TABLE 3.

Transmembrane localization of P-gp residues involved in substrate recognition

P-gp residues identified from point mutagenesis, chemical labeling (10, 57), or crystallographic data (22). The equivalent residues belonging to MsbA, Sav1866, and SUR1 are identified thanks to the primary sequences alignment represented in supplemental Fig. S2.

	P-gp	MsbA	SUR1	Sav1866	References
N-terminal
TM1	His61	Ile28	Gly16	Phe17	10
	Gly64	Gly31	Cys19	Ile20	10
	Leu65	Ile32	Ile20	Ile21	10
	Met69	Leu36	Val24	Ile25	22
TM4	Ser222	Ala175	Ile467	Phe171	22
TM5	Leu304	Leu257	Ala549	Thr253	22
	Ile306	Ala259	Pro551	Thr255	10
	Tyr307	Ser260	Ile552	Asp256	22
TM6	Phe335	Phe288	Leu580	Val284	10
	Phe336	Ser289	Ser581	Gly285	22
	Val338	Met291	Phe583	Leu287	10
	Leu339	Ile292	His584	Glu288	22
	Ile340	Ala293	Ile585	Leu289	22
	Gly341	Leu294	Leu586	Leu290	10
	Ala342	Met295	Val587	Phe291	22
	Phe343	Arg296	Thr588	Gly292	22
	Ala354	Gln307	Ser599	Thr303	10
C-terminal
TM7	Gln725	Asn37	Leu1028	Pro34	57
	Pro726	Ala38	Val1027	Leu35	57
	Phe728	Ser40	Ile1031	Ile37	57
	Ala729	Asp41	Asp1030	Lys38	57
	Phe732	Met44	Leu1035	Ile41	22
TM8	Leu762	Leu54	Leu1070	Phe70	22
TM9	Thr837	Val147	Ser1143	Trp141	22
	Ala841	Ala151	Leu1147	Ile145	10
	Leu843	Ile153	Cys1149	Ile147	10
TM10	Pro866	Pro176	Ile1172	Pro172	10
	Ile868	Val178	Cys1174	Tyr174	22
	Ala869	Ser179	Tyr1175	Ile175	10
	Gly872	Ile182	Gln1178	Val178	22
TM11	Ile937	Ala247	Ala1243	Trp243	10
	Phe938	Ser248	Asn1244	Asn244	10
	Phe942	Asp252	Glu1248	Phe248	10
	Ser943	Pro253	Val1249	Ala249	10
	Thr945	Ile255	Met1251	Phe251	10
	Gln946	Gln256	Glu1252	Asn252	10
	Tyr950	Ser260	Ala1256	Asp256	10
	Ser952	Ala262	Val1258	Gly258	10
	Tyr953	Leu263	Val1259	Pro259	10
	Phe957	Leu267	Ala1263	Ile263	10
TM12	Leu975	Thr285	Gly1281	Ala281	10
	Phe978	Phe288	Leu1284	Val284	10
	Ser979	Ser289	Thr1285	Gly285	22
	Val981	Met291	Ala1287	Leu287	10
	Val982	Ile292	Leu1288	Glu288	10
	Phe983	Ala293	Met1289	Leu289	10
	Gly984	Leu294	Val1290	Leu290	22
	Ala985	Met295	Ser1291	Phe291	22
	Met986	Arg296	Asn1292	Gly292	22
	Gly989	Lys299	Asn1295	Arg295	22
	Gln990	Ser300	Trp1296	Arg296	22
	Ser993	Asn303	Arg1299	Ala299	22