8CLH: Drug cocktail

Drug cocktail (Colchicine, Epothilone A, Peloruside, Ansamitocin P3, Vinblastine) bound to tubulin (T2R-TTL) complex. Determined by X-ray diffraction at 2.5 Å resolution. Released 13 Dec 2023.

Method: X-ray diffraction
Resolution: 2.5 Å
Organisms: Bos taurus, Rattus norvegicus, Gallus gallus
Chains: 6
Atoms: 17,922
Mol. weight: 260.7 kDa
Ligands: GTP, MG, CA, GDP
Released: 13 Dec 2023

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

Secondary structure: helices and β-sheets

8CLH contains 125 α-helices and 87 β-strands across 6 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: 29 helices, 16 β-strands

Element	Residues	Length	Sheet
β-strand	4-9	6	1
α-helix	10-28	19
α-helix	48-51	4
β-strand	53-55	3	2
β-strand	61-63	3	2
β-strand	65-69	5	1
α-helix	73-78	6
α-helix	84-86	3
α-helix	89-91	3
β-strand	92-94	3	1
α-helix	103-104	2
α-helix	105-109	5
α-helix	110-127	18
β-strand	134-140	7	1
α-helix	144	1
α-helix	145-149	5
α-helix	150-160	11
β-strand	165-172	8	1
α-helix	183-194	12
α-helix	195-197	3
β-strand	200-205	6	1
α-helix	206-215	10
α-helix	224-243	20
α-helix	253-259	7
β-strand	269-273	5	3
β-strand	277	1	4
α-helix	284-287	4
α-helix	288-294	7
α-helix	298-300	3
β-strand	301	1	3
α-helix	307-309	3
β-strand	312-321	10	3
α-helix	325-337	13
α-helix	342	1
β-strand	343	1	3
α-helix	344	1
β-strand	349-356	8	3
α-helix	359-361	3
β-strand	368	1	4
α-helix	369-370	2
β-strand	373-381	9	3
α-helix	382-384	3
α-helix	385-399	15
α-helix	405-409	5
α-helix	415-435	21

Chain B: 26 helices, 18 β-strands

Element	Residues	Length	Sheet
β-strand	3-9	7	5
α-helix	10-27	18
β-strand	30	1	6
β-strand	35	1	7
β-strand	36	1	6
α-helix	49-51	3
β-strand	53-56	4	7
β-strand	60-63	4	7
β-strand	65-69	5	5
α-helix	73-79	7
α-helix	89-91	3
β-strand	92-94	3	5
α-helix	103-104	2
α-helix	105-109	5
α-helix	111-127	17
β-strand	132-140	9	5
α-helix	145-149	5
α-helix	150-160	11
β-strand	165-172	8	5
α-helix	183-197	15
β-strand	200-205	6	5
α-helix	206-211	6
α-helix	212-216	5
α-helix	224-238	15
α-helix	240-243	4
α-helix	252-259	8
β-strand	267-268	2	5
β-strand	269-273	5	8
α-helix	285-287	3
α-helix	288-296	9
α-helix	298-300	3
β-strand	301	1	8
α-helix	307-309	3
β-strand	312-321	10	8
α-helix	325-338	14
α-helix	340-342	3
β-strand	343	1	8
β-strand	351-356	6	8
α-helix	359-360	2
β-strand	373-381	9	8
α-helix	382-384	3
α-helix	385-399	15
α-helix	406-409	4
α-helix	415-436	22

Chain C: 29 helices, 14 β-strands

Element	Residues	Length	Sheet
β-strand	4-9	6	9
α-helix	10-28	19
α-helix	48-51	4
β-strand	53-55	3	10
β-strand	61-63	3	10
β-strand	65-69	5	9
α-helix	73-79	7
α-helix	84-86	3
α-helix	89-91	3
β-strand	92-94	3	9
α-helix	103-104	2
α-helix	105-109	5
α-helix	111-113	3
α-helix	115-126	12
β-strand	134-140	7	9
α-helix	144	1
α-helix	145-149	5
α-helix	150-161	12
β-strand	165-172	8	9
α-helix	183-194	12
β-strand	200-205	6	9
α-helix	206-217	12
α-helix	224-243	20
α-helix	252-259	8
α-helix	268	1
β-strand	269-273	5	11
α-helix	278-281	4
α-helix	288-294	7
α-helix	298-300	3
β-strand	301	1	11
α-helix	307-309	3
β-strand	312-321	10	11
α-helix	325-338	14
β-strand	343	1	11
β-strand	351-356	6	11
α-helix	359-360	2
α-helix	369-370	2
β-strand	373-381	9	11
α-helix	382-384	3
α-helix	385-399	15
α-helix	405-410	6
α-helix	415-435	21
α-helix	438-439	2

Chain D: 25 helices, 18 β-strands

Element	Residues	Length	Sheet
β-strand	4-9	6	12
α-helix	10-28	19
β-strand	30	1	13
β-strand	35	1	14
β-strand	36	1	13
α-helix	41-45	3
α-helix	49-51	3
β-strand	53-56	4	14
β-strand	60-63	4	14
β-strand	65-69	5	12
α-helix	72-80	9
α-helix	89-91	3
β-strand	92-94	3	12
α-helix	103-107	5
α-helix	110-127	18
β-strand	134-140	7	12
α-helix	145-149	5
α-helix	150-160	11
β-strand	165-172	8	12
α-helix	183-197	15
β-strand	200-205	6	12
α-helix	206-211	6
α-helix	212-216	5
α-helix	224-238	15
α-helix	240-243	4
α-helix	252-259	8
β-strand	267-268	2	12
β-strand	269-273	5	15
α-helix	278-282	5
α-helix	288-295	8
α-helix	298-300	3
β-strand	301	1	15
α-helix	307-309	3
β-strand	312-321	10	15
α-helix	325-338	14
α-helix	340-342	3
β-strand	343	1	15
β-strand	351-356	6	15
β-strand	373-381	9	15
α-helix	382-384	3
α-helix	385-400	16
α-helix	405-409	5
α-helix	416-437	22

Chain E: 1 helix, 2 β-strands

Element	Residues	Length	Sheet
β-strand	7-13	7	3
β-strand	17-25	9	3
α-helix	47-141	95

Chain F: 15 helices, 19 β-strands

Element	Residues	Length	Sheet
β-strand	2-6	5	16
α-helix	12-23	12
β-strand	27-29	3	16
β-strand	39-41	3	16
α-helix	49-51	3
β-strand	61-62	2	16
α-helix	69-72	4
α-helix	74-83	10
β-strand	97-100	4	17
α-helix	128-140	13
β-strand	147-151	5	17
β-strand	163	1	17
α-helix	166-175	10
β-strand	180-184	5	17
β-strand	189	1	18
β-strand	192	1	19
β-strand	197-207	11	19
β-strand	213-216	4	19
β-strand	220-227	8	19
α-helix	228	1
α-helix	258-260	3
β-strand	261-263	3	19
α-helix	264-275	12
α-helix	279	1
α-helix	280-284	5
α-helix	285-302	18
β-strand	310-311	2	16
β-strand	313-321	9	19
β-strand	322	1	18
β-strand	327-333	7	19
α-helix	340-342	3
α-helix	343-350	8
α-helix	351-355	5
β-strand	375-377	3	19

Molecules and chains

Molecule	Chains	Type	Length	Organism	UniProt
Tubulin alpha-1B chain	A, C	protein	440	Bos taurus	P81947 (AlphaFold model)
Tubulin beta-2B chain	B, D	protein	430	Bos taurus	Q6B856 (AlphaFold model)
Stathmin-4	E	protein	138	Rattus norvegicus	P63043 (AlphaFold model)
Tubulin tyrosine ligase	F	protein	381	Gallus gallus	A0A8V0Z8P0 (AlphaFold model)

Sequence of entity 1 (A, C), FASTA

>8CLH_1 Tubulin alpha-1B chain (chains A, C)
MRECISIHVGQAGVQIGNACWELYCLEHGIQPDGQMPSDKTIGGGDDSFNTFFSETGAGK
HVPRAVFVDLEPTVIDEVRTGTYRQLFHPEQLITGKEDAANNYARGHYTIGKEIIDLVLD
RIRKLADQCTGLQGFLVFHSFGGGTGSGFTSLLMERLSVDYGKKSKLEFSIYPAPQVSTA
VVEPYNSILTTHTTLEHSDCAFMVDNEAIYDICRRNLDIERPTYTNLNRLISQIVSSITA
SLRFDGALNVDLTEFQTNLVPYPRIHFPLATYAPVISAEKAYHEQLSVAEITNACFEPAN
QMVKCDPRHGKYMACCLLYRGDVVPKDVNAAIATIKTKRSIQFVDWCPTGFKVGINYQPP
TVVPGGDLAKVQRAVCMLSNTTAIAEAWARLDHKFDLMYAKRAFVHWYVGEGMEEGEFSE
AREDMAALEKDYEEVGVDSV

Sequence of entity 2 (B, D), FASTA

>8CLH_2 Tubulin beta-2B chain (chains B, D)
REIVHIQAGQCGNQIGAKFWEVISDEHGIDPTGSYHGDSDLQLERINVYYNEATGNKYVP
RAILVDLEPGTMDSVRSGPFGQIFRPDNFVFGQSGAGNNWAKGHYTEGAELVDSVLDVVR
KESESCDCLQGFQLTHSLGGGTGSGMGTLLISKIREEYPDRIMNTFSVMPSPKVSDTVVE
PYNATLSVHQLVENTDETYCIDNEALYDICFRTLKLTTPTYGDLNHLVSATMSGVTTCLR
FPGQLNADLRKLAVNMVPFPRLHFFMPGFAPLTSRGSQQYRALTVPELTQQMFDSKNMMA
ACDPRHGRYLTVAAIFRGRMSMKEVDEQMLNVQNKNSSYFVEWIPNNVKTAVCDIPPRGL
KMSATFIGNSTAIQELFKRISEQFTAMFRRKAFLHWYTGEGMDEMEFTEAESNMNDLVSE
YQQYQDATAD

Sequence of entity 3 (E), FASTA

>8CLH_3 Stathmin-4 (chains E)
MEVIELNKCTSGQSFEVILKPPSFDGVPEFNASLPRRRDPSLEEIQKKLEAAEERRKYQE
AELLKHLAEKREHEREVIQKAIEENNNFIKMAKEKLAQKMESNKENREAHLAAMLERLQE
KDKHAEEVRKNKELKEEA

Sequence of entity 4 (F), FASTA

>8CLH_4 Tubulin tyrosine ligase (chains F)
MYTFVVRDENSSVYAEVSRLLLATGQWKRLRKDNPRFNLMLGERNRLPFGRLGHEPGLVQ
LVNYYRGADKLCRKASLVKLIKTSPELSESCTWFPESYVIYPTNLKTPVAPAQNGIRHLI
NNTRTDEREVFLAAYNRRREGREGNVWIAKSSAGAKGEGILISSEASELLDFIDEQGQVH
VIQKYLEKPLLLEPGHRKFDIRSWVLVDHLYNIYLYREGVLRTSSEPYNSANFQDKTCHL
TNHCIQKEYSKNYGRYEEGNEMFFEEFNQYLMDALNTTLENSILLQIKHIIRSCLMCIEP
AISTKHLHYQSFQLFGFDFMVDEELKVWLIEVNGAPACAQKLYAELCQGIVDVAISSVFP
LADTGQKTSQPTSIFIKLHHH

Ligands and cofactors

ID	Name	Formula	Copies
GTP	Guanosine-5'-triphosphate	C10 H16 N5 O14 P3	2
MG	Magnesium ion	Mg	4
CA	Calcium ion	Ca	2
GDP	Guanosine-5'-diphosphate	C10 H15 N5 O11 P2	2
LOC	N-[(7S)-1,2,3,10-tetramethoxy-9-oxo-6,7-dihydro-5H-benzo[d]heptalen-7-yl]ethana…	C22 H25 N O6	1
EP	Epothilone a	C26 H39 N O6 S	2
POU	Peloruside A	C27 H48 O11	1
VLB	(2ALPHA,2'BETA,3BETA,4ALPHA,5BETA)-vincaleukoblastine	C46 H58 N4 O9	1
BKF	(1S,2S,3S,5S,6S,16Z,18Z,20R,21S)-11-chloro-21-hydroxy-12,20-dimethoxy-2,5,9,16-…	C32 H43 Cl N2 O9	1
ACP	Phosphomethylphosphonic acid adenylate ester	C11 H18 N5 O12 P3	1

Primary citation

A multi-reservoir extruder for time-resolved serial protein crystallography and compound screening at X-ray free-electron lasers. Wranik, M., Kepa, M.W., Beale, E.V. et al. Nat Commun (2023) 14:7956-7956. DOI 10.1038/s41467-023-43523-5 · PubMed

Other PDB entries of the same protein (UniProt P81947 (AlphaFold model), which also has an AlphaFold model), best resolution first:

6S8K 1.52 Å, Structure, Thermodynamics, and Kinetics of Plinabulin Binding to two Tubulin Isotypes
8QL2 1.7 Å, Ultrafast structural transitions in an azobenzene photoswitch at near-atomic resolution:…
6ZWB 1.75 Å, Z-SBTub3 photoswitch bound to tubulin-DARPin D1 complex
4I4T 1.8 Å, Crystal structure of tubulin-RB3-TTL-Zampanolide complex
5IYZ 1.8 Å, Tubulin-MMAE complex
5NQU 1.8 Å, Tubulin Darpin cryo structure
7YZ3 1.8 Å, Molecular snapshots of drug release from tubulin: Apo state
8QEA 1.8 Å, Ultrafast structural transitions in an azobenzene photoswitch at near-atomic resolution:…
8QL3 1.8 Å, Ultrafast structural transitions in an azobenzene photoswitch at near-atomic resolution:…
8QL4 1.8 Å, Ultrafast structural transitions in an azobenzene photoswitch at near-atomic resolution:…
8QL5 1.8 Å, Ultrafast structural transitions in an azobenzene photoswitch at near-atomic resolution:…
8QL6 1.8 Å, Ultrafast structural transitions in an azobenzene photoswitch at near-atomic resolution:…

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