8ERA: RMC-5552

RMC-5552 in complex with mTORC1 and FKBP12. Determined by electron microscopy at 2.86 Å resolution. Released 28 Dec 2022.

Method: Electron microscopy
Resolution: 2.86 Å
Organism: Homo sapiens
Chains: 4
Atoms: 29,054
Mol. weight: 487.69 kDa
Ligands: XYU, XZ9
Released: 28 Dec 2022

Explore 8ERA in 3D Show helices and sheets RCSB PDB PDBe

Secondary structure: helices and β-sheets

8ERA contains 196 α-helices and 89 β-strands across 4 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: 141 helices, 12 β-strands

Element	Residues	Length	Sheet
α-helix	19-29	11
α-helix	38-52	15
α-helix	61-73	13
α-helix	83-93	11
α-helix	102-114	13
α-helix	123-134	12
α-helix	141-155	15
α-helix	165-178	14
α-helix	180-183	4
α-helix	188-197	10
α-helix	204-222	19
α-helix	234-245	12
α-helix	259-275	17
α-helix	277-288	12
α-helix	357-360	4
α-helix	362-375	14
α-helix	387-402	16
α-helix	413-424	12
α-helix	427-443	17
α-helix	449-451	3
α-helix	452-462	11
α-helix	479-490	12
α-helix	499-510	12
α-helix	517-527	11
α-helix	533-548	16
α-helix	580-588	9
α-helix	601-611	11
α-helix	616-629	14
α-helix	649-665	17
α-helix	670-677	8
α-helix	690-699	10
α-helix	706-717	12
α-helix	723-742	20
α-helix	749-762	14
α-helix	765-767	3
α-helix	769-771	3
α-helix	772-783	12
α-helix	792-808	17
α-helix	817-828	12
α-helix	831-833	3
α-helix	838-847	10
α-helix	848-852	5
α-helix	856-860	5
α-helix	864-870	7
α-helix	871-873	3
α-helix	878-891	14
α-helix	896-902	7
α-helix	934-937	4
α-helix	943-958	16
α-helix	964-982	19
α-helix	986-989	4
α-helix	990-1002	13
α-helix	1009-1023	15
α-helix	1024-1030	7
α-helix	1031-1040	10
α-helix	1046-1062	17
α-helix	1065-1069	5
α-helix	1071-1083	13
α-helix	1091-1103	13
α-helix	1111-1123	13
α-helix	1129-1142	14
α-helix	1153-1163	11
α-helix	1170-1182	13
α-helix	1185-1191	7
α-helix	1192-1202	11
α-helix	1207-1218	12
α-helix	1263-1269	7
α-helix	1277-1293	17
α-helix	1298-1301	4
α-helix	1304-1309	6
α-helix	1318-1328	11
α-helix	1331-1347	17
α-helix	1351-1366	16
α-helix	1380-1390	11
α-helix	1393-1406	14
α-helix	1410-1422	13
α-helix	1426-1439	14
α-helix	1447-1452	6
α-helix	1456-1469	14
α-helix	1474-1487	14
α-helix	1490-1499	10
α-helix	1506-1523	18
α-helix	1526-1533	8
α-helix	1541-1553	13
α-helix	1557-1579	23
α-helix	1584-1586	3
α-helix	1587-1602	16
α-helix	1609-1611	3
α-helix	1612-1623	12
α-helix	1630-1640	11
α-helix	1646-1648	3
α-helix	1650-1662	13
α-helix	1666-1677	12
α-helix	1688-1690	3
α-helix	1694-1706	13
α-helix	1710-1730	21
α-helix	1737-1758	22
α-helix	1769-1782	14
α-helix	1787-1808	22
α-helix	1809-1813	5
α-helix	1868-1877	10
α-helix	1881-1893	13
α-helix	1900-1913	14
α-helix	1917-1929	13
α-helix	1933-1935	3
α-helix	1939-1942	4
α-helix	1943-1945	3
α-helix	1951-1966	16
α-helix	1973-1980	8
α-helix	1985-1999	15
α-helix	2005-2019	15
α-helix	2023-2035	13
α-helix	2036-2040	5
α-helix	2041	1
α-helix	2044-2059	16
α-helix	2065-2091	27
α-helix	2094-2114	21
α-helix	2115-2117	3
β-strand	2120-2122	3	1
α-helix	2123-2126	4
α-helix	2128-2132	5
α-helix	2138	1
β-strand	2139	1	2
α-helix	2140	1
α-helix	2149-2150	2
β-strand	2152	1	2
β-strand	2153-2156	4	1
β-strand	2159-2162	4	1
α-helix	2163	1
β-strand	2170-2176	7	1
β-strand	2181-2187	7	1
α-helix	2194-2210	17
α-helix	2213-2216	4
β-strand	2227-2229	3	1
β-strand	2235-2238	4	1
α-helix	2239-2240	2
β-strand	2243-2245	3	3
α-helix	2246-2256	11
α-helix	2263-2271	9
α-helix	2280-2292	13
α-helix	2298-2305	8
α-helix	2311-2334	24
α-helix	2341-2343	3
β-strand	2344-2347	4	3
β-strand	2353-2355	3	3
α-helix	2381-2385	5
α-helix	2395-2409	15
α-helix	2411-2422	12
α-helix	2429-2432	4
α-helix	2493-2509	17
α-helix	2521-2532	12
α-helix	2535-2539	5
α-helix	2543-2545	3

Chain B: 7 helices, 8 β-strands

Element	Residues	Length	Sheet
β-strand	3-9	7	4
α-helix	16-18	3
β-strand	22-31	10	4
β-strand	36-39	4	4
α-helix	40-43	4
α-helix	46	1
β-strand	47-50	4	4
α-helix	58-63	6
α-helix	64-66	3
α-helix	67-68	2
β-strand	72-77	6	4
α-helix	79-81	3
β-strand	88	1	5
β-strand	92	1	5
β-strand	98-107	10	4

Chain C: 0 helices, 31 β-strands

Element	Residues	Length	Sheet
β-strand	13-19	7	6
β-strand	23-27	5	6
β-strand	34-39	6	6
β-strand	47-50	4	7
β-strand	57-60	4	7
β-strand	62-68	7	7
β-strand	79-87	9	7
β-strand	88	1	8
β-strand	99-103	5	9
β-strand	104	1	8
β-strand	108-113	6	9
β-strand	123-126	4	9
β-strand	131-136	6	10
β-strand	142-147	6	10
β-strand	152-156	5	10
β-strand	162-165	4	10
β-strand	173-178	6	11
β-strand	184-189	6	11
β-strand	194-198	5	11
β-strand	211-216	6	11
β-strand	226-228	3	12
β-strand	234-237	4	12
β-strand	243-248	6	12
β-strand	253-259	7	12
β-strand	273	1	13
β-strand	277-278	2	14
β-strand	284-288	5	14
β-strand	289	1	13
β-strand	293-298	6	14
β-strand	304-309	6	14
β-strand	315-322	8	6

Chain Y: 48 helices, 38 β-strands

Element	Residues	Length	Sheet
α-helix	19-25	7
α-helix	33-36	4
α-helix	41-44	4
β-strand	57-64	8	15
β-strand	85	1	16
β-strand	88	1	16
α-helix	90-92	3
α-helix	95-111	17
β-strand	118-123	6	15
α-helix	127-141	15
β-strand	145-151	7	15
α-helix	156-158	3
β-strand	163-167	5	17
β-strand	174-178	5	17
α-helix	179-185	7
β-strand	190-195	6	15
α-helix	200-215	16
α-helix	237-239	3
β-strand	240-244	5	15
α-helix	262-268	7
α-helix	270-278	9
α-helix	282-286	5
α-helix	292-296	5
α-helix	308-327	20
α-helix	330-337	8
α-helix	341-358	18
β-strand	365-366	2	15
α-helix	378-389	12
α-helix	390-392	3
α-helix	393-398	6
α-helix	401-406	6
α-helix	408-422	15
α-helix	429-430	2
α-helix	433-437	5
α-helix	446-457	12
α-helix	461-469	9
α-helix	473-479	7
α-helix	488-501	14
α-helix	506-511	6
α-helix	515-522	8
α-helix	529-543	15
α-helix	547-555	9
α-helix	558-564	7
α-helix	571-584	14
α-helix	589-597	9
α-helix	601-604	4
α-helix	605-609	5
α-helix	613-628	16
α-helix	635-644	10
α-helix	645-653	9
α-helix	657-671	15
α-helix	675-685	11
α-helix	807-819	13
α-helix	824-838	15
α-helix	959-964	6
α-helix	965-968	4
α-helix	976-978	3
α-helix	983-1007	25
β-strand	1015-1021	7	18
β-strand	1028-1031	4	19
β-strand	1038-1041	4	19
β-strand	1045-1050	6	19
β-strand	1055-1061	7	19
β-strand	1070-1076	7	20
β-strand	1083-1088	6	20
β-strand	1092-1097	6	20
β-strand	1107-1113	7	20
β-strand	1127-1132	6	21
β-strand	1137-1142	6	21
β-strand	1146-1150	5	21
β-strand	1157-1162	6	21
β-strand	1169-1174	6	22
β-strand	1180-1185	6	22
β-strand	1190-1194	5	22
β-strand	1203-1207	5	22
β-strand	1214-1220	7	23
β-strand	1226-1231	6	23
β-strand	1236-1239	4	23
β-strand	1246-1250	5	23
β-strand	1259-1261	3	24
β-strand	1268-1271	4	24
β-strand	1276-1280	5	24
β-strand	1286-1291	6	24
β-strand	1304-1309	6	18
β-strand	1316-1320	5	18
β-strand	1324-1329	6	18

Molecules and chains

Molecule	Chains	Type	Length	Organism	UniProt
Serine/threonine-protein kinase mTOR	A	protein	2549	Homo sapiens	P42345 (AlphaFold model)
Peptidyl-prolyl cis-trans isomerase FKBP1A	B	protein	108	Homo sapiens	P62942 (AlphaFold model)
Target of rapamycin complex subunit LST8	C	protein	326	Homo sapiens	Q9BVC4 (AlphaFold model)
Regulatory-associated protein of mTOR	Y	protein	1335	Homo sapiens	Q8N122 (AlphaFold model)

Sequence of entity 1 (A), FASTA

>8ERA_1 Serine/threonine-protein kinase mTOR (chains A)
MLGTGPAAATTAATTSSNVSVLQQFASGLKSRNEETRAKAAKELQHYVTMELREMSQEES
TRFYDQLNHHIFELVSSSDANERKGGILAIASLIGVEGGNATRIGRFANYLRNLLPSNDP
VVMEMASKAIGRLAMAGDTFTAEYVEFEVKRALEWLGADRNEGRRHAAVLVLRELAISVP
TFFFQQVQPFFDNIFVAVWDPKQAIREGAVAALRACLILTTQREPKEMQKPQWYRHTFEE
AEKGFDETLAKEKGMNRDDRIHGALLILNELVRISSMEGERLREEMEEITQQQLVHDKYC
KDLMGFGTKPRHITPFTSFQAVQPQQSNALVGLLGYSSHQGLMGFGTSPSPAKSTLVESR
CCRDLMEEKFDQVCQWVLKCRNSKNSLIQMTILNLLPRLAAFRPSAFTDTQYLQDTMNHV
LSCVKKEKERTAAFQALGLLSVAVRSEFKVYLPRVLDIIRAALPPKDFAHKRQKAMQVDA
TVFTCISMLARAMGPGIQQDIKELLEPMLAVGLSPALTAVLYDLSRQIPQLKKDIQDGLL
KMLSLVLMHKPLRHPGMPKGLAHQLASPGLTTLPEASDVGSITLALRTLGSFEFEGHSLT
QFVRHCADHFLNSEHKEIRMEAARTCSRLLTPSIHLISGHAHVVSQTAVQVVADVLSKLL
VVGITDPDPDIRYCVLASLDERFDAHLAQAENLQALFVALNDQVFEIRELAICTVGRLSS
MNPAFVMPFLRKMLIQILTELEHSGIGRIKEQSARMLGHLVSNAPRLIRPYMEPILKALI
LKLKDPDPDPNPGVINNVLATIGELAQVSGLEMRKWVDELFIIIMDMLQDSSLLAKRQVA
LWTLGQLVASTGYVVEPYRKYPTLLEVLLNFLKTEQNQGTRREAIRVLGLLGALDPYKHK
VNIGMIDQSRDASAVSLSESKSSQDSSDYSTSEMLVNMGNLPLDEFYPAVSMVALMRIFR
DQSLSHHHTMVVQAITFIFKSLGLKCVQFLPQVMPTFLNVIRVCDGAIREFLFQQLGMLV
SFVKSHIRPYMDEIVTLMREFWVMNTSIQSTIILLIEQIVVALGGEFKLYLPQLIPHMLR
VFMHDNSPGRIVSIKLLAAIQLFGANLDDYLHLLLPPIVKLFDAPEAPLPSRKAALETVD
RLTESLDFTDYASRIIHPIVRTLDQSPELRSTAMDTLSSLVFQLGKKYQIFIPMVNKVLV
RHRINHQRYDVLICRIVKGYTLADEEEDPLIYQHRMLRSGQGDALASGPVETGPMKKLHV
STINLQKAWGAARRVSKDDWLEWLRRLSLELLKDSSSPSLRSCWALAQAYNPMARDLFNA
AFVSCWSELNEDQQDELIRSIELALTSQDIAEVTQTLLNLAEFMEHSDKGPLPLRDDNGI
VLLGERAAKCRAYAKALHYKELEFQKGPTPAILESLISINNKLQQPEAAAGVLEYAMKHF
GELEIQATWYEKLHEWEDALVAYDKKMDTNKDDPELMLGRMRCLEALGEWGQLHQQCCEK
WTLVNDETQAKMARMAAAAAWGLGQWDSMEEYTCMIPRDTHDGAFYRAVLALHQDLFSLA
QQCIDKARDLLDAELTAMAGESYSRAYGAMVSCHMLSELEEVIQYKLVPERREIIRQIWW
ERLQGCQRIVEDWQKILMVRSLVVSPHEDMRTWLKYASLCGKSGRLALAHKTLVLLLGVD
PSRQLDHPLPTVHPQVTYAYMKNMWKSARKIDAFQHMQHFVQTMQQQAQHAIATEDQQHK
QELHKLMARCFLKLGEWQLNLQGINESTIPKVLQYYSAATEHDRSWYKAWHAWAVMNFEA
VLHYKHQNQARDEKKKLRHASGANITNATTAATTAATATTTASTEGSNSESEAESTENSP
TPSPLQKKVTEDLSKTLLMYTVPAVQGFFRSISLSRGNNLQDTLRVLTLWFDYGHWPDVN
EALVEGVKAIQIDTWLQVIPQLIARIDTPRPLVGRLIHQLLTDIGRYHPQALIYPLTVAS
KSTTTARHNAANKILKNMCEHSNTLVQQAMMVSEELIRVAILWHEMWHEGLEEASRLYFG
ERNVKGMFEVLEPLHAMMERGPQTLKETSFNQAYGRDLMEAQEWCRKYMKSGNVKDLTQA
WDLYYHVFRRISKQLPQLTSLELQYVSPKLLMCRDLELAVPGTYDPNQPIIRIQSIAPSL
QVITSKQRPRKLTLMGSNGHEFVFLLKGHEDLRQDERVMQLFGLVNTLLANDPTSLRKNL
SIQRYAVIPLSTNSGLIGWVPHCDTLHALIRDYREKKKILLNIEHRIMLRMAPDYDHLTL
MQKVEVFEHAVNNTAGDDLAKLLWLKSPSSEVWFDRRTNYTRSLAVMSMVGYILGLGDRH
PSNLMLDRLSGKILHIDFGDCFEVAMTREKFPEKIPFRLTRMLTNAMEVTGLDGNYRITC
HTVMEVLREHKDSVMAVLEAFVYDPLLNWRLMDTNTKGNKRSRTRTDSYSAGQSVEILDG
VELGEPAHKKTGTTVPESIHSFIGDGLVKPEALNKKAIQIINRVRDKLTGRDFSHDDTLD
VPTQVELLIKQATSHENLCQCYIGWCPFW

Sequence of entity 2 (B), FASTA

>8ERA_2 Peptidyl-prolyl cis-trans isomerase FKBP1A (chains B)
SGVQVETISPGDGRTFPKRGQTCVVHYTGMLEDGKKFDSSRDRNKPFKFMLGKQEVIRGW
EEGVAQMSVGQRAKLTISPDYAYGATGHPGIIPPHATLVFDVELLKLE

Sequence of entity 3 (C), FASTA

>8ERA_3 Target of rapamycin complex subunit LST8 (chains C)
MNTSPGTVGSDPVILATAGYDHTVRFWQAHSGICTRTVQHQDSQVNALEVTPDRSMIAAA
GYQHIRMYDLNSNNPNPIISYDGVNKNIASVGFHEDGRWMYTGGEDCTARIWDLRSRNLQ
CQRIFQVNAPINCVCLHPNQAELIVGDQSGAIHIWDLKTDHNEQLIPEPEVSITSAHIDP
DASYMAAVNSTGNCYVWNLTGGIGDEVTQLIPKTKIPAHTRYALQCRFSPDSTLLATCSA
DQTCKIWRTSNFSLMTELSIKSGNPGESSRGWMWGCAFSGDSQYIVTASSDNLARLWCVE
TGEIKREYGGHQKAVVCLAFNDSVLG

Sequence of entity 4 (Y), FASTA

>8ERA_4 Regulatory-associated protein of mTOR (chains Y)
MESEMLQSPLLGLGEEDEADLTDWNLPLAFMKKRHCEKIEGSKSLAQSWRMKDRMKTVSV
ALVLCLNVGVDPPDVVKTTPCARLECWIDPLSMGPQKALETIGANLQKQYENWQPRARYK
QSLDPTVDEVKKLCTSLRRNAKEERVLFHYNGHGVPRPTVNGEVWVFNKNYTQYIPLSIY
DLQTWMGSPSIFVYDCSNAGLIVKSFKQFALQREQELEVAAINPNHPLAQMPLPPSMKNC
IQLAACEATELLPMIPDLPADLFTSCLTTPIKIALRWFCMQKCVSLVPGVTLDLIEKIPG
RLNDRRTPLGELNWIFTAITDTIAWNVLPRDLFQKLFRQDLLVASLFRNFLLAERIMRSY
NCTPVSSPRLPPTYMHAMWQAWDLAVDICLSQLPTIIEEGTAFRHSPFFAEQLTAFQVWL
TMGVENRNPPEQLPIVLQVLLSQVHRLRALDLLGRFLDLGPWAVSLALSVGIFPYVLKLL
QSSARELRPLLVFIWAKILAVDSSCQADLVKDNGHKYFLSVLADPYMPAEHRTMTAFILA
VIVNSYHTGQEACLQGNLIAICLEQLNDPHPLLRQWVAICLGRIWQNFDSARWCGVRDSA
HEKLYSLLSDPIPEVRCAAVFALGTFVGNSAERTDHSTTIDHNVAMMLAQLVSDGSPMVR
KELVVALSHLVVQYESNFCTVALQFIEEEKNYALPSPATTEGGSLTPVRDSPCTPRLRSV
SSYGNIRAVATARSLNKSLQNLSLTEESGGAVAFSPGNLSTSSSASSTLGSPENEEHILS
FETIDKMRRASSYSSLNSLIGVSFNSVYTQIWRVLLHLAADPYPEVSDVAMKVLNSIAYK
ATVNARPQRVLDTSSLTQSAPASPTNKGVHIHQAGGSPPASSTSSSSLTNDVAKQPVSRD
LPSGRPGTTGPAGAQYTPHSHQFPRTRKMFDKGPEQTADDADDAAGHKSFISATVQTGFC
DWSARYFAQPVMKIPEEHDLESQIRKEREWRFLRNSRVRRQAQQVIQKGITRLDDQIFLN
RNPGVPSVVKFHPFTPCIAVADKDSICFWDWEKGEKLDYFHNGNPRYTRVTAMEYLNGQD
CSLLLTATDDGAIRVWKNFADLEKNPEMVTAWQGLSDMLPTTRGAGMVVDWEQETGLLMS
SGDVRIVRIWDTDREMKVQDIPTGADSCVTSLSCDSHRSLIVAGLGDGSIRVYDRRMALS
ECRVMTYREHTAWVVKASLQKRPDGHIVSVSVNGDVRIFDPRMPESVNVLQIVKGLTALD
IHPQADLIACGSVNQFTAIYNSSGELINNIKYYDGFMGQRVGAISCLAFHPHWPHLAVGS
NDYYISVYSVEKRVR

Ligands and cofactors

ID	Name	Formula	Copies
XYU	(3S,5R,6R,7E,9R,10R,12R,14S,15E,17E,19E,21S,23S,26R,27R,30R,34aS)-5,9,27-trihyd…	C51 H81 N O13	1
XZ9	1-[6-{[(3M)-4-amino-3-(2-amino-1,3-benzoxazol-5-yl)-1H-pyrazolo[3,4-d]pyrimidin…	C25 H24 N8 O3	1

Primary citation

Discovery of RMC-5552, a Selective Bi-Steric Inhibitor of mTORC1, for the Treatment of mTORC1-Activated Tumors. Burnett, G.L., Yang, Y.C., Aggen, J.B. et al. J Med Chem (2023) 66:149-169. DOI 10.1021/acs.jmedchem.2c01658 · PubMed

Other PDB entries of the same protein (UniProt P42345 (AlphaFold model), which also has an AlphaFold model), best resolution first:

4DRI 1.45 Å, Co-crystal structure of the PPIase domain of FKBP51, Rapamycin and the FRB fragment of…
9DBO 1.55 Å, Crystal structure of a synthetic Fab (R3E9) in complex with the FRB domain of mTOR
5GPG 1.67 Å, Co-crystal structure of the FK506 binding domain of human FKBP25, Rapamycin and the FRB…
5WBH 1.75 Å, Structure of the FRB domain of mTOR bound to a substrate recruitment peptide of S6K1
4DRJ 1.8 Å, o-crystal structure of the PPIase domain of FKBP52, Rapamycin and the FRB fragment of mTOR
3FAP 1.85 Å, Atomic structures of the rapamycin analogs in complex with both human FKBP12 and frb…
8PPZ 1.85 Å, Co-crystal structure of FKBP12, compound 7 and the FRB fragment of mTOR
8XI9 1.85 Å, Crystal structure of FRB-FKBP fusion protein in complex with rapamycin
9PIW 1.9 Å, Crystal structure of a synthetic Fab (1A) in complex with the FRB domain of mTOR
9DL0 2.0 Å, Crystal structure of a synthetic Fab (R3H8) in complex with the FRB domain of mTOR
9PJ1 2.05 Å, Crystal structure of a synthetic Fab (4R) in complex with the ternary assembly of…
9PIU 2.18 Å, Crystal structure of a synthetic Fab (2C) in complex with the FRB domain of mTOR

Browse structure collections

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