PDB-8zmq: Crystal Structure of the second bromodomain of human BRD4 BD2 in ...

Basic information

• Entry: Database: PDB / ID: 8zmq
• Title: Crystal Structure of the second bromodomain of human BRD4 BD2 in complex with the inhibitor Y13190
• Components: BRD4_HUMAN
• Keywords: PROTEIN BINDING / BRD4 / BD2 / Bromodomain

Function / homology

Function:

RNA polymerase II C-terminal domain binding / P-TEFb complex binding / negative regulation of DNA damage checkpoint / histone H4 reader activity / host-mediated suppression of viral transcription / positive regulation of G2/M transition of mitotic cell cycle / positive regulation of T-helper 17 cell lineage commitment / : / RNA polymerase II CTD heptapeptide repeat kinase activity / condensed nuclear chromosome / transcription coregulator activity / positive regulation of transcription elongation by RNA polymerase II / p53 binding / chromosome / regulation of inflammatory response / histone binding / Potential therapeutics for SARS / transcription coactivator activity / positive regulation of canonical NF-kappaB signal transduction / transcription cis-regulatory region binding / chromatin remodeling / protein serine/threonine kinase activity / DNA damage response / chromatin binding / regulation of transcription by RNA polymerase II / chromatin / positive regulation of DNA-templated transcription / enzyme binding / positive regulation of transcription by RNA polymerase II / nucleoplasm / nucleus

Domain/homology:

Bromodomain protein 4, C-terminal / C-terminal domain of bromodomain protein 4 / Brdt, bromodomain, repeat I / Brdt, bromodomain, repeat II / NET domain superfamily / NET domain profile. / : / NET domain / Bromodomain extra-terminal - transcription regulation / Bromodomain, conserved site / Bromodomain signature. / Bromodomain / bromo domain / Bromodomain / Bromodomain (BrD) profile. / Bromodomain-like superfamily

Component:

: / Bromodomain-containing protein 4

• Biological species: Homo sapiens (human)
• Method: X-RAY DIFFRACTION / SYNCHROTRON / MOLECULAR REPLACEMENT / Resolution: 2.2 Å
• Authors: Li, J. / Hu, Q. / Xu, H. / Zhao, X. / Zhang, C. / Zhu, R. / Wu, X. / Zhang, Y. / Xu, Y.

Funding support

China, 1items

Organization	Grant number	Country
National Natural Science Foundation of China (NSFC)	81673357	China

• Citation: Journal: J.Med.Chem. / Year: 2024; Title: Discovery of the First BRD4 Second Bromodomain (BD2)-Selective Inhibitors.; Authors: Li, J. / Hu, Q. / Zhu, R. / Dong, R. / Shen, H. / Hu, J. / Zhang, C. / Zhang, X. / Xu, T. / Xiang, Q. / Zhang, Y. / Lin, B. / Zhao, L. / Wu, X. / Xu, Y.

History

Deposition	May 23, 2024	Deposition site: PDBJ / Processing site: PDBJ
Revision 1.0	Dec 11, 2024	Provider: repository / Type: Initial release
Revision 1.1	Dec 25, 2024	Group: Database references / Category: citation / citation_author Item: _citation.journal_volume / _citation.page_first / _citation.page_last / _citation_author.identifier_ORCID

Assembly

Deposited unit

A: BRD4_HUMAN

B: BRD4_HUMAN

C: BRD4_HUMAN

D: BRD4_HUMAN

E: BRD4_HUMAN

F: BRD4_HUMAN

G: BRD4_HUMAN

H: BRD4_HUMAN

I: BRD4_HUMAN

J: BRD4_HUMAN

K: BRD4_HUMAN

L: BRD4_HUMAN

M: BRD4_HUMAN

N: BRD4_HUMAN

O: BRD4_HUMAN

P: BRD4_HUMAN

Q: BRD4_HUMAN

R: BRD4_HUMAN

S: BRD4_HUMAN

T: BRD4_HUMAN

hetero molecules

Summary:

• 356 kDa, 20 polymers

Component details:

	Theoretical mass	Number of molelcules
Total (without water)	355,750	46
Polymers	342,272	20
Non-polymers	13,479	26
Water	2,216	123

1

A: BRD4_HUMAN

hetero molecules

Summary:

• defined by author
• 17.8 kDa, 1 polymers

Component details:

	Theoretical mass	Number of molelcules
Total (without water)	17,842	3
Polymers	17,114	1
Non-polymers	728	2
Water	18	1

Symmetry operations:

Type	Name	Symmetry operation	Number
identity operation	1_555	x,y,z	1

2

B: BRD4_HUMAN

hetero molecules

Summary:

• defined by author
• 17.9 kDa, 1 polymers

Component details:

	Theoretical mass	Number of molelcules
Total (without water)	17,920	4
Polymers	17,114	1
Non-polymers	806	3
Water	18	1

Symmetry operations:

Type	Name	Symmetry operation	Number
identity operation	1_555	x,y,z	1

3

C: BRD4_HUMAN

hetero molecules

Summary:

• defined by author
• 17.8 kDa, 1 polymers

Component details:

	Theoretical mass	Number of molelcules
Total (without water)	17,763	2
Polymers	17,114	1
Non-polymers	650	1
Water	18	1

Symmetry operations:

Type	Name	Symmetry operation	Number
identity operation	1_555	x,y,z	1

4

D: BRD4_HUMAN

hetero molecules

Summary:

• defined by author
• 17.8 kDa, 1 polymers

Component details:

	Theoretical mass	Number of molelcules
Total (without water)	17,763	2
Polymers	17,114	1
Non-polymers	650	1
Water	18	1

Symmetry operations:

Type	Name	Symmetry operation	Number
identity operation	1_555	x,y,z	1

5

E: BRD4_HUMAN

hetero molecules

Summary:

• defined by author
• 17.8 kDa, 1 polymers

Component details:

	Theoretical mass	Number of molelcules
Total (without water)	17,763	2
Polymers	17,114	1
Non-polymers	650	1
Water	18	1

Symmetry operations:

Type	Name	Symmetry operation	Number
identity operation	1_555	x,y,z	1

6

F: BRD4_HUMAN

hetero molecules

Summary:

• defined by author
• 17.8 kDa, 1 polymers

Component details:

	Theoretical mass	Number of molelcules
Total (without water)	17,763	2
Polymers	17,114	1
Non-polymers	650	1
Water	18	1

Symmetry operations:

Type	Name	Symmetry operation	Number
identity operation	1_555	x,y,z	1

7

G: BRD4_HUMAN

hetero molecules

Summary:

• defined by author
• 17.8 kDa, 1 polymers

Component details:

	Theoretical mass	Number of molelcules
Total (without water)	17,763	2
Polymers	17,114	1
Non-polymers	650	1
Water	18	1

Symmetry operations:

Type	Name	Symmetry operation	Number
identity operation	1_555	x,y,z	1

8

H: BRD4_HUMAN

hetero molecules

Summary:

• defined by author
• 17.8 kDa, 1 polymers

Component details:

	Theoretical mass	Number of molelcules
Total (without water)	17,763	2
Polymers	17,114	1
Non-polymers	650	1
Water	18	1

Symmetry operations:

Type	Name	Symmetry operation	Number
identity operation	1_555	x,y,z	1

9

I: BRD4_HUMAN

hetero molecules

Summary:

• defined by author
• 17.8 kDa, 1 polymers

Component details:

	Theoretical mass	Number of molelcules
Total (without water)	17,763	2
Polymers	17,114	1
Non-polymers	650	1
Water	18	1

Symmetry operations:

Type	Name	Symmetry operation	Number
identity operation	1_555	x,y,z	1

10

J: BRD4_HUMAN

hetero molecules

Summary:

• defined by author
• 17.8 kDa, 1 polymers

Component details:

	Theoretical mass	Number of molelcules
Total (without water)	17,763	2
Polymers	17,114	1
Non-polymers	650	1
Water	18	1

Symmetry operations:

Type	Name	Symmetry operation	Number
identity operation	1_555	x,y,z	1

11

K: BRD4_HUMAN

hetero molecules

Summary:

• defined by author
• 17.8 kDa, 1 polymers

Component details:

	Theoretical mass	Number of molelcules
Total (without water)	17,763	2
Polymers	17,114	1
Non-polymers	650	1
Water	18	1

Symmetry operations:

Type	Name	Symmetry operation	Number
identity operation	1_555	x,y,z	1

12

L: BRD4_HUMAN

hetero molecules

Summary:

• defined by author
• 17.9 kDa, 1 polymers

Component details:

	Theoretical mass	Number of molelcules
Total (without water)	17,855	3
Polymers	17,114	1
Non-polymers	742	2
Water	18	1

Symmetry operations:

Type	Name	Symmetry operation	Number
identity operation	1_555	x,y,z	1

13

M: BRD4_HUMAN

hetero molecules

Summary:

• defined by author
• 17.8 kDa, 1 polymers

Component details:

	Theoretical mass	Number of molelcules
Total (without water)	17,842	3
Polymers	17,114	1
Non-polymers	728	2
Water	18	1

Symmetry operations:

Type	Name	Symmetry operation	Number
identity operation	1_555	x,y,z	1

14

N: BRD4_HUMAN

hetero molecules

Summary:

• defined by author
• 17.8 kDa, 1 polymers

Component details:

	Theoretical mass	Number of molelcules
Total (without water)	17,842	3
Polymers	17,114	1
Non-polymers	728	2
Water	18	1

Symmetry operations:

Type	Name	Symmetry operation	Number
identity operation	1_555	x,y,z	1

15

O: BRD4_HUMAN

hetero molecules

Summary:

• defined by author
• 17.8 kDa, 1 polymers

Component details:

	Theoretical mass	Number of molelcules
Total (without water)	17,763	2
Polymers	17,114	1
Non-polymers	650	1
Water	0

Symmetry operations:

Type	Name	Symmetry operation	Number
identity operation	1_555	x,y,z	1

16

P: BRD4_HUMAN

hetero molecules

Summary:

• defined by author
• 17.8 kDa, 1 polymers

Component details:

	Theoretical mass	Number of molelcules
Total (without water)	17,763	2
Polymers	17,114	1
Non-polymers	650	1
Water	0

Symmetry operations:

Type	Name	Symmetry operation	Number
identity operation	1_555	x,y,z	1

17

Q: BRD4_HUMAN

hetero molecules

Summary:

• defined by author
• 17.8 kDa, 1 polymers

Component details:

	Theoretical mass	Number of molelcules
Total (without water)	17,763	2
Polymers	17,114	1
Non-polymers	650	1
Water	0

Symmetry operations:

Type	Name	Symmetry operation	Number
identity operation	1_555	x,y,z	1

18

R: BRD4_HUMAN

hetero molecules

Summary:

• defined by author
• 17.8 kDa, 1 polymers

Component details:

	Theoretical mass	Number of molelcules
Total (without water)	17,763	2
Polymers	17,114	1
Non-polymers	650	1
Water	0

Symmetry operations:

Type	Name	Symmetry operation	Number
identity operation	1_555	x,y,z	1

19

S: BRD4_HUMAN

hetero molecules

Summary:

• defined by author
• 17.8 kDa, 1 polymers

Component details:

	Theoretical mass	Number of molelcules
Total (without water)	17,763	2
Polymers	17,114	1
Non-polymers	650	1
Water	18	1

Symmetry operations:

Type	Name	Symmetry operation	Number
identity operation	1_555	x,y,z	1

20

T: BRD4_HUMAN

hetero molecules

Summary:

• defined by author
• 17.8 kDa, 1 polymers

Component details:

	Theoretical mass	Number of molelcules
Total (without water)	17,763	2
Polymers	17,114	1
Non-polymers	650	1
Water	0

Symmetry operations:

Type	Name	Symmetry operation	Number
identity operation	1_555	x,y,z	1

Unit cell

Length a, b, c (Å)	115.913, 125.108, 300.352
Angle α, β, γ (deg.)	90.00, 90.04, 90.00
Int Tables number	5
Space group name H-M	C121

Noncrystallographic symmetry (NCS)

NCS domain:

ID	Ens-ID
1	1
2	2
3	3
4	4
5	5
6	6
7	7
8	8
9	9
10	10
11	11
12	12
13	13
14	14
15	15
16	16
17	17
18	18
19	19
20	20
21	21
22	22
23	23
24	24
25	25
26	26
27	27
28	28
29	29
30	30
31	31
32	32
33	33
34	34
35	35
36	36
37	37
38	38
39	39
40	40
41	41
42	42
43	43
44	44
45	45
46	46
47	47
48	48
49	49
50	50
51	51
52	52
53	53
54	54
55	55
56	56
57	57
58	58
59	59
60	60
61	61
62	62
63	63
64	64
65	65
66	66
67	67
68	68
69	69
70	70
71	71
72	72
73	73
74	74
75	75
76	76
77	77
78	78
79	79
80	80
81	81
82	82
83	83
84	84
85	85
86	86
87	87
88	88
89	89
90	90
91	91
92	92
93	93
94	94
95	95
96	96
97	97
98	98
99	99
100	100
101	101
102	102
103	103
104	104
105	105
106	106
107	107
108	108
109	109
110	110
111	111
112	112
113	113
114	114
115	115
116	116
117	117
118	118
119	119
120	120
121	121
122	122
123	123
124	124
125	125
126	126
127	127
128	128
129	129
130	130
131	131
132	132
133	133
134	134
135	135
136	136
137	137
138	138
139	139
140	140
141	141
142	142
143	143
144	144
145	145
146	146
147	147
148	148
149	149
150	150
151	151
152	152
153	153
154	154
155	155
156	156
157	157
158	158
159	159
160	160
161	161
162	162
163	163
164	164
165	165
166	166
167	167
168	168
169	169
170	170
171	171
172	172
173	173
174	174
175	175
176	176
177	177
178	178
179	179
180	180
181	181
182	182
183	183
184	184
185	185
186	186
187	187
188	188
189	189
190	190

NCS ensembles :

ID
1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
61
62
63
64
65
66
67
68
69
70
71
72
73
74
75
76
77
78
79
80
81
82
83
84
85
86
87
88
89
90
91
92
93
94
95
96
97
98
99
100
101
102
103
104
105
106
107
108
109
110
111
112
113
114
115
116
117
118
119
120
121
122
123
124
125
126
127
128
129
130
131
132
133
134
135
136
137
138
139
140
141
142
143
144
145
146
147
148
149
150
151
152
153
154
155
156
157
158
159
160
161
162
163
164
165
166
167
168
169
170
171
172
173
174
175
176
177
178
179
180
181
182
183
184
185
186
187
188
189
190

Components

#1: Protein

A B C D E F G H I J K L M N O P Q R S T
BRD4_HUMAN / Protein HUNK1 / Bromodomain-containing protein 4

Details:

Mass: 17113.584 Da / Num. of mol.: 20
Source method: isolated from a genetically manipulated source
Details: BRD4_HUMAN, O60885, sequence from 308-331 are tags. EGDIHMKKGHHHHHHENLYFQGGS
Source: (gene. exp.) Homo sapiens (human) / Gene: BRD4, HUNK1 / Production host: Escherichia coli (E. coli) / References: UniProt: O60885

#2: Chemical

A-501 B-502 C-501 D-501 E-501 F-501 G-501 H-501 I-501 J-501 K-501 L-501 M-501 N-501 O-501 P-501 Q-501 R-501 S-501 T-501
ChemComp-A1L12 / 2-(2-(adamantan-1-yl)-4-ethyl-1H-imidazol-5-yl)-7-(2-(4-fluoro-2,6-dimethylphenoxy)-5-(2-hydroxypropan-2-yl)phenyl)-5-methylfuro[3,2-c]pyridin-4(5H)-one

Details:

Mass: 649.793 Da / Num. of mol.: 20 / Source method: obtained synthetically / Formula: C₄₀H₄₄FN₃O₄ / Feature type: SUBJECT OF INVESTIGATION

#3: Chemical

A-502 B-501 B-503 M-502 N-502
ChemComp-DMS / DIMETHYL SULFOXIDE

Details:

Mass: 78.133 Da / Num. of mol.: 5 / Source method: obtained synthetically / Formula: C₂H₆OS / Feature type: SUBJECT OF INVESTIGATION / Comment: DMSO, precipitant*YM

#4: Chemical

L-502 ChemComp-GOL / GLYCEROL / GLYCERIN / PROPANE-1,2,3-TRIOL

Details:

Mass: 92.094 Da / Num. of mol.: 1 / Source method: obtained synthetically / Formula: C₃H₈O₃ / Feature type: SUBJECT OF INVESTIGATION

#5: Water

ChemComp-HOH / water

Details:

Mass: 18.015 Da / Num. of mol.: 123 / Source method: isolated from a natural source / Formula: H₂O

• Has ligand of interest: Y
• Has protein modification: N

Experimental details

Experiment

• Experiment: Method: X-RAY DIFFRACTION / Number of used crystals: 1

Sample preparation

• Crystal: Density Matthews: 3.08 ų/Da / Density % sol: 60.09 %
• Crystal grow: Temperature: 277 K / Method: vapor diffusion, sitting drop; Details: 0.01 M Iron(III) chloride hexahydrate, 0.1 M Sodium citrate tribasic dihydrate pH 5.6, 10% v/v Jeffamine M-600

Data collection

• Diffraction: Mean temperature: 80 K / Serial crystal experiment: N
• Diffraction source: Source: SYNCHROTRON / Site: SSRF / Beamline: BL18U1 / Wavelength: 0.97918 Å
• Detector: Type: DECTRIS PILATUS3 6M / Detector: PIXEL / Date: Mar 22, 2024
• Radiation: Protocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray
• Radiation wavelength: Wavelength: 0.97918 Å / Relative weight: 1
• Reflection: Resolution: 2.2→300.35 Å / Num. obs: 217025 / % possible obs: 100 % / Redundancy: 6.8 % / CC_1/2: 0.997 / R_merge(I) obs: 0.155 / R_pim(I) all: 0.064 / R_rim(I) all: 0.168 / Χ²: 0.9 / Net I/σ(I): 6 / Num. measured all: 1479344
• Reflection shell: Resolution: 2.2→2.24 Å / % possible obs: 100 % / Redundancy: 6.7 % / R_merge(I) obs: 2.487 / Num. measured all: 71440 / Num. unique obs: 10729 / CC_1/2: 0.286 / R_pim(I) all: 1.04 / R_rim(I) all: 2.7 / Χ²: 0.88 / Net I/σ(I) obs: 0.7

Processing

Software

Name	Version	Classification
REFMAC	5.8.0258	refinement
Aimless		data scaling
DIALS		data reduction
MOLREP		phasing

Refinement

Method to determine structure: MOLECULAR REPLACEMENT
Starting model: 6IVX

6ivx

Resolution: 2.2→300.35 Å / Cor.coef. F_o:F_c: 0.943 / Cor.coef. F_o:F_c free: 0.934 / SU B: 11.695 / SU ML: 0.25 / Cross valid method: THROUGHOUT / ESU R: 0.22 / ESU R Free: 0.187 / Stereochemistry target values: MAXIMUM LIKELIHOOD / Details: HYDROGENS HAVE BEEN ADDED IN THE RIDING POSITIONS

	Rfactor	Num. reflection	% reflection	Selection details
Rfree	0.27444	10956	5.1 %	RANDOM
Rwork	0.25628	-	-	-
obs	0.2572	205956	99.95 %	-

• Solvent computation: Ion probe radii: 0.8 Å / Shrinkage radii: 0.8 Å / VDW probe radii: 1.2 Å / Solvent model: MASK

Displacement parameters

B_iso mean: 65.457 Ų

	Baniso -1	Baniso -2	Baniso -3
1-	-3.39 Å2	-0 Å2	-0.06 Å2
2-	-	-0.99 Å2	0 Å2
3-	-	-	4.38 Å2

Refinement step

Cycle: 1 / Resolution: 2.2→300.35 Å

	Protein	Nucleic acid	Ligand	Solvent	Total
Num. atoms	17934	0	986	123	19043

Refine LS restraints

Refine-ID	Type	Dev ideal	Dev ideal target	Number
X-RAY DIFFRACTION	r_bond_refined_d	0.009	0.014	19578
X-RAY DIFFRACTION	r_bond_other_d	0.003	0.018	18056
X-RAY DIFFRACTION	r_angle_refined_deg	1.847	1.731	26563
X-RAY DIFFRACTION	r_angle_other_deg	1.363	1.666	41979
X-RAY DIFFRACTION	r_dihedral_angle_1_deg	5.128	5	2197
X-RAY DIFFRACTION	r_dihedral_angle_2_deg	35.779	22.423	978
X-RAY DIFFRACTION	r_dihedral_angle_3_deg	19.476	15	3428
X-RAY DIFFRACTION	r_dihedral_angle_4_deg	18.474	15	100
X-RAY DIFFRACTION	r_chiral_restr	0.203	0.2	2349
X-RAY DIFFRACTION	r_gen_planes_refined	0.004	0.02	21084
X-RAY DIFFRACTION	r_gen_planes_other	0.001	0.02	4092
X-RAY DIFFRACTION	r_nbd_refined
X-RAY DIFFRACTION	r_nbd_other
X-RAY DIFFRACTION	r_nbtor_refined
X-RAY DIFFRACTION	r_nbtor_other
X-RAY DIFFRACTION	r_xyhbond_nbd_refined
X-RAY DIFFRACTION	r_xyhbond_nbd_other
X-RAY DIFFRACTION	r_metal_ion_refined
X-RAY DIFFRACTION	r_metal_ion_other
X-RAY DIFFRACTION	r_symmetry_vdw_refined
X-RAY DIFFRACTION	r_symmetry_vdw_other
X-RAY DIFFRACTION	r_symmetry_hbond_refined
X-RAY DIFFRACTION	r_symmetry_hbond_other
X-RAY DIFFRACTION	r_symmetry_metal_ion_refined
X-RAY DIFFRACTION	r_symmetry_metal_ion_other
X-RAY DIFFRACTION	r_mcbond_it	2.769	6.857	8803
X-RAY DIFFRACTION	r_mcbond_other	2.768	6.857	8802
X-RAY DIFFRACTION	r_mcangle_it	4.561	10.265	10974
X-RAY DIFFRACTION	r_mcangle_other	4.561	10.266	10975
X-RAY DIFFRACTION	r_scbond_it	2.748	6.994	10775
X-RAY DIFFRACTION	r_scbond_other	2.748	6.994	10776
X-RAY DIFFRACTION	r_scangle_it
X-RAY DIFFRACTION	r_scangle_other	4.735	10.332	15583
X-RAY DIFFRACTION	r_long_range_B_refined	7.339	74.475	23063
X-RAY DIFFRACTION	r_long_range_B_other	7.339	74.483	23051
X-RAY DIFFRACTION	r_rigid_bond_restr
X-RAY DIFFRACTION	r_sphericity_free
X-RAY DIFFRACTION	r_sphericity_bonded

Refine LS restraints NCS

Refine-ID: X-RAY DIFFRACTION / Type: interatomic distance / Weight position: 0.05

Ens-ID	Dom-ID	Auth asym-ID	Number	Rms dev position (Å)
1	1	A	3646	0.05
1	2	B	3646	0.05
2	1	A	3629	0.05
2	2	C	3629	0.05
3	1	A	3631	0.05
3	2	D	3631	0.05
4	1	A	3666	0.04
4	2	E	3666	0.04
5	1	A	3647	0.04
5	2	F	3647	0.04
6	1	A	3633	0.05
6	2	G	3633	0.05
7	1	A	3627	0.05
7	2	H	3627	0.05
8	1	A	3595	0.04
8	2	I	3595	0.04
9	1	A	3603	0.04
9	2	J	3603	0.04
10	1	A	3659	0.04
10	2	K	3659	0.04
11	1	A	3659	0.04
11	2	L	3659	0.04
12	1	A	3606	0.04
12	2	M	3606	0.04
13	1	A	3593	0.04
13	2	N	3593	0.04
14	1	A	3573	0.05
14	2	O	3573	0.05
15	1	A	3585	0.04
15	2	P	3585	0.04
16	1	A	3569	0.07
16	2	Q	3569	0.07
17	1	A	3584	0.05
17	2	R	3584	0.05
18	1	A	3600	0.07
18	2	S	3600	0.07
19	1	A	3571	0.05
19	2	T	3571	0.05
20	1	B	3621	0.06
20	2	C	3621	0.06
21	1	B	3623	0.05
21	2	D	3623	0.05
22	1	B	3629	0.06
22	2	E	3629	0.06
23	1	B	3615	0.06
23	2	F	3615	0.06
24	1	B	3621	0.05
24	2	G	3621	0.05
25	1	B	3615	0.05
25	2	H	3615	0.05
26	1	B	3578	0.05
26	2	I	3578	0.05
27	1	B	3583	0.05
27	2	J	3583	0.05
28	1	B	3646	0.05
28	2	K	3646	0.05
29	1	B	3638	0.06
29	2	L	3638	0.06
30	1	B	3599	0.05
30	2	M	3599	0.05
31	1	B	3585	0.05
31	2	N	3585	0.05
32	1	B	3544	0.05
32	2	O	3544	0.05
33	1	B	3560	0.06
33	2	P	3560	0.06
34	1	B	3548	0.07
34	2	Q	3548	0.07
35	1	B	3575	0.05
35	2	R	3575	0.05
36	1	B	3575	0.08
36	2	S	3575	0.08
37	1	B	3551	0.06
37	2	T	3551	0.06
38	1	C	3656	0.06
38	2	D	3656	0.06
39	1	C	3602	0.05
39	2	E	3602	0.05
40	1	C	3654	0.06
40	2	F	3654	0.06
41	1	C	3655	0.06
41	2	G	3655	0.06
42	1	C	3664	0.07
42	2	H	3664	0.07
43	1	C	3574	0.04
43	2	I	3574	0.04
44	1	C	3605	0.04
44	2	J	3605	0.04
45	1	C	3620	0.04
45	2	K	3620	0.04
46	1	C	3603	0.05
46	2	L	3603	0.05
47	1	C	3617	0.05
47	2	M	3617	0.05
48	1	C	3624	0.03
48	2	N	3624	0.03
49	1	C	3571	0.06
49	2	O	3571	0.06
50	1	C	3584	0.06
50	2	P	3584	0.06
51	1	C	3555	0.07
51	2	Q	3555	0.07
52	1	C	3564	0.05
52	2	R	3564	0.05
53	1	C	3544	0.08
53	2	S	3544	0.08
54	1	C	3540	0.05
54	2	T	3540	0.05
55	1	D	3602	0.05
55	2	E	3602	0.05
56	1	D	3660	0.05
56	2	F	3660	0.05
57	1	D	3671	0.04
57	2	G	3671	0.04
58	1	D	3672	0.04
58	2	H	3672	0.04
59	1	D	3569	0.05
59	2	I	3569	0.05
60	1	D	3609	0.04
60	2	J	3609	0.04
61	1	D	3615	0.04
61	2	K	3615	0.04
62	1	D	3605	0.04
62	2	L	3605	0.04
63	1	D	3620	0.03
63	2	M	3620	0.03
64	1	D	3601	0.05
64	2	N	3601	0.05
65	1	D	3572	0.05
65	2	O	3572	0.05
66	1	D	3592	0.05
66	2	P	3592	0.05
67	1	D	3539	0.06
67	2	Q	3539	0.06
68	1	D	3562	0.04
68	2	R	3562	0.04
69	1	D	3549	0.07
69	2	S	3549	0.07
70	1	D	3536	0.05
70	2	T	3536	0.05
71	1	E	3617	0.04
71	2	F	3617	0.04
72	1	E	3608	0.06
72	2	G	3608	0.06
73	1	E	3606	0.06
73	2	H	3606	0.06
74	1	E	3572	0.05
74	2	I	3572	0.05
75	1	E	3580	0.04
75	2	J	3580	0.04
76	1	E	3632	0.05
76	2	K	3632	0.05
77	1	E	3621	0.05
77	2	L	3621	0.05
78	1	E	3581	0.05
78	2	M	3581	0.05
79	1	E	3569	0.05
79	2	N	3569	0.05
80	1	E	3545	0.06
80	2	O	3545	0.06
81	1	E	3559	0.05
81	2	P	3559	0.05
82	1	E	3543	0.07
82	2	Q	3543	0.07
83	1	E	3548	0.05
83	2	R	3548	0.05
84	1	E	3571	0.08
84	2	S	3571	0.08
85	1	E	3546	0.06
85	2	T	3546	0.06
86	1	F	3670	0.05
86	2	G	3670	0.05
87	1	F	3660	0.05
87	2	H	3660	0.05
88	1	F	3573	0.05
88	2	I	3573	0.05
89	1	F	3613	0.05
89	2	J	3613	0.05
90	1	F	3611	0.05
90	2	K	3611	0.05
91	1	F	3614	0.04
91	2	L	3614	0.04
92	1	F	3623	0.04
92	2	M	3623	0.04
93	1	F	3603	0.05
93	2	N	3603	0.05
94	1	F	3581	0.05
94	2	O	3581	0.05
95	1	F	3592	0.05
95	2	P	3592	0.05
96	1	F	3554	0.07
96	2	Q	3554	0.07
97	1	F	3568	0.05
97	2	R	3568	0.05
98	1	F	3558	0.08
98	2	S	3558	0.08
99	1	F	3554	0.05
99	2	T	3554	0.05
100	1	G	3662	0.04
100	2	H	3662	0.04
101	1	G	3570	0.05
101	2	I	3570	0.05
102	1	G	3611	0.04
102	2	J	3611	0.04
103	1	G	3611	0.04
103	2	K	3611	0.04
104	1	G	3602	0.05
104	2	L	3602	0.05
105	1	G	3623	0.04
105	2	M	3623	0.04
106	1	G	3605	0.05
106	2	N	3605	0.05
107	1	G	3568	0.05
107	2	O	3568	0.05
108	1	G	3589	0.05
108	2	P	3589	0.05
109	1	G	3536	0.07
109	2	Q	3536	0.07
110	1	G	3560	0.05
110	2	R	3560	0.05
111	1	G	3543	0.08
111	2	S	3543	0.08
112	1	G	3542	0.05
112	2	T	3542	0.05
113	1	H	3586	0.05
113	2	I	3586	0.05
114	1	H	3607	0.05
114	2	J	3607	0.05
115	1	H	3616	0.05
115	2	K	3616	0.05
116	1	H	3605	0.06
116	2	L	3605	0.06
117	1	H	3621	0.05
117	2	M	3621	0.05
118	1	H	3615	0.05
118	2	N	3615	0.05
119	1	H	3573	0.06
119	2	O	3573	0.06
120	1	H	3592	0.05
120	2	P	3592	0.05
121	1	H	3549	0.07
121	2	Q	3549	0.07
122	1	H	3566	0.05
122	2	R	3566	0.05
123	1	H	3542	0.08
123	2	S	3542	0.08
124	1	H	3540	0.06
124	2	T	3540	0.06
125	1	I	3568	0.04
125	2	J	3568	0.04
126	1	I	3578	0.03
126	2	K	3578	0.03
127	1	I	3574	0.04
127	2	L	3574	0.04
128	1	I	3578	0.04
128	2	M	3578	0.04
129	1	I	3566	0.04
129	2	N	3566	0.04
130	1	I	3528	0.05
130	2	O	3528	0.05
131	1	I	3550	0.05
131	2	P	3550	0.05
132	1	I	3551	0.07
132	2	Q	3551	0.07
133	1	I	3578	0.05
133	2	R	3578	0.05
134	1	I	3506	0.07
134	2	S	3506	0.07
135	1	I	3549	0.05
135	2	T	3549	0.05
136	1	J	3596	0.04
136	2	K	3596	0.04
137	1	J	3578	0.04
137	2	L	3578	0.04
138	1	J	3639	0.05
138	2	M	3639	0.05
139	1	J	3627	0.04
139	2	N	3627	0.04
140	1	J	3597	0.06
140	2	O	3597	0.06
141	1	J	3613	0.06
141	2	P	3613	0.06
142	1	J	3538	0.08
142	2	Q	3538	0.08
143	1	J	3559	0.05
143	2	R	3559	0.05
144	1	J	3521	0.08
144	2	S	3521	0.08
145	1	J	3544	0.05
145	2	T	3544	0.05
146	1	K	3653	0.04
146	2	L	3653	0.04
147	1	K	3603	0.03
147	2	M	3603	0.03
148	1	K	3587	0.04
148	2	N	3587	0.04
149	1	K	3550	0.05
149	2	O	3550	0.05
150	1	K	3563	0.05
150	2	P	3563	0.05
151	1	K	3543	0.07
151	2	Q	3543	0.07
152	1	K	3574	0.04
152	2	R	3574	0.04
153	1	K	3574	0.08
153	2	S	3574	0.08
154	1	K	3546	0.05
154	2	T	3546	0.05
155	1	L	3582	0.03
155	2	M	3582	0.03
156	1	L	3568	0.04
156	2	N	3568	0.04
157	1	L	3533	0.06
157	2	O	3533	0.06
158	1	L	3554	0.05
158	2	P	3554	0.05
159	1	L	3525	0.07
159	2	Q	3525	0.07
160	1	L	3569	0.04
160	2	R	3569	0.04
161	1	L	3561	0.08
161	2	S	3561	0.08
162	1	L	3534	0.05
162	2	T	3534	0.05
163	1	M	3633	0.05
163	2	N	3633	0.05
164	1	M	3586	0.05
164	2	O	3586	0.05
165	1	M	3612	0.05
165	2	P	3612	0.05
166	1	M	3541	0.06
166	2	Q	3541	0.06
167	1	M	3562	0.05
167	2	R	3562	0.05
168	1	M	3519	0.07
168	2	S	3519	0.07
169	1	M	3544	0.05
169	2	T	3544	0.05
170	1	N	3592	0.06
170	2	O	3592	0.06
171	1	N	3600	0.06
171	2	P	3600	0.06
172	1	N	3546	0.06
172	2	Q	3546	0.06
173	1	N	3556	0.05
173	2	R	3556	0.05
174	1	N	3507	0.07
174	2	S	3507	0.07
175	1	N	3534	0.05
175	2	T	3534	0.05
176	1	O	3587	0.06
176	2	P	3587	0.06
177	1	O	3530	0.07
177	2	Q	3530	0.07
178	1	O	3541	0.05
178	2	R	3541	0.05
179	1	O	3510	0.08
179	2	S	3510	0.08
180	1	O	3532	0.06
180	2	T	3532	0.06
181	1	P	3531	0.06
181	2	Q	3531	0.06
182	1	P	3534	0.05
182	2	R	3534	0.05
183	1	P	3513	0.07
183	2	S	3513	0.07
184	1	P	3528	0.06
184	2	T	3528	0.06
185	1	Q	3537	0.07
185	2	R	3537	0.07
186	1	Q	3533	0.07
186	2	S	3533	0.07
187	1	Q	3543	0.07
187	2	T	3543	0.07
188	1	R	3497	0.08
188	2	S	3497	0.08
189	1	R	3552	0.06
189	2	T	3552	0.06
190	1	S	3506	0.08
190	2	T	3506	0.08

LS refinement shell

Resolution: 2.2→2.257 Å / Total num. of bins used: 20

	Rfactor	Num. reflection	% reflection
Rfree	0.443	762	-
Rwork	0.449	15274	-
obs	-	-	99.95 %