Y. Kawakita et al. / Bioorg. Med. Chem. 21 (2013) 2250–2261
2261
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X-ray data collection and refinement statistics
Compound 20a
Compound 19b
P212121
Data collection
Space group
P212121
Unit cell dimensions
a, b, c (Å)
46.4, 68.3, 103.3
90, 90, 90
50–1.80 (1.83–1.80)
148,774
30,817
4.8 (4.9)
99.7 (99.9)
26.1 (2.0)
0.054 (0.898)
46.9, 69.2, 104.4
90, 90, 90
50–1.70 (1.73–1.70)
166,963
38,002
4.4 (4.0)
99.7 (99.9)
26.2 (1.8)
0.049 (0.810)
a
, b, c (°)
Resolution (Å)
Observed reflections
Unique reflections
Redundancy
Completeness (%)
I/r (I)
a
Rsym
Refinement
Resolution (Å)
Reflections
40–1.80 (1.85–1.80)
29,094
0.205 (0.282)
0.233 (0.292)
40–1.70 (1.75–1.70)
35,911
0.202 (0.327)
0.232 (0.381)
b
Rcryst
b
Rfree
Number of atoms
Proteins
Ligand/ion
2541
44
79
2450
40
114
26.2
Water
Average B value (Å2)
32.7
RMS demivation from ideal geometry
Bond lengths (Å)
Bond angles (°)
0.009
1.220
0.009
1.262
Ramachandran plot (%)
Preferred regions
Allowed regions
Outliers
97.2
1.4
1.4
97.5
2.2
0.3
PDB code
3W32
3W33
a
Rsym
=
R
h
R
j| h I(h) i ꢀ I(h)j|/
R
h
R
j h I(h) i, where h I(h) i is the mean intensity of
symmetry-related reflections.
b
Rcryst
=
R
||Fobs| ꢀ |Fcalc||/ |Fobs|. Rfree was calculated for randomly chosen 5% of
R
reflections excluded from refinement. Values in parentheses are for the highest
resolution shell.
data were reduced and scaled using the HKL2000 software pack-
age.9 The structures were solved by molecular replacement with
the program MOLREP10 of the CCP4 program suite11 using the
EGFR/TAK-285 structure (PDB code: 3POZ) as a search model. Sev-
eral cycles of model building with Coot12 and refinement with Ref-
mac13 were performed for improving the quality of the model. The
dictionary files for the ligands were prepared using AFITT (Open-
Eye Scientific Software, USA). The final models were validated
using Molprobity.14 All structural figures were generated using Py-
MOL (Schrödinger, USA). Crystallographic processing and refine-
ment statistics are summarized in Supplementary data. The
coordinates and structure factors have been deposited in PDB with
accession codes 3W33 and 3W32 for 19b and 20a, respectively
(Table 3).
3. (a) Ishikawa, T.; Seto, M.; Banno, H.; Kawakita, Y.; Oorui, M.; Taniguchi, T.;
Ohta, Y.; Tamura, T.; Nakayama, A.; Miki, H.; Kamiguchi, H.; Tanaka, T.; Habuka,
N.; Sogabe, S.; Aertgeerts, K.; Kamiyama, K. J. Med. Chem. 2011, 54, 8030; (b)
Doi, T.; Takiuchi, H.; Ohtsu, A.; Fuse, N.; Goto, M.; Yoshida, M.; Dote, N.; Kuze,
Y.; Jinno, F.; Fujimoto, M.; Takubo, T.; Nakayama, N.; Tsutsumi, R. Br. J. Can.
2012, 106, 1.
4. Aertgeerts, K.; Skene, R.; Yano, J.; Sang, B.; Zou, H.; Snell, G.; Jennings, A.;
Iwamoto, K.; Habuka, N.; Hirokawa, A.; Ishikawa, T.; Tanaka, T.; Miki, H.; Ohta,
Y.; Sogabe, S. J. Biol. Chem. 2011, 21, 18756.
5. (a) Ikemoto, T.; Ito, T.; Nishiguchi, A.; Tomimatsu, K. Tetrahedron 2004, 60,
10851–10857; (b) Ikemoto, T.; Ito, T.; Nishiguchi, A.; Tomimatsu, K.
Tetrahedron Lett. 2004, 45, 9335–9339; (c) Seto, M.; Miyamoto, N.; Aikawa,
K.; Aramaki, Y.; Kanzaki, N.; Iizawa, Y.; Baba, M.; Shiraishi, M. Bioorg. Med.
Chem. 2005, 13, 363–386.
6. Clark, J.; Parvizi, B.; Southon, W. I. J. Chem. Soc., Perkin Trans. 1 1976, 2, 125.
7. Kawakita, Y.; Banno, H.; Ohashi, T.; Tamura, T.; Yusa, T.; Nakayama, A.; Miki, H.;
Iwata, H.; Kamiguchi, H.; Tanaka, T.; Habuka, N.; Sogabe, S.; Ohta, Y.; Ishikawa,
T. J. Med. Chem. 2012, 55, 3975.
References and notes
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11. Bailey, S. Acta Crystallogr. 1994, D50, 760.
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Cell 1983, 35, 71; (b) Traxler, P. Expert Opin. Ther. Targets 2003, 7, 215; (c) Nagar,
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