Supplementary Material
Table S1. List of residues found within 5 Å of the heme of each of the five CYP proteins (one
from each class of CYP). These residues are the same as those found in x- and y- axes of the
submatrices (DCCM) in Figure 5. Residue numbers are displayed, along with the structural motif
in which they exist. Helix structures are referred to by their English letter name (A-L) and beta
sheet structures are referred to as the Greek letter beta (β) and a number. Loop structures are
named using the helix and/or beta sheet motifs that flank them. The critical cysteine residue
numbers are underlined in the meander motif of each protein.
CYP class
PDB code Used
Residues
within 5 Å of Heme
Structural motif
Bacterial
1Z8O
M90, G91
H98, R102, F109
G242, A245, S246, L249
L282
P288
T291, R293, E297
S343, F344, G345, I348,
H349, F350, C351, M352
G353, L356, A357
R98, V113, I114
W121, R125, M132
L295, A298, G299, T302,
T303, T306
Q357
I363
V367, H369
P428, F429, S430, R434, I435,
C436, L437, G438
I441, A442, L446
K69, L86, F87
W96, H100, F107
I153
F261, A264, G265, T268,
T269, L272
B-C Loop
C Helix
I Helix
K Helix
K- β1 Loop
β1
Meander
CYB5R/cyb
Microsomal
3MVR
1BVY
L Helix
B-C Loop
C Helix
I Helix
K Helix
K- β1 Loop
β1
Meander
L Helix
B-C Loop
C Helix
E Helix
I Helix
1
Mitochondrial
P450 Only
3MZS
2RCH
T327, A328
F331
P392, F393, G394, R398,
A399, C400
I401, G402, Q403, F405, A406
K- β1 Loop
β1
Meander
R82
V101, L102
W109, R113
I172
E283, M284, G287, G288
T291, T292, T295
L346
I351, S352
L355, R357
G415, F416, G417, W418,
R421, Q422, C423, V424
G425, A429, M433
K133, F137, L154, S155
H164, L171, L175
N321, T322, G325, M326,
L329
P387, V388, Q391
W455, S456, N457, N468,
K469, Q470, C471, A472
G473, F476, V477
B1-B2 Loop
B2-C Loop
C Helix
E Helix
I Helix
L Helix
K Helix
K- β1 Loop
β1
Meander
L Helix
B-C Loop
C Helix
I Helix
K Helix
Meander
2
Table S2. The number of inter-residue contacts of residues exhibiting high/low atomic
fluctuations in the five representative CYP proteins.
Protein(s)
Residues
Number of inter-residue
contacts within 10 Å of the
selected residue
Intra-protein
2RCH
3MZS
1Z8O
64 and 360 (more flexible)
8 and 8
78 and 431(less flexible)
15 and 12
152 and 405 (more flexible)
9 and 7
107 and 388(less flexible)
11 and 18
66 and 221(more flexible)
5 and 6
81 and 328 (less flexible)
11 and 12
Inter-protein
3MZS and 2RCH
3MVR and 3MZS
1BVY and 3MVR
Between J-K helices
323 of 3MZS (more flexible)
12
360 of 2RCH (less flexible)
8
Between D-E helices
163 of 3MVR (more flexible)
15
152 of 3MZS (less flexible)
9
Between F and G
104 of 1BVY (less flexible)
10
226 of 3MVR (more flexible)
9
3
Table S3. Sequence similarity, sequence identity, structural similarity, and dynamic similarity
values for all pairwise comparisons between CYP proteins within CYP classes. Dynamic
similarity values are provided in terms of RMSIP and BC and represented as percentages
( RMSIP or BC ∗ 100).a
CYP class
Bacterial
PDB codes
%
Similarity
%
Identity
2BVJ
4APY
52
27
Structural
Similarity
(RMSD,
Å)
2.4
2BVJ
1Z8O
65
40
4APY
1Z8O
56
3G1Q
2F9Q
3G1Q
% Dynamic
Similarity
RMSIP
BC
64 (73)
81 (79)
1.9
71 (59)
83 (82)
25
2.6
74 (67)
85 (83)
49
20
3.2
59 (58)
80 (79)
3MVR
51
20
3.8
66 (73)
81 (78)
2F9Q
3MVR
71
43
2.3
69 (62)
84 (85)
1PQ2
1BVY
48
18
3.0
42 (38)
79 (75)
1PQ2
1W0E
57
25
3.1
67 (30)
83 (80)
1BVY 1W0E
54
23
2.7
37 (37)
78 (73)
Mitochondrial 3MZS 3K9Y
60
28
3.1
77 (67)
86 (81)
3MZS 3E4E
50
19
3.3
55 (42)
81 (74)
3K9Y
3E4E
53
20
3.8
58 (54)
80 (77)
2RCH 1CL6
40
13
3.1
54 (30)
80 (74)
2RCH 2IAG
43
17
4.1
58 (34)
77 (74)
1CL6
33
15
3.3
48 (45)
79 (71)
CYB5R/cyb
Microsomal
P450 Only
2IAG
4
a
The RMSIP and BC obtained from sequence-based alignment files (Clustal Omega program)
are given in parenthesis.
5
Table S4. Dynamic similarity information for CYP proteins. Each value represents the average
value from the pairwise comparisons of three proteins within each CYP class. Dynamic
similarity values in terms of BC and RMSIP are given in percentages (BC or RMSIP x 100). The
alignment files used for comparative analysis were obtained using two different multiple
sequence alignment programs - the Mustang and the Clustal Omega.
CYP Class
% Dynamic Similarity
RMSIP
Mustang
Clustal Omega
BC
Mustang
Clustal Omega
Bacterial
70 ± 5
66 ±7
83 ± 2
81 ± 2
CYB5R/cyb
65 ± 5
64 ± 8
82 ± 2
81 ± 4
Microsomal
49 ± 16
35 ± 4
80 ± 3
76 ± 4
Mitochondrial
63 ±12
54 ± 12
82 ± 3
77 ± 4
P450 Only
53 ±5
36 ± 8
79 ± 2
73 ± 2
6
Table S5. Dynamic similarity information for CYP proteins compared across various P450
systems. Each value represents the average value from all pairwise comparisons between two
CYP classes, with three proteins in each class. Thus, each value represents nine individual
pairwise comparisons. Dynamic similarity values in terms of RMSIP and BC are given in
percentages (RMSIP or BC x 100). The alignment files used for comparative analysis were
obtained using two different multiple sequence alignment programs - the Mustang and the
Clustal Omega.
CYP Classes Compared
% Dynamic similarity
RMSIP
BC
Mustang Clustal Omega
Mustang Clustal Omega
Bacterial
CYB5R/cyb
64 ± 6
59 ± 4
84 ± 1
82 ± 1
Bacterial
Microsomal
58 ± 6
58 ± 6
81 ± 3
80 ± 1
Bacterial
Mitochondrial
62 ± 3
57 ± 5
83 ± 2
79 ± 2
Bacterial
P450 Only
63 ± 14
59 ± 15
83 ± 3
81 ± 6
CYB5R/cyb
Microsomal
61 ± 12
61 ± 10
85 ± 4
83 ± 3
CYB5R/cyb
Mitochondrial
69 ± 8
62 ± 9
87 ± 2
84 ± 4
CYB5R/cyb
P450 Only
62 ± 6
57 ± 3
83 ± 1
81 ± 1
Microsomal
Mitochondrial
63 ± 11
62 ± 11
85 ± 4
83 ± 3
Microsomal
P450 Only
55 ± 8
54 ± 8
81 ± 2
79 ± 1
Mitochondrial P450 Only
59 ± 5
54 ± 6
82 ± 1
80 ± 1
7