Targeting NEDD8-activating enzyme for cancer therapy: developments, clinical trials, challenges and future research directions.

"table 1 x-ray structures of nae and nae complex enzyme/ligand name pdb code resolution (a) total structure weight (kda) atom count modeled residue count deposited residue count unique protein chains references nae(appbp1/uba3) 1yov 2 60 220 58 14604 1834 1962 2 [ ] appbp1/uba3/nedd8/atp 1r4n 3 60 469 48 31744 4040 4144 3 [ ] appbp1/uba3/nedd8 1r4m 3 00 467 45 31620 4040 4144 3 [ ] appbp1/uba3/ubc12 1tt5 2 60 223 43 14637 1866 1982 3 [ ] appbp1/uba3/nedd8/atp/ubc12 2nvu 2 80 188 89 13090 1647 1683 4 [ ] appbp1/uba3/nedd8 3dbr 3 05 474 00 32424 4098 4212 3 [ ] appbp1/uba3/nedd8 3dbl 2 90 474 32577 4121 4212 3 [ ] appbp1/uba3/nedd8 3dbh 2 85 473 77 32578 4123 4212 3 [ ] appbp1/uba3/nedd8/mln4924 3gzn 3 00 244 27 16050 2069 2158 3 [ ] the multistep mechanisms of nedd8 activation by nae are summarized in fig 3 .; chemical structures of mln4924 and tas4464 are shown in fig 4 a the co-crystal structure of nae and mln4924 (pdb: 3gzn resolution: 3 00 a) was reported in 2010 and shown in fig 4 b c [ ] g79 and r111 of nae form a hydrogen bond with the sulfonamide group of mln4924 (1 7 a and 2 7 a)."

"Declarations Ethics approval and consent to participateNot applicable. Consent for publicationNot applicable. Competing interestsThe authors declare that they have no competing interests. Competing interests The authors declare that they have no competing interests."

"Funding This work was supported by the Fundamental Research Funds for the Central Universities [Grant No. 2022-JYB-XJSJJ025 to Dong-Jun Fu]. This work was also funded by China Postdoctoral Science Foundation [Grant No. 2020M670239 to Dong-Jun Fu]."