Table 2.

Structural features of the CYP3A4-inhibitor complexes

compound	Fe-N bond		pyridine ring rotation (°)b	I-helix displacement (Å)c	F-F′ loop conformation	H-bonds		Boc-interacting residuesd
	distance (Å)	angle (°)a				atoms	length (Å)
5a	2.28	10	22	0.37–0.45	ordered	O12-Arg212:NH2 O13-Arg212:NH2 O12-Ala370:O O19-Ser119:OG	2.64 3.17 3.19 2.90	304, 37, 372
5b	2.26	0	30	0.58–0.70	traceable	none		215, 373, 374
5c	2.23	1	30	1.64–1.43	traceable	O22-Ser119:OG	2.75	heme, 105, 119
8a	2.21	13	2	0.54–0.63	ordered	O19-Ala370:O O26-Ser119:OG	3.13 2.45	217, 370, 372, 374
8b	2.22	2	30	1.56–1.65	traceable	none		212, 213, 304
8c	2.37	5	25	1.95–1.94	disordered	O22-Ser119:OG	2.73	304, 369, 482
8d Ae	2.27	13	7	0.50–0.63	ordered	O29 – Ser119:OG N13-Arg372:O	2.37 2.70	212, 309, 369, 370
Be	2.30	10	7	0.50–0.63	ordered	O29 – Ser119:OG N13-Arg372:O	2.28 2.70	212, 309, 369, 370
8e	2.37	25	5	0.54–0.68	traceable	O21 – Ser119:OG N33-Arg372:O	2.47 3.20	212, 309, 369, 370
8f	2.21	4	30	1.81–2.40	disordered	O22 – Ser119:OG	2.53	106. 108, 115, 119, 120
ritonavirf	2.16	8	45g	1.99–2.18	traceable	O24: Ser119:OG O41: Ser119:OG	2.92 2.84

^aDeviation from perpendicularity.

^bAngle between the planes passing through the pyridine ring and the NB-ND heme atoms

^cDistance between the C_α-atoms of Phe304 and Ala305 in the inhibitor-bound and the ligand-free CYP3A4 structure (PDB ID 5VCC).

^dResidues within the Van der Waals distance from the terminal Boc group.

^eTwo alternative conformation with the occupancy of 60 and 40%, respectively.

^fParameters derived from the 5VC0 structure.

^gRespective angle for the thiazole ring.