Table 2. Rmsd values for comparison of the NMR structure of hMcl-1(171–327) with the structures of mouse mMcl-1(152–308) and Mcl-1complexes.a .
Mcl-1 structures | 172–193, 203–321b | α1–α7c | 209–321b | α2–α4d | α2–α7d | dCA224,252 d |
mMcl-1e | 1.60±0.09 | 1.52±0.06 | 1.61±0.10 | 1.21±0.07 | 1.53±0.06 | 13.2–14.6 |
hMcl-1-hBimf | 1.76±0.10 | 1.41±0.06 | 1.87±0.11 | 1.52±0.09 | 1.53±0.09 | 19.9 |
rMcl-1-hMcl-1-mNoxaBg | 1.46±0.12 | 1.05±0.08 | 1.53±0.14 | 1.00±0.10 | 1.08±0.09 | 19.9 |
mMcl-1-mNoxaA h | 1.52±0.11 | 1.16±0.07 | 1.59±0.13 | 1.11±0.11 | 1.18±0.08 | 18.8–20.2 |
mMcl-1-mPumai | 1.57±0.09 | 1.30±0.08 | 1.59±0.11 | 1.24±0.11 | 1.30±0.09 | 18.3–19.9 |
mMcl-1-mNoxaBj | 1.46±0.09 | 1.13±0.05 | 1.53±0.11 | 1.12±0.08 | 1.18±0.06 | 18.3–19.6 |
rMcl-1-hMcl-1-hBimk | 1.75±0.09 | 1.44±0.06 | 1.86±0.11 | 1.58±0.09 | 1.56±0.07 | 19.9 |
rMcl-1-hMcl-1-hBim(L62A, F78A) l | 1.80±0.09 | 1.44±0.06 | 1.90±0.11 | 1.53±0.08 | 1.55±0.07 | 19.8 |
hMcl1-hBidBH3J | 1.84±0.15 | 1.54±0.09 | 1.57±0.20 | 1.30±0.15 | 1.30±0.12 | 20.8–21.4 |
hMcl1-hBIMBH3k | 1.38±0.16 | 1.06±0.07 | 1.43±0.18 | 0.93±0.10 | 1.09±0.09 | 19.4 |
hMcl1-BimL12Yl | 1.75±0.13 | 1.50±0.08 | 1.85±0.15 | 1.48±0.12 | 1.59±0.09 | 20.2 |
hMcl1-BimBH3 2dAm | 1.75±0.13 | 1.50±0.08 | 1.84±0.14 | 1.46±0.12 | 1.57±0.09 | 19.7 |
hMcl1-BimBH3 F4aEn | 1.75±0.13 | 1.47±0.08 | 1.84±0.15 | 1.44±0.08 | 1.55±0.08 | 19.9 |
hMcl1 -B7o | 1.73±0.14 | 1.46±0.08 | 1.83±0.11 | 1.42±0.11 | 1.54±0.08 | 19.6–19.9 |
hMcl1–hMcl1BH3p | 1.47±0.16 | 1.21±0.09 | 1.48±0.18 | 1.08±0.15 | 1.24±0.11 | 20.3 |
hMcl1-BaxBH3q | 1.69±0.12 | 1.46±0.08 | 1.79±0.13 | 1.43±0.12 | 1.54±0.09 | 19.4 |
mMcl1-NoxaBH3r | 1.43±0.16 | 1.20±0.10 | 1.48±0.17 | 1.10±0.13 | 1.23±0.11 | 19.1 |
hMcl1-compound53s | 1.45±0.12 | 1.22±0.08 | 1.48±0.14 | 1.19±0.10 | 1.28±0.08 | 18.7 |
hMcl1-compound60t | 1.45±0.13 | 1.22±0.08 | 1.47±0.12 | 1.12±0.09 | 1.25±0.08 | 17.9–19.6 |
hMcl1-BH3u | 1.51±0.16 | 1.22±0.09 | 1.57±0.18 | 1.06±0.12 | 1.27±0.10 | 20.3 |
Average pairwise rmsd values (Å) were calculated for backbone heavy atoms N, Cα, and C’ between the 20 conformers of Mcl-1(171–327) and corresponding polypeptide segments in the other structures. The distances dCA (in Å) between the Cα-atoms of residues His 224 in helix α2 (His 205 in mMcl-1) and His 252 (His 233 in mMcl-1) at the C-terminus of helix α3 are provided as a measure for the width of the BH3 binding groove.
Residue numbers are for hMcl-1(171–327); residues 194–202 were excluded since one structure (2nl9k) does not contain the corresponding residues; residues 172–193 and 203–321 correspond to residues 153–174 and 184–302 in mMcl-1, and residues 209–321 correspond to residues 190–302 in mMcl-1.
Helices α1–α7 in hMcl-1 comprise residues 173–191, 204–235, 240–253, 262–280, 284–301, 303–308 and 311–319; the corresponding residues in mMcl-1 are: 155–172, 185–216, 221–234, 243–261, 265–282, 284–289 and 292–300.
Helices α2–α7 in hMcl-1 and residues 204–208 (numbers in hMcl-1) were excluded
Mouse mMcl-1(152–308), PDB accession code 1wsx (the mean NMR coordinates were used) [10].
Human hMcl-1 complexed with human hBim BH3, 2pqk [11].
Chimiric rat-human rMcl-1(171–208)hMcl-1(209–327) complexed with mouse mNoxaB BH3, 2nla [9].
Mouse mMcl-1 complexed with mouse mNoxaA BH3, 2rod [12].
Mouse mMcl-1 complexed with mouse mPuma BH3, 2roc [12].
Mouse mMcl-1 complexed with mouse mNoxaB BH3, 2jm6 [9].
Chimiric rat-human Mcl-1 complexed with human hBim BH3, 2nl9 [9].
Chimiric rat-human Mcl-1 complexed with human hBim (L62A, F68A), 3d7v [13].
Human hMcl1 complexed with human Bid BH3, 2kbw [15].
Human hMcl-1 complexed with human Bim BH3 mutant I2dY, 3kj0 [11].
Human hMcl-1 complexed with human BimL12Y, 3io9 [16].
Human hMcl1 complexed with human Bim BH3 mutant I2dA, 3kj1 [11].
Human hMcl1 complexed with human Bim BH3 mutant F4aE, 3kj2 [11].
Human hMcl-1 complexed with Mcl1 specific selected peptide B7, 3kz0 [41].
Human hMcl-1 complexed with human Mcl1 BH3, 3mk8 [17].
Human hMcl1 complexed with human Bax BH3, 3pk1.
Mouse mMcl-1 complexed with mouse Noxa BH3, 4g35 [18].
Human hMcl-1 complexed with 6-chloro-3-[3-(4-chloro-3,5-dimethylphenoxy)propyl]-1H-indole-2-carboxylic acid, 4hw2 [14].
Human hMcl-1 complexed with 6-chloro-3-[3-(4-chloro-3,5-dimethylphenoxy)propyl]-1H-indole-2-carboxylic acid, 4hw3 [14].
Human hMcl-1 complexed with human Mcl1 BH3, 4hw4 [14].