CYP1A2

CSM

Region

Function

Reference

E163K, K170Q

6-7, 7

D helix

Enhanced activity
Substrate selectivity

25-28

V193M

8-9

E helix

E225N

10

F helix

 

Q258H

11

G helix

G437D

18

K’-L loop

CYP2A6

 

S183C

7-8

E helix

Enhanced activity
Altered substrate specificity
Novel activity

29-32

L206Q, F209I

8-9

F helix

S224P

9

F-G loop

L240C

10-11

G helix

Y287H

11-12

I helix

N297Q, I300V, T305S

12

I helix

CYP2Bs

 

V183L

7-8

E helix

Enhanced activity
Altered substrate specificity
Increased protein stability
Enhanced tolerance to organic solvents

33-37

F202A, L209A

8-9

F helix

K236I

10-11

G helix

D257N

10-11

G-H loop

L264F

11

H helix

L295H

12

I helix

S334P, P334S

13-14

J-J’ loop

CYP3A4

 

L216W

8

F helix

Enhanced activity
Altered substrate specificity

38

F228I

10

F-G loop

 

T433S

17

L-helix

 

The location of the region is based on CYP X-ray structures and/or models of individual enzyme, except for CYP2Bs, in which CYP2B4 was used to identify regions. The CSM number is based on the CSM analysis of CYP2 family performed earlier (22). The information on functional characterizations of the mutants are based on earlier studies (last column) using rational and random mutagenesis approaches. Note that the regions for the same/similar residue numbers in different families (e.g. 1 vs. 2) vary more than the regions for the same/similar residue numbers within the same families or between different subfamilies (e.g. 2A vs. 2B). Represents between the two CSM or regions; e.g. 8-9 means between CSM 8 and 9.
Table 1: Analysis of CYP mutants, locations, and functional characterizations.