Table 2

Relative MDZ metabolite formation by mutants compared with wild-type CYP3A4

	1′-OH	4-OH	1′-OH/4-OH		1′-OH	4-OH	1′-OH/4-OH
WT	100	100	1.0	WT	100	100	1.0
P107A	121	93	1.3	P107W	149	98	1.5
F108A	102	130	0.8	F108W	187	70	2.7
S119A	70	250	0.3	S119F	87	95	0.9
I120A	61	120	0.5	I120W	206	49	4.2
L210A	90	251	0.4	L210F	72	70	1.0
L211A	81	84	1.0	L211F	56	64	0.9
I301A	88	119	0.7	I301W	22	0
F304A	81	201	0.4	F304W	164	39	4.2
A305G	28	172	0.2	A305V	29	31	1.0
Y307A	16	45	0.4	Y307W	133	93	1.4
T309A	13	33	0.4	T309F	69	0
I369V	64	87	0.7	I369W	0	30	0.0
A370V	35	17	2.1	A370F	8	16	0.5
L373A	97	83	1.2	L373F	39	143	0.3
L479A	159	99	1.6	L479F	146	68	2.2

The table provides the comparison at 25 μM MDZ. For each SRS residue, one smaller and one larger substitution was considered. The wild-type CYP3A4 MDZ hydroxylation activity (6.9 and 2.2 nmol/min/nmol of P450 for 1′-OH and 4-OH MDZ, respectively) was considered 100% for each product. The relative ratio for the wild type is therefore 1.0, which is different from the actual metabolite ratio of 3.1.