7O9W: Encequidar-bound human P-glycoprotein

Encequidar-bound human P-glycoprotein in complex with UIC2-Fab. Determined by electron microscopy at 3.5 Å resolution. Released 12 Jan 2022.

Method: Electron microscopy
Resolution: 3.5 Å
Organisms: Homo sapiens, Mus musculus
Chains: 3
Atoms: 12,618
Mol. weight: 191.71 kDa
Ligands: V5Q
Released: 12 Jan 2022

Explore 7O9W in 3D Show helices and sheets RCSB PDB PDBe

Secondary structure: helices and β-sheets

7O9W contains 61 α-helices and 73 β-strands across 3 chains. Residue ranges use author residue numbering, as in the PDB file, from PDBe. To see them in 3D, choose the Cartoon representation with Secondary structure coloring: helices, sheets and coils get different colors.

Chain A: 54 helices, 26 β-strands

Element	Residues	Length	Sheet
α-helix	36-39	4
α-helix	45-88	44
α-helix	106-156	51
α-helix	160-165	6
α-helix	168-173	6
α-helix	174-178	5
α-helix	179-186	8
α-helix	189-210	22
α-helix	212-237	26
α-helix	241-259	19
α-helix	263-267	5
α-helix	270-322	53
α-helix	328-347	20
α-helix	349-370	22
β-strand	392-398	7	1
β-strand	415-417	3	1
β-strand	422-426	5	2
α-helix	433-440	8
β-strand	448-453	6	1
β-strand	457	1	1
α-helix	458-460	3
α-helix	463-468	6
β-strand	470-473	4	2
β-strand	483	1	3
α-helix	484-489	6
α-helix	497-507	11
α-helix	511-515	5
β-strand	523	1	3
α-helix	526-528	3
α-helix	533-545	13
β-strand	551-555	5	2
α-helix	563-575	13
β-strand	581-585	5	2
β-strand	597-602	6	2
β-strand	605-608	4	2
α-helix	612-616	5
α-helix	621-629	9
α-helix	700-702	3
α-helix	705-707	3
α-helix	708-740	33
α-helix	745-797	53
α-helix	801-804	4
α-helix	811-853	43
α-helix	855-862	8
α-helix	865-879	15
α-helix	885-892	8
α-helix	895-902	8
α-helix	904-910	7
α-helix	913-965	53
α-helix	971-977	7
α-helix	978-982	5
α-helix	983-994	12
α-helix	996-997	2
α-helix	999-1013	15
β-strand	1026	1	4
β-strand	1035-1041	7	5
β-strand	1043	1	6
β-strand	1051	1	6
β-strand	1056-1060	5	5
β-strand	1066-1069	4	7
α-helix	1078-1083	6
β-strand	1091-1096	6	5
β-strand	1099-1100	2	5
β-strand	1104	1	4
α-helix	1106-1112	7
β-strand	1114-1116	3	7
α-helix	1127-1132	6
α-helix	1142-1151	10
α-helix	1155-1160	6
α-helix	1167-1169	3
α-helix	1171-1173	3
α-helix	1178-1190	13
β-strand	1196-1200	5	7
α-helix	1208-1221	14
β-strand	1226-1230	5	7
α-helix	1235-1238	4
β-strand	1242-1247	6	7
β-strand	1250-1253	4	7
α-helix	1257-1262	6
α-helix	1266-1271	6

Chain B: 4 helices, 25 β-strands

Element	Residues	Length	Sheet
β-strand	5-6	2	8
β-strand	10-11	2	9
β-strand	19-24	6	8
β-strand	38-43	6	9
α-helix	48-49	2
β-strand	50-53	4	9
β-strand	67-72	6	8
β-strand	75-80	6	8
β-strand	90-95	6	9
β-strand	103-104	2	9
β-strand	108-110	3	9
β-strand	120-123	4	10
α-helix	125-127	3
α-helix	128-132	5
β-strand	135-143	9	10
β-strand	145	1	11
β-strand	151	1	12
β-strand	154-156	3	13
β-strand	159-160	2	13
β-strand	167	1	10
β-strand	170	1	14
β-strand	179	1	11
β-strand	180	1	14
β-strand	182-188	7	10
α-helix	191-194	4
β-strand	197	1	15
β-strand	199-200	2	13
β-strand	203	1	12
β-strand	216	1	15

Chain C: 3 helices, 22 β-strands

Element	Residues	Length	Sheet
β-strand	3-6	4	16
β-strand	10-12	3	17
β-strand	19-25	7	16
β-strand	33-39	7	18
β-strand	45-52	8	18
β-strand	58-60	3	18
β-strand	65	1	16
β-strand	68-73	6	16
β-strand	78-83	6	16
α-helix	88-90	3
β-strand	93-99	7	18
β-strand	112	1	18
β-strand	116-117	2	18
β-strand	118-120	3	17
β-strand	131-132	2	19
β-strand	145-148	4	20
β-strand	149-150	2	19
β-strand	151-154	4	20
β-strand	163	1	21
α-helix	164-166	3
β-strand	172-180	9	20
β-strand	183-192	10	20
β-strand	203-206	4	21
β-strand	215-218	4	21
α-helix	219-222	4

Molecules and chains

Molecule	Chains	Type	Length	Organism	UniProt
Multidrug resistance protein 1	A	protein	1280	Homo sapiens	P08183 (AlphaFold model)
UIC2 Fab-fragment light chain	B	protein	220	Mus musculus
UIC2 Fab-fragment heavy chain	C	protein	225	Mus musculus

Sequence of entity 1 (A), FASTA

>7O9W_1 Multidrug resistance protein 1 (chains A)
MDLEGDRNGGAKKKNFFKLNNKSEKDKKEKKPTVSVFSMFRYSNWLDKLYMVVGTLAAII
HGAGLPLMMLVFGEMTDIFANAGNLEDLMSNITNRSDINDTGFFMNLEEDMTRYAYYYSG
IGAGVLVAAYIQVSFWCLAAGRQIHKIRKQFFHAIMRQEIGWFDVHDVGELNTRLTDDVS
KINEGIGDKIGMFFQSMATFFTGFIVGFTRGWKLTLVILAISPVLGLSAAVWAKILSSFT
DKELLAYAKAGAVAEEVLAAIRTVIAFGGQKKELERYNKNLEEAKRIGIKKAITANISIG
AAFLLIYASYALAFWYGTTLVLSGEYSIGQVLTVFFSVLIGAFSVGQASPSIEAFANARG
AAYEIFKIIDNKPSIDSYSKSGHKPDNIKGNLEFRNVHFSYPSRKEVKILKGLNLKVQSG
QTVALVGNSGCGKSTTVQLMQRLYDPTEGMVSVDGQDIRTINVRFLREIIGVVSQEPVLF
ATTIAENIRYGRENVTMDEIEKAVKEANAYDFIMKLPHKFDTLVGERGAQLSGGQKQRIA
IARALVRNPKILLLDEATSALDTESEAVVQVALDKARKGRTTIVIAHRLSTVRNADVIAG
FDDGVIVEKGNHDELMKEKGIYFKLVTMQTAGNEVELENAADESKSEIDALEMSSNDSRS
SLIRKRSTRRSVRGSQAQDRKLSTKEALDESIPPVSFWRIMKLNLTEWPYFVVGVFCAII
NGGLQPAFAIIFSKIIGVFTRIDDPETKRQNSNLFSLLFLALGIISFITFFLQGFTFGKA
GEILTKRLRYMVFRSMLRQDVSWFDDPKNTTGALTTRLANDAAQVKGAIGSRLAVITQNI
ANLGTGIIISFIYGWQLTLLLLAIVPIIAIAGVVEMKMLSGQALKDKKELEGAGKIATEA
IENFRTVVSLTQEQKFEHMYAQSLQVPYRNSLRKAHIFGITFSFTQAMMYFSYAGCFRFG
AYLVAHKLMSFEDVLLVFSAVVFGAMAVGQVSSFAPDYAKAKISAAHIIMIIEKTPLIDS
YSTEGLMPNTLEGNVTFGEVVFNYPTRPDIPVLQGLSLEVKKGQTLALVGSSGCGKSTVV
QLLERFYDPLAGKVLLDGKEIKRLNVQWLRAHLGIVSQEPILFDCSIAENIAYGDNSRVV
SQEEIVRAAKEANIHAFIESLPNKYSTKVGDKGTQLSGGQKQRIAIARALVRQPHILLLD
EATSALDTESEKVVQEALDKAREGRTCIVIAHRLSTIQNADLIVVFQNGRVKEHGTHQQL
LAQKGIYFSMVSVQAGTKRQ

Sequence of entity 2 (B), FASTA

>7O9W_2 UIC2 Fab-fragment light chain (chains B)
QVVMTQSPLSLPVSLGDQASISCRSSQSLLHSNGNTYLHWYLQKPGQSPKLLIYKVSNRF
SGVPDRFSGSGSGTDFTLKISRVEAEDLGVYFCSQSTHIPPWTFGGGTKLDIKRADAAPT
VSIFPPSSEQLTSGGLSVVCFLNNFYPKDINVKWKIDGSERQNGVLNSWTDQDSKDSTYS
MSSTLTLTKDEYERHNSYTCEATHKTSTSPIVKSFNRNEC

Sequence of entity 3 (C), FASTA

>7O9W_3 UIC2 Fab-fragment heavy chain (chains C)
EVQLQESGPELVKTGASVKISCKASGYSFSNYYIHWVKQSHGKSLEWIGFISCYNGATFY
NQKFKGKATFTVDNSSSTAYMKFNSLTFEDSAVYYCARLPIQFGNFYPMDYWGQGTTVTV
SSAKTTAPSVYPLAPVCGDTTGSSVTLGCLVKGYFPEPVTLTWNSGSLSSGVHTFPAVLQ
SDLYTLSSSVTVTSSTWPSQSITCNVAHPASSTKVDKKIEPRGPT

Ligands and cofactors

ID	Name	Formula	Copies
V5Q	~{N}-[2-[2-[4-[2-(6,7-dimethoxy-3,4-dihydro-1~{H}-isoquinolin-2-yl)ethyl]phenyl…	C38 H38 N6 O7	2

Primary citation

Discovery and Characterization of Potent Dual P-Glycoprotein and CYP3A4 Inhibitors: Design, Synthesis, Cryo-EM Analysis, and Biological Evaluations. Urgaonkar, S., Nosol, K., Said, A.M. et al. J Med Chem (2022) 65:191-216. DOI 10.1021/acs.jmedchem.1c01272 · PubMed

Other PDB entries of the same protein (UniProt P08183 (AlphaFold model), which also has an AlphaFold model), best resolution first:

8Y6H 2.49 Å, P-glycoprotein in complex with UIC2 Fab and triple elacridar molecules in LMNG detergent
8Y6I 2.54 Å, P-glycoprotein in complex with UIC2 Fab and triple elacridar molecules in nanodisc
7A69 3.2 Å, Nanodisc reconstituted human ABCB1 in complex with MRK16 Fab and vincristine
6C0V 3.4 Å, Molecular structure of human P-glycoprotein in the ATP-bound, outward-facing conformation
9CTG 3.4 Å, SapNP Reconstituted Human ABCB1 bound to ATP gammaS
7A6F 3.5 Å, Nanodisc reconstituted human ABCB1 in complex with MRK16 Fab and zosuquidar
6FN1 3.58 Å, Zosuquidar and UIC2 Fab complex of human-mouse chimeric ABCB1 (ABCB1HM)
6QEX 3.6 Å, Nanodisc reconstituted human ABCB1 in complex with UIC2 fab and taxol
7A6C 3.6 Å, Nanodisc reconstituted human ABCB1 in complex with MRK16 Fab and elacridar
7A6E 3.6 Å, Nanodisc reconstituted human ABCB1 in complex with MRK16 Fab and tariquidar
9CTC 3.6 Å, SapNP reconstituted Human ABCB1 in complex with Zosuquidar and ATP/Mg
9CR8 3.8 Å, SapNP reconstituted human ABCB1

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