BS, Zhang H, Zimmerman LJ, Liebler DC, Slebos RJ, Lorkiewicz PK, Higashi RM, Fan TW, et al. Glucose-independent glutamine metabolism via TCA cycling for proliferation and survival in B cells. Cell Metab. 2012; 15:110-121.
20. Shanware NP, Bray K, Eng CH, Wang F, Follettie M, Myers J, Fantin VR and Abraham RT. Glutamine deprivation stimulates mTOR-JNK-dependent chemokine secretion. Nat Commun. 2014; 5:4900.
21. DeLaBarre B, Gross S, Fang C, Gao Y, Jha A, Jiang F, Song JJ, Wei W and Hurov JB. Full-length human glutaminase in complex with an allosteric inhibitor. Biochemistry. 2011; 50:10764-10770.
22. Shukla K, Ferraris DV, Thomas AG, Stathis M, Duvall B, Delahanty G, Alt J, Rais R, Rojas C, Gao P, Xiang Y, Dang CV, Slusher BS and Tsukamoto T. Design, synthesis, and pharmacological evaluation of bis-2-(5-phenylacetamido-1,2,4-thiadiazol-2-yl)ethyl sulfide 3 (BPTES) analogs as glutaminase inhibitors. J Med Chem. 2012; 55:10551-10563.
23. Gross MI, Demo SD, Dennison JB, Chen L, Chernov-Rogan T, Goyal B, Janes JR, Laidig GJ, Lewis ER, Li J, MacKinnon AL, Parlati F, Rodriguez MLM, Shwonek PJ, Sjogren EB, Stanton TF, et al. Antitumor Activity of the Glutaminase Inhibitor CB-839 in Triple-Negative Breast Cancer. Molecular Cancer Therapeutics. 2014; 13:890-901.
24. Matre P, Shariati M, Velez J, Qi Y, Konoplev S, Su XP, DiNardo CD, Daver N, Majeti R, Andreeff M, Chan SM and Konopleva M. Efficacy of Novel Glutaminase Inhibitor CB-839 in Acute Myeloid Leukemia. Blood. 2014; 124.
25. Sharma D, Ravillah D, Ray A, Song Y, Munshi NC, Richardson PG, Chauhan D and Anderson KC. Anti-Myeloma Activity of a Novel Glutaminase Inhibitor CB-839. Blood. 2014; 124.
26. Parlati F, Bromley-Dulfano S, Demo S, Janes J, Gross M, Lewis E, MacKinnon A, Rodriguez M, Yang JF, Zhao F and Bennett M. Antitumor Activity Of The Glutaminase Inhibitor CB-839 In Hematological Malignances. Blood. 2013; 122.
27. Lemieux RM, Popovici-Muller J, Salituro FG, Saunders JO, Travins J and Chen Y. (2014). Compounds and their methods of use. United States Patent US20140142081 A1.
28. Veber DF, Johnson SR, Cheng HY, Smith BR, Ward KW and Kopple KD. Molecular properties that influence the oral bioavailability of drug candidates. J Med Chem. 2002; 45:2615-2623.
29. Leroux FR, Manteau B, Vors J-P and Pazenok S. Trifluoromethyl ethers-synthesis and properties of an unusual substituent. Beilstein journal of organic chemistry. 2008; 4:13.
30. Nenajdenko V. (2014). Fluorine in Heterocyclic Chemistry: Springer.
31. Krissinel E and Henrick K. Inference of macromolecular assemblies from crystalline state. J Mol Biol. 2007; 372:774-797.
32. Grassian AR, Parker SJ, Davidson SM, Divakaruni AS, Green CR, Zhang X, Slocum KL, Pu M, Lin F, Vickers C, Joud-Caldwell C, Chung F, Yin H, Handly ED, Straub C, Growney JD, et al. IDH1 mutations alter citric acid cycle metabolism and increase dependence on oxidative mitochondrial metabolism. Cancer Res. 2014; 74:3317-3331.
33. Christofk HR, Vander Heiden MG, Harris MH, Ramanathan A, Gerszten RE, Wei R, Fleming MD, Schreiber SL and Cantley LC. The M2 splice isoform of pyruvate kinase is important for cancer metabolism and tumour growth. Nature. 2008; 452:230-233.
34. Muller FL, Colla S, Aquilanti E, Manzo VE, Genovese G, Lee J, Eisenson D, Narurkar R, Deng P, Nezi L, Lee MA, Hu B, Hu J, Sahin E, Ong D, Fletcher-Sananikone E, et al. Passenger deletions generate therapeutic vulnerabilities in cancer. Nature. 2012; 488:337-342.
35. Hensley CT, Wasti AT and DeBerardinis RJ. Glutamine and cancer: cell biology, physiology, and clinical opportunities. J Clin Invest. 2013; 123:3678-3684.
36. Herranz D, Ambesi-Impiombato A, Sudderth J, Sanchez-Martin M, Belver L, Tosello V, Xu L, Wendorff AA, Castillo M, Haydu JE, Marquez J, Mates JM, Kung AL, Rayport S, Cordon-Cardo C, DeBerardinis RJ, et al. Metabolic reprogramming induces resistance to anti-NOTCH1 therapies in T cell acute lymphoblastic leukemia. Nat Med. 2015; 21:1182-1189.
37. Chakrabarti G, Moore ZR, Luo X, Ilcheva M, Ali A, Padanad M, Zhou Y, Xie Y, Burma S, Scaglioni PP, Cantley LC, DeBerardinis RJ, Kimmelman AC, Lyssiotis CA and Boothman DA. Targeting glutamine metabolism sensitizes pancreatic cancer to PARP-driven metabolic catastrophe induced by ss-lapachone. Cancer Metab. 2015; 3:12.
38. Jacque N, Ronchetti AM, Larrue C, Meunier G, Birsen R, Willems L, Saland E, Decroocq J, Trovati Maciel T, Lambert M, Poulain L, Hospital MA, Sujobert P, Joseph L, Chapuis N, Lacombe C, et al. Targeting glutaminolysis has anti-leukemic activity in acute myeloid leukemia and synergizes with BCL-2 inhibition. Blood. 2015.
39. Zimmermann SC, Wolf EF, Luu A, Thomas AG, Stathis M, Poore B, Nguyen C, Le A, Rojas C, Slusher BS and Tsukamoto T. Allosteric Glutaminase Inhibitors Based on a 1,4-Di(5-amino-1,3,4-thiadiazol-2-yl)butane Scaffold. ACS Med Chem Lett. 2016; 7:520-524.
40. Li J, Chen L, Goyal B, Laidig G, Stanton TF and Sjogren EB. 2013. Heterocyclic inhibitors of glutaminase. United States Patent US8604016.
41. McDermott LA, Iyer P, Vernetti L, Rimer S, Sun J, Boby M, Yang T, Fioravanti M, O'Neill J, Wang L, Drakes D, Katt W, Huang Q and Cerione R. Design and evaluation of novel glutaminase inhibitors. Bioorg Med Chem. 2016; 24:1819-1839.
42. Kenny J, Bao Y, Hamm B, Taylor L, Toth A, Wagers B and Curthoys NP. Bacterial expression, purification, and characterization of rat kidney-type mitochondrial glutaminase. Protein Expr Purif. 2003; 31:140-148.
43. Minor W and Otwinowski Z. HKL2000 (Denzo-SMN) Software Package. Processing of X-ray Diffraction Data Collected in Oscillation Mode. Methods in Enzymology, Macromolecular Crystallography, Academic Press, New York. 1997.
44. McCoy AJ, Grosse-Kunstleve RW, Adams PD, Winn MD, Storoni LC and Read RJ. Phaser crystallographic software. J Appl Crystallogr. 2007; 40:658-674.
45. Moriarty NW, Grosse-Kunstleve RW and Adams PD. electronic Ligand Builder and Optimization Workbench (eLBOW): a tool for ligand coordinate and restraint generation. Acta Crystallogr D Biol Crystallogr. 2009; 65:1074-1080.
46. Emsley P and Cowtan K. Coot: model-building tools for molecular graphics. Acta Crystallogr D Biol Crystallogr. 2004; 60:2126-2132.
47. Afonine PV, Grosse-Kunstleve RW, Echols N, Headd JJ, Moriarty NW, Mustyakimov M, Terwilliger TC, Urzhumtsev A, Zwart PH and Adams PD. Towards automated crystallographic structure refinement with phenix.refine. Acta Crystallogr D Biol Crystallogr. 2012; 68:352-367.
48. Ferreira AP, Cassago A, Goncalves Kde A, Dias MM, Adamoski D, Ascencao CF, Honorato RV, de Oliveira JF, Ferreira IM, Fornezari C, Bettini J, Oliveira PS, Paes Leme AF, Portugal RV, Ambrosio AL and Dias SM. Active glutaminase C self-assembles into a supratetrameric oligomer that can be disrupted by an allosteric inhibitor. J Biol Chem. 2013; 288:28009-28020.
49. Laskowski RA, Macarthur MW, Moss DS and Thornton JM. Procheck-a Program to Check the Stereochemical Quality of Protein Structures. Journal of Applied Crystallography. 1993; 26:283-291.
50. DeLano WL. The PyMOL molecular graphics system. 2002.