Inhibitors of the Cdc34 acidic loop: A computational investigation integrating molecular dynamics, virtual screening and docking approaches

FEBS Open Bio

Volumn 4, Issue , 2014, Pages 473-484

  Arrigoni, Alberto ^a   Bertini, Luca ^a   De Gioia, Luca ^a   Papaleo, Elena ^a  

^a UNIVERSITY OF MILANO BICOCCA   (Italy)

Author keywords

Cdc34; Docking; E2 conjugating enzyme; Ubiquitin; Ubiquitination; Virtual screening

Indexed keywords

HYDROGEN; PHOSPHATASE; PROTEIN CDC34; UBIQUITIN; UNCLASSIFIED DRUG; 1 (5 BENZYL 2H 1,2,4 (TRIAZOL 3 YL) 3 (1,4,5,6 TETRAHYDROCYCLOPENTA[D]PYRAZOL 3 YLMETHYL)UREA; 1 (5 METHYLISOXAZOL 3 YL) 3 [1 [4 (1,2,4 TRIAZOL 1 YL)PHENYL]ETHYL]UREA; 2 (4 CYANOPHENOXY) N (4 METHYL 2 OXO CHROMEN 7 YL)ACETAMIDE; 2 BENZYL 2,3,4,6 TETRAHYDRO 1H[1,3,5]TRIAZINO[1',2':3,4][1,3,5]TRIAZINO[1,2 A]BENZIMIDAZOLE; 3 (6,7 DIHYDRO 5H PYRROLO[1,2 D][1,2,4]TRIAZOL 3 YLMETHYL) 1 (5 ISOBUTYL 4H 1,2,4 TRIAZOL 3 YL)UREA; 3 PHENYL 5 [[4 (TETRAZOL 1 YL)PHENOXY]METHYL]ISOXAZOLE; 4 CYANO N [5 (4 METHOXYPHENYL) 4H 1,2,4 TRIAZOL 3 YL]BENZAMIDE; 4 CYANO N [5 (4 TOLYL) 4H 1,2,4 TRIAZOL 3 YL]BENZAMIDE; 4 [(6 METHYLIMIDAZO[1,2 A]PYRIDIN 2 YL)METHOXY] N (4H 1,2,4 TRIAZOL 3 YL)BENZAMIDE; 4 [(8 METHYLIMIDAZO[1,2 A]PYRIDIN 2 YL)METHOXY] N (4H 1,2,4 TRIAZOL 3 YL)BENZAMIDE; 4,6 DIMETHYL N [3 (5 PHENYL 1H PYRAZOL 3 YL) 1H 1,2,4 TRIAZOL 5 YL]PYRIMIDIN 2 AMINE; 5 METHYL N [2 [3 (3 PYRIDINYL) 1H 1,2,4 TRIAZOL 5 YL]ETHYL] 2 INDOLINECARBOXAMIDE; 6 IMIDAZOL 1 YL N [3 (5 METHYLTETRAZOL 1 YL)PHENYL]PYRIDINE 3 CARBOXAMIDE; CDC34 UBIQUITIN; CELL CYCLE PROTEIN; LIGASE INHIBITOR; N (1H 1,2,4 TRIAZOL 3 YL)[[2 METHYL 5 [[N (1H 1,2,4 TRIAZOL 3 YL)CARBAMOYL]AMINO]PHENYL]AMINO]CARBOXAMIDE; N (1H BENZIMIDAZOL 2 YL) 4 UREIDO BENZAMIDE; N (1H BENZIMIDAZOL 2 YL) 5 (CYCLOPROPANECARBONYLAMINO)THIOPHENE 2 CARBOXAMIDE; N (1H BENZIMIDAZOL 2 YL) 5 PHENYL 1H PYRAZOLE 3 CARBOXAMIDE; N (2 OXO 3,4 DIHYDRO 1H QUINOLIN 6 YL) 5 PHENYL 1H PYRAZOLE 3 CARBOXAMIDE; N (2,3 DIHYDRO 1H INDEN 2 YL) 5 [3 (METHOXYMETHYL) 1,2,4 OXADIAZOL 5 YL] 2 PYRIDINAMINE; N (4 CHLOROPHENYL) 4 OXO 1,2,3,4 TETRAHYDROPYRIMIDO[1,2 A]BENZIMIDAZOLE 2 CARBOXAMIDE; N [4 (1H BENZOIMIDAZOL 2 YLCARBAMOYL)PHENYL]FURAN 2 CARBOXAMIDE; N [4 METHYL 3 (TETRAZOL 1 YL)PHENYL] 4 (12,4 TRIAZOL 1 YL)BENZAMIDE; N [4 METHYL 3 (TETRAZOL 1 YL)PHENYL] 4 PYRAZOL 1 YL BENZAMIDE; N [5 (4 FLUOROPHENYL) 4H 1,2,4 TRIAZOL 3 YL] 4 METHOXY BENZAMIDE; UBIQUITIN CONJUGATING ENZYME E2; UNINDEXED DRUG; [4 (2 PYRIDYLMETHYL)PIPERAZIN 1 YL] [4 (1,2,4 TRIAZOL 1 YL)PHENYL]METHANONE;

ARTICLE; BINDING SITE; HYDROGEN BOND; MOLECULAR DOCKING; MOLECULAR DYNAMICS; PHARMACOPHORE; PRIORITY JOURNAL; PROTEIN CONFORMATION; SCREENING; STATIC ELECTRICITY; UBIQUITINATION; VIRTUAL SCREENING; DRUG SCREENING; ENZYME ACTIVE SITE; ENZYME ACTIVITY; ENZYME CONFORMATION; ENZYME INHIBITION;

EID: 84901978817     PISSN: 22115463     EISSN: None     Source Type: Journal    
DOI: 10.1016/j.fob.2014.04.011     Document Type: Article

References (33)

1. Spasser L., Brik A. Chemistry and biology of the ubiquitin signal. Angew. Chem. Int. Ed. Engl. 2012, 51:6840-6862.
2. Nagy V., Dikic I. Ubiquitin ligase complexes: from substrate selectivity to conjugational specificity. Biol. Chem. 2010, 391:163-169.
3. Harper J.W., Schulman B.A. Structural complexity in ubiquitin recognition. Cell 2006, 124(2006):1133-1136.
4. Komander D., Rape M. The ubiquitin code. Annu. Rev. Biochem. 2012, 81:203-229.
5. Komander D. The emerging complexity of protein ubiquitination. Biochem. Soc. Trans. 2009, 37:937-953.
6. Sadowski M., Suryadinata R., Tan A.R., Roesley S.N.A., Sarcevic B. Protein monoubiquitination and polyubiquitination generate structural diversity to control distinct biological processes. IUBMB Life 2012, 64:136-142.
7. Trempe J.F. Reading the ubiquitin postal code. Curr. Opin. Struct. Biol. 2011, 21:792-801.
8. Liu J., Nussinov R. The role of allostery in the ubiquitin-proteasome system. Crit. Rev. Biochem. Mol. Biol. 2013, 48:89-97.
9. Ye Y., Rape M. Building ubiquitin chains: E2 enzymes at work. Nat. Rev. Mol. Cell Biol. 2013, 10:755-764.
10. Wenzel D.M., Stoll K.E., Klevit R.E. E2s: structurally economical and functionally replete. Biochem. J. 2011, 433:31-42.
11. Van WijK S.J., Timmers H.T. The family of ubiquitin-conjugating enzymes (E2s): deciding between life and death of proteins. FASEB J. 2010, 24:981-993.
12. Michelle C., Vourc'h P., Mignon L., Andres C.R. What was the set of ubiquitin and ubiquitin-like conjugating enzymes in the eukaryote common ancestor?. J. Mol. Evol. 2009, 68:616-628.
13. Papaleo E., Ranzani V., Tripodi F., Vitriolo A., Cirulli C., Fantucci P., Alberghina L., Vanoni M., De Gioia L., Coccetti P. An acidic loop and cognate phosphorylation sites define a molecular switch that modulates ubiquitin charging activity in Cdc34-like enzymes. PLoS Comput. Biol. 2011, 7:e1002056.
14. Tanaka K., Kondoh N., Shuda M., Matsubara O., Imazeki N., Ryo A., Wakatsuki T., Hada A., Goseki N., Igari T., Hatsuse K., Aihara T., Horiuchi S., Yamamoto N., Yamamoto M. Enhanced expression of mRNAs of antisecretory factor-1, gp96, DAD1 and CDC34 in human hepatocellular carcinomas. Biochim. Biophys. Acta 2011, 1536:1-12.
15. Eliseeva E., Pati D., Diccinanni M.B., Yu A.L., Mohsin S.K., Margolin J.F., Plon S.E. Expression and localization of the CDC34 ubiquitin-conjugating enzymes in pediatric acute lymphoblastic leukemia. Cell Growth Differ. 2001, 12:427-433.
16. Zhang Z., Wang Y., Yao R., Li J., Yan Y., La Regina M., Lemon W.L., Grubbs C.J., Lubet R.A., You M. Cancer chemopreventive activity of a mixture of Chinese herbs (antitumor B) in mouse lung tumor models. Oncogene 2004, 23:3841-3850.
17. Chauhan D., Li G., Hideshima T., Podar K., Shringarpure R., Mitsiades C., Munshi N., Yew P.R., Anderson K.C. Blockade of ubiquitin-conjugating enzyme CDC34 enhances anti-myeloma activity of Bortezomib/Proteasome inhibitor PS-341. Oncogene 2004, 23:3597-35602.
18. Price G.R., Armes J.E., Ramus S.J., Provenzano E., Kumar B., Cowie T.F., Ciciulla J., Hutchins A.M., Thomas M., Venter D.J. Phenotype-directed analysis of genotype in early-onset, familiar breast cancers. Pathology 2006, 38:520-527.
19. Zeng Y., Abdallah A., Lu J.P., Wang T., Chen Y.H., Terrian D.M., Kim K., Lu Q. Delta-Catenin promotes prostate cancer cell growth and progression by altering cell cycle and survival gene profiles. Mol. Cancer 2009, 8:19.
20. Ceccarelli D.F., Tang X., Pelletier B., Orlicky S., Xie W., Plantevin V., Neculai D., Chou Y.C., Ogunjimi A., Al-Hakim A., Varelas X., Koszela J., Wasney G.A., Vedadi M., Dhe-Paganon S., Cox S., Xu S., Lopez-Girona A., Mercurio F., Wrana J., Durocher D., Meloche S., Webb D.R., Tyers M., Sicheri F. An allosteric inhibitor of the human Cdc34 ubiquitin-conjugating enzyme. Cell 2011, 145:1075-1087.
21. Huang H., Ceccarelli D.F., Orlicky S., St-Cyr D.J., Ziemba A., Garg P., Plamondon S., Auer M., Sidhu S., Marinier A., Kleiger G., Tyers M., Sicheri F. E2 enzyme inhibition by stabilization of a low-affinity interface with ubiquitin. Nat. Chem. Biol. 2014, 10:156-163.
22. Sanders M.A., Brahemi G., Nangia-Makker P., Balan V., Morelli M., Kothayer H., Westwell A.D., Shekhar M.P. Novel inhibitors of Rad6 ubiquitin conjugating enzyme: design, synthesis, identification and functional characterization. Mol. Cancer Ther. 2013, 12:373-383.
23. Papaleo E., Casiraghi N., Arrigoni A., Vanoni M., Coccetti P., De Gioia L. Loop 7 of E2 enzymes: an ancestral conserved functional motif involved in the E2-mediated steps of the ubiquitination cascade. PLoS ONE 2012, 7:e40786.
24. Irwin J.J., Sterling T., Mysinger M.M., Bolstad E.S., Coleman R.G. ZINC: a free tool to discover chemistry for biology. J. Chem. Inf. Model. 2012, 52:1757-1768.
25. Irwin J.J., Shoichet B.K., Mysinger M.M., Huang N., Colizzi F., Wassam P., Cao Y. Automated docking screens: a feasibility study. J. Med. Chem. 2009, 52:5712-5720.
26. Morris G.M., Huey R., Lindstrom W., Sanner M.F., Belew R.K., Goodsell D.S., Olson A.J. AutoDock4 and AutoDockTools4: automated docking with selective receptor flexibility. J. Comput. Chem. 2009, 30:2785-2791.
27. Lipinski C.A. Lead- and drug-like compounds: the rule of five revolution. Drug Discov. Today Technol. 2004, 1:337-341.
28. Sadowski M., Suryadinata R., Lai X., Heierhorst J., Sarcevic B. Molecular basis for lysine specificity in the yeast ubiquitin-conjugating enzyme Cdc34. Mol. Cell. Biol. 2010, 30:2316-2329.
29. Yunus A.A., Lima C.D. Lysine activation and functional analysis of E2-mediated conjugation in the SUMO pathway. Nat. Struct. Mol. Biol. 2006, 13:491-499.
30. Coccetti P., Tripodi F., Tedeschi G., Nonnis S., Marin O., Fantinato S., Cirulli C., Vanoni M., Alberghina L. The CK2 phosphorylation of catalytic domain of Cdc34 modulates its activity at the G1 to S transition in Saccharomyces cerevisiae. Cell Cycle 2009, 7:1391-1401.
31. Petroski M.D., Deshaies R.J. Mechanism of lysine 48-linked ubiquitin-chain synthesis by the cullin-RING ubiquitin-ligase complex SCF-Cdc34. Cell 2005, 123:1107-1120.
32. Lass A., Cocklin R., Scaglione K.M., Skowyra M., Korolev S., Goebl M., Skowyra D. The loop-less tmCdc34 E2 mutant defective in polyubiquitination in vitro and in vivo supports yeast growth in a manner dependent on Ubp14 and Cka2. Cell Div. 2011, 6:7.
33. Ziemba A., Hill S., Sandoval D., Webb K., Bennett E.J., Kleiger G. Multimodal mechanism of action for the Cdc34 acidic loop: a case study for why ubiquitin-conjugating enzymes have loops and tails. J. Biol. Chem. 2013, 288:34882-34896.