6LS4: A novel anti-tumor agent S-40

A novel anti-tumor agent S-40 in complex with tubulin. Determined by X-ray diffraction at 2.4 Å resolution. Released 20 Jan 2021.

Method: X-ray diffraction
Resolution: 2.4 Å
Organism: Sus scrofa
Chains: 5
Atoms: 14,402
Mol. weight: 221.76 kDa
Ligands: S40, GDP, MG, GTP
Released: 20 Jan 2021

Explore 6LS4 in 3D Show helices and sheets RCSB PDB PDBe

Secondary structure: helices and β-sheets

6LS4 contains 109 α-helices and 77 β-strands across 5 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: 26 helices, 16 β-strands

Element	Residues	Length	Sheet
β-strand	3-9	7	1
α-helix	10-27	18
α-helix	49-51	3
β-strand	53-55	3	2
β-strand	61-63	3	2
β-strand	65-69	5	1
α-helix	73-80	8
α-helix	89-91	3
β-strand	92-94	3	1
α-helix	103-104	2
α-helix	105-109	5
α-helix	111-126	16
β-strand	132-140	9	1
α-helix	144	1
α-helix	145-149	5
α-helix	150-160	11
β-strand	165-172	8	1
α-helix	173	1
α-helix	183-194	12
α-helix	195-197	3
β-strand	200-205	6	1
α-helix	206-217	12
α-helix	224-243	20
α-helix	252-259	8
β-strand	269-273	5	3
β-strand	277	1	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	325-334	10
β-strand	343	1	3
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	385-400	16
α-helix	405-409	5
α-helix	416-434	19

Chain B: 27 helices, 21 β-strands

Element	Residues	Length	Sheet
β-strand	4-9	6	5
α-helix	10-27	18
β-strand	30	1	6
β-strand	35	1	7
β-strand	36	1	6
α-helix	41-43	3
α-helix	47-49	3
β-strand	51-53	3	8
β-strand	58	1	7
β-strand	59-61	3	8
β-strand	63-67	5	5
α-helix	71-77	7
α-helix	87-89	3
β-strand	90-92	3	5
α-helix	101-102	2
α-helix	103-107	5
α-helix	108-110	3
α-helix	113-124	12
β-strand	132-138	7	5
α-helix	143-147	5
α-helix	148-158	11
β-strand	163-170	8	5
β-strand	172	1	9
β-strand	175	1	9
α-helix	181-195	15
β-strand	198-203	6	5
α-helix	204-212	9
α-helix	222-236	15
α-helix	238-241	4
α-helix	250-257	8
β-strand	265-266	2	5
β-strand	267-271	5	10
α-helix	283-285	3
α-helix	286-293	8
α-helix	296-298	3
β-strand	299	1	10
α-helix	305-307	3
β-strand	310-318	9	10
α-helix	323-336	14
α-helix	338-340	3
β-strand	341	1	10
β-strand	349-354	6	10
α-helix	357-358	2
β-strand	364-371	8	10
α-helix	372-374	3
α-helix	375-390	16
α-helix	396-399	4
α-helix	405-424	20

Chain C: 30 helices, 21 β-strands

Element	Residues	Length	Sheet
β-strand	3-9	7	11
α-helix	10-28	19
β-strand	35	1	12
α-helix	48-51	4
β-strand	53-55	3	13
β-strand	60	1	12
β-strand	61-63	3	13
β-strand	65-69	5	11
α-helix	73-80	8
α-helix	84-86	3
α-helix	89-91	3
β-strand	92-94	3	11
α-helix	103-104	2
α-helix	105-109	5
α-helix	111-113	3
α-helix	115-126	12
β-strand	132-140	9	11
α-helix	144	1
α-helix	145-149	5
α-helix	150-161	12
β-strand	165-172	8	11
α-helix	173	1
α-helix	175-177	3
α-helix	183-194	12
β-strand	200-205	6	11
α-helix	206-217	12
α-helix	224-243	20
β-strand	248	1	11
α-helix	252-259	8
β-strand	262	1	14
β-strand	265	1	14
α-helix	268	1
β-strand	269-273	5	11
β-strand	277	1	15
α-helix	285-286	2
α-helix	288-296	9
α-helix	298-300	3
β-strand	301	1	11
α-helix	307-309	3
β-strand	312-321	10	11
α-helix	325-337	13
β-strand	343	1	11
β-strand	351-356	6	11
α-helix	359-360	2
β-strand	368	1	15
α-helix	369-370	2
β-strand	373-381	9	11
α-helix	382-384	3
α-helix	385-399	15
α-helix	405-409	5
α-helix	415-434	20

Chain D: 25 helices, 17 β-strands

Element	Residues	Length	Sheet
β-strand	3-9	7	16
α-helix	10-27	18
β-strand	30	1	17
β-strand	36	1	17
α-helix	47-49	3
β-strand	51-53	3	18
β-strand	59-61	3	18
β-strand	63-67	5	16
α-helix	71-78	8
α-helix	87-89	3
β-strand	90-92	3	16
α-helix	101-105	5
α-helix	109-125	17
β-strand	130-138	9	16
α-helix	143-147	5
α-helix	148-158	11
β-strand	163-170	8	16
α-helix	181-195	15
β-strand	198-203	6	16
α-helix	204-209	6
α-helix	210-214	5
α-helix	222-236	15
α-helix	238-241	4
α-helix	250-257	8
β-strand	265-266	2	16
β-strand	267-271	5	19
α-helix	283-285	3
α-helix	286-293	8
α-helix	296-298	3
β-strand	299	1	19
α-helix	305-307	3
β-strand	310-318	9	19
α-helix	323-336	14
α-helix	338-340	3
β-strand	341	1	19
β-strand	349-354	6	19
α-helix	357-358	2
β-strand	364-371	8	19
α-helix	372-374	3
α-helix	375-390	16
α-helix	395-399	5
α-helix	405-426	22

Chain E: 1 helix, 2 β-strands

Element	Residues	Length	Sheet
β-strand	4-11	8	3
β-strand	14-22	9	3
α-helix	44-138	95

Molecules and chains

Molecule	Chains	Type	Length	Organism	UniProt
Tubulin alpha-1B chain	A, C	protein	451	Sus scrofa	Q2XVP4 (AlphaFold model)
Tubulin beta chain	B, D	protein	445	Sus scrofa	P02554 (AlphaFold model)
Stathmin	E	protein	152	Sus scrofa	A0A4X1VCH4 (AlphaFold model)

Sequence of entity 1 (A, C), FASTA

>6LS4_1 Tubulin alpha-1B chain (chains A, C)
MRECISIHVGQAGVQIGNACWELYCLEHGIQPDGQMPSDKTIGGGDDSFNTFFSETGAGK
HVPRAVFVDLEPTVIDEVRTGTYRQLFHPEQLITGKEDAANNYARGHYTIGKEIIDLVLD
RIRKLADQCTGLQGFLVFHSFGGGTGSGFTSLLMERLSVDYGKKSKLEFSIYPAPQVSTA
VVEPYNSILTTHTTLEHSDCAFMVDNEAIYDICRRNLDIERPTYTNLNRLISQIVSSITA
SLRFDGALNVDLTEFQTNLVPYPRIHFPLATYAPVISAEKAYHEQLSVAEITNACFEPAN
QMVKCDPRHGKYMACCLLYRGDVVPKDVNAAIATIKTKRSIQFVDWCPTGFKVGINYQPP
TVVPGGDLAKVQRAVCMLSNTTAIAEAWARLDHKFDLMYAKRAFVHWYVGEGMEEGEFSE
AREDMAALEKDYEEVGVDSVEGEGEEEGEEY

Sequence of entity 2 (B, D), FASTA

>6LS4_2 Tubulin beta chain (chains B, D)
MREIVHIQAGQCGNQIGAKFWEVISDEHGIDPTGSYHGDSDLQLERINVYYNEATGNKYV
PRAILVDLEPGTMDSVRSGPFGQIFRPDNFVFGQSGAGNNWAKGHYTEGAELVDSVLDVV
RKESESCDCLQGFQLTHSLGGGTGSGMGTLLISKIREEYPDRIMNTFSVMPSPKVSDTVV
EPYNATLSVHQLVENTDETYCIDNEALYDICFRTLKLTTPTYGDLNHLVSATMSGVTTCL
RFPGQLNADLRKLAVNMVPFPRLHFFMPGFAPLTSRGSQQYRALTVPELTQQMFDSKNMM
AACDPRHGRYLTVAAIFRGRMSMKEVDEQMLNVQNKNSSYFVEWIPNNVKTAVCDIPPRG
LKMSATFIGNSTAIQELFKRISEQFTAMFRRKAFLHWYTGEGMDEMEFTEAESNMNDLVS
EYQQYQDATADEQGEFEEEGEEDEA

Sequence of entity 3 (E), FASTA

>6LS4_3 Stathmin (chains E)
ADMEVIELNKCTSGQSFEVILKPPSFDGVPEFNASLPRRRDPSLEEIQKKLEAAEERRKY
QEAELLKHLAEKREHEREVIQKAIEENNNFIKMAKEKLAQKMESNKENREAHLAAMLERL
QEKDKHAEEVRKNKELKEEASRLEHHHHHHHH

Ligands and cofactors

ID	Name	Formula	Copies
S40	3-[(4-cyclopropylphenyl)sulfonylamino]-4-methyl-N-(pyridin-3-ylmethyl)benzamide	C23 H23 N3 O3 S	2
GDP	Guanosine-5'-diphosphate	C10 H15 N5 O11 P2	1
MG	Magnesium ion	Mg	6
GTP	Guanosine-5'-triphosphate	C10 H16 N5 O14 P3	3

Water and common crystallization additives (GOL, MES) are not listed.

Primary citation

A novel orally active microtubule destabilizing agent S-40 targets the colchicine-binding site and shows potent antitumor activity. Du, T., Lin, S., Ji, M. et al. Cancer Lett (2020) 495:22-32. DOI 10.1016/j.canlet.2020.08.040 · PubMed

Other PDB entries of the same protein (UniProt Q2XVP4 (AlphaFold model), which also has an AlphaFold model), best resolution first:

9U6A 1.92 Å, Tubulin-DARPin D1 in complex with a flavone
5EZY 2.05 Å, Crystal structure of T2R-TTL-taccalonolide AJ complex
5YL2 2.09 Å, Crystal structure of T2R-TTL-Y28 complex
7TTF 2.1 Å, Tubulin-RB3_SLD in complex with compound 12k
5XKG 2.2 Å, Crystal structure of T2R-TTL-CH1 complex
7L05 2.21 Å, Complex of novel maytansinoid M24 bound to T2R-TTL (two tubulin alpha/beta heterodimers,…
9M1M 2.21 Å, Cryo-EM structure of the TBC-DEC-Arl2-alpha-beta-tubulin complex with GDP-AlFx
5JQG 2.24 Å, An apo tubulin-RB-TTL complex structure used for side-by-side comparison
9M1N 2.24 Å, Cryo-EM structure of the TBC-DC-Arl2-alpha-beta-tubulin complex with GDP-AlFx
5XKH 2.25 Å, Crystal structure of T2R-TTL-CF1 complex
7TTD 2.27 Å, Tubulin-RB3_SLD in complex with compound 12e
5JCB 2.3 Å, Microtubule depolymerizing agent podophyllotoxin derivative YJTSF1

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