9D6L: Human Sec61 complex inhibited by KZR-261

Human Sec61 complex inhibited by KZR-261. Determined by electron microscopy at 3.1 Å resolution. Released 23 Jul 2025.

Method: Electron microscopy
Resolution: 3.1 Å
Organism: Homo sapiens
Chains: 3
Atoms: 4,224
Mol. weight: 70.71 kDa
Ligands: A1A2B
Released: 23 Jul 2025

Explore 9D6L in 3D Show helices and sheets RCSB PDB PDBe

Secondary structure: helices and β-sheets

9D6L contains 29 α-helices and 13 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: 26 helices, 12 β-strands

Element	Residues	Length	Sheet
α-helix	10-13	4
β-strand	19	1	1
α-helix	20-22	3
α-helix	25-27	3
α-helix	28-46	19
β-strand	49	1	2
α-helix	50	1
α-helix	59-60	2
α-helix	63-65	3
β-strand	75	1	2
α-helix	82-96	15
α-helix	108-133	26
α-helix	140-143	4
α-helix	145-168	24
α-helix	169-173	5
α-helix	178-195	18
β-strand	200	1	3
β-strand	209	1	3
α-helix	212-222	11
α-helix	226-234	9
α-helix	243-259	17
β-strand	262-265	4	4
β-strand	267-269	3	5
β-strand	276	1	5
β-strand	279-282	4	4
α-helix	289-307	19
α-helix	316-321	6
β-strand	323-324	2	6
β-strand	337-339	3	6
α-helix	340-345	6
α-helix	347-348	2
α-helix	352-354	3
α-helix	358-382	25
α-helix	387-397	11
β-strand	399-401	3	5
α-helix	409-414	6
α-helix	417-437	21
α-helix	443-466	24

Chain B: 2 helices, 0 β-strands

Element	Residues	Length	Sheet
α-helix	8-24	17
α-helix	30-65	36

Chain C: 1 helix, 1 β-strand

Element	Residues	Length	Sheet
β-strand	68	1	1
α-helix	70-94	25

Molecules and chains

Molecule	Chains	Type	Length	Organism	UniProt
Protein transport protein Sec61 subunit gamma	B	protein	68	Homo sapiens	P60059 (AlphaFold model)
Protein transport protein Sec61 subunit beta	C	protein	96	Homo sapiens	P60468 (AlphaFold model)
Protein transport protein Sec61 subunit alpha isoform 1	A	protein	476	Homo sapiens	P61619 (AlphaFold model)

Sequence of entity 1 (B), FASTA

>9D6L_1 Protein transport protein Sec61 subunit gamma (chains B)
MDQVMQFVEPSRQFVKDSIRLVKRCTKPDRKEFQKIAMATAIGFAIMGFIGFFVKLIHIP
INNIIVGG

Sequence of entity 2 (C), FASTA

>9D6L_2 Protein transport protein Sec61 subunit beta (chains C)
MPGPTPSGTNVGSSGRSPSKAVAARAAGSTVRQRKNASCGTRSAGRTTSAGTGGMWRFYT
EDSPGLKVGPVPVLVMSLLFIASVFMLHIWGKYTRS

Sequence of entity 3 (A), FASTA

>9D6L_3 Protein transport protein Sec61 subunit alpha isoform 1 (chains A)
MAIKFLEVIKPFCVILPEIQKPERKIQFKEKVLWTAITLFIFLVCCQIPLFGIMSSDSAD
PFYWMRVILASNRGTLMELGISPIVTSGLIMQLLAGAKIIEVGDTPKDRALFNGAQKLFG
MIITIGQSIVYVMTGMYGDPSEMGAGICLLITIQLFVAGLIVLLLDELLQKGYGLGSGIS
LFIATNICETIVWKAFSPTTVNTGRGMEFEGAIIALFHLLATRTDKVRALREAFYRQNLP
NLMNLIATIFVFAVVIYFQGFRYELPIRSTKVRGQIGIYPIKLFYTSNIPIILQSALVSN
LYVISQMLSARFSGNLLVSLLGTWSDTSSGGPARAYPVGGLCYYLSPPESFGSVLEDPVH
AVVYIVFMLGSCAFFSKTWIEVSGSSPRDIAKQFKDQGMVINGKRETSIYRELKKIIPTA
AAFGGLCIGALSVLADFLGAIGSGTGILLAVTIIYQYFEIFVKEQSEVGSMGALLF

Ligands and cofactors

ID	Name	Formula	Copies
A1A2B	4-{(3S)-9-(cyclohexylmethyl)-5-[(3R,5R)-4-(3-fluoro-5-methoxyphenyl)-3,5-dimeth…	C38 H61 F N6 O5 S2	1

Primary citation

Preclinical characterization of novel multi-client inhibitors of Sec61 with broad antitumor activity. Lowe, E., Anderl, J.L., Bade, D. et al. J Pharmacol Exp Ther (2025) 392:103634-103634. DOI 10.1016/j.jpet.2025.103634 · PubMed

Other PDB entries of the same protein (UniProt P60059 (AlphaFold model), which also has an AlphaFold model), best resolution first:

8DNZ 2.57 Å, Cryo-EM structure of the human Sec61 complex inhibited by apratoxin F
8DNY 2.85 Å, Cryo-EM structure of the human Sec61 complex inhibited by decatransin
8DO0 2.86 Å, Cryo-EM structure of the human Sec61 complex inhibited by mycolactone
8DO2 2.95 Å, Cryo-EM structure of the human Sec61 complex inhibited by cyclotriazadisulfonamide (CADA)
8DNX 2.98 Å, Cryo-EM structure of the human Sec61 complex inhibited by cotransin
8DO1 3.01 Å, Cryo-EM structure of the human Sec61 complex inhibited by ipomoeassin F
8DNV 3.03 Å, Cryo-EM structure of the human Sec61 complex in a partially-open apo state (Class 1)
9YWS 3.1 Å, Human Sec61 complex bound to coibamide A
9N9J 3.2 Å, Structure of a GRP94 folding intermediate engaged with a CCDC134- and FKBP11-bound…
8DO3 3.22 Å, Cryo-EM structure of the human Sec61 complex inhibited by eeyarestatin I
8OJ0 3.3 Å, 60S ribosomal subunit bound to the E3-UFM1 complex - state 2 (native)
8OJ8 3.3 Å, 60S ribosomal subunit bound to the E3-UFM1 complex - state 1 (native)

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