8TVT: Cysteine desulfurase

Structure of human Cysteine desulfurase Nfs1 with L-propargylglycine bound to active site PLP in complex with ISD11, Acp1 and ISCU2. Determined by X-ray diffraction at 2.0 Å resolution. Released 11 Sept 2024.

Method: X-ray diffraction
Resolution: 2.0 Å
Organisms: Homo sapiens, Escherichia coli
Chains: 4
Atoms: 6,126
Mol. weight: 84.14 kDa
Ligands: PLP, LPH, P15, DTT
Released: 11 Sept 2024

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

Secondary structure: helices and β-sheets

8TVT contains 41 α-helices and 27 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: 24 helices, 18 β-strands

Element	Residues	Length	Sheet
α-helix	56	1
β-strand	57	1	1
α-helix	58	1
β-strand	59-60	2	2
α-helix	68-70	3
α-helix	71-82	12
α-helix	94-114	21
α-helix	118-120	3
β-strand	121-124	4	3
α-helix	127-132	6
α-helix	133-137	5
α-helix	138-141	4
β-strand	148-152	5	3
α-helix	157-168	12
β-strand	172-176	5	3
α-helix	186-192	7
β-strand	197-201	5	3
β-strand	205	1	4
β-strand	211	1	5
β-strand	212	1	4
α-helix	213	1
α-helix	215-224	10
β-strand	228-232	5	3
β-strand	251-255	5	3
α-helix	256-258	3
β-strand	266-270	5	3
α-helix	276-277	2
α-helix	288-290	3
α-helix	298-336	39
β-strand	340-342	3	6
β-strand	349	1	5
β-strand	353-358	6	6
α-helix	363-369	7
β-strand	373-374	2	2
β-strand	376	1	6
α-helix	389	1
α-helix	390-394	5
α-helix	399-402	4
β-strand	405-409	5	6
α-helix	416-435	20
α-helix	438-444	7
α-helix	449-451	3

Chain B: 5 helices, 1 β-strand

Element	Residues	Length	Sheet
α-helix	5-20	16
α-helix	26-42	17
α-helix	49-75	27
α-helix	79-80	2
β-strand	81	1	1
α-helix	82-84	3

Chain C: 5 helices, 2 β-strands

Element	Residues	Length	Sheet
α-helix	6-15	10
α-helix	19-21	3
β-strand	27	1	7
α-helix	36-50	15
α-helix	56-59	4
β-strand	64	1	7
α-helix	65-73	9

Chain D: 7 helices, 6 β-strands

Element	Residues	Length	Sheet
α-helix	37-44	8
β-strand	49	1	8
β-strand	59-66	8	8
α-helix	67-69	3
β-strand	71-79	9	8
β-strand	84	1	9
β-strand	85-93	9	8
α-helix	96-109	14
β-strand	113	1	9
α-helix	114-117	4
α-helix	122-129	8
α-helix	133-135	3
α-helix	136-157	22

Molecules and chains

Molecule	Chains	Type	Length	Organism	UniProt
Cysteine desulfurase	A	protein	403	Homo sapiens	Q9Y697 (AlphaFold model)
LYR motif-containing protein 4	B	protein	91	Homo sapiens	Q9HD34 (AlphaFold model)
Acyl carrier protein	C	protein	76	Escherichia coli	P0A6A8 (AlphaFold model)
Iron-sulfur cluster assembly enzyme ISCU	D	protein	135	Homo sapiens	Q9H1K1 (AlphaFold model)

Sequence of entity 1 (A), FASTA

>8TVT_1 Cysteine desulfurase (chains A)
MGSSLRPLYMDVQATTPLDPRVLDAMLPYLINYYGNPHSRTHAYGWESEAAMERARQQVA
SLIGADPREIIFTSGATESNNIAIKGVARFYRSRKKHLITTQTEHKCVLDSCRSLEAEGF
QVTYLPVQKSGIIDLKELEAAIQPDTSLVSVMTVNNEIGVKQPIAEIGRICSSRKVYFHT
DAAQAVGKIPLDVNDMKIDLMSISGHKIYGPKGVGAIYIRRRPRVRVEALQSGGGQERGM
RSGTVPTPLVVGLGAACEVAQQEMEYDHKRISKLSERLIQNIMKSLPDVVMNGDPKHHYP
GCINLSFAYVEGESLLMALKDVALSSGSACTSASLEPSYVLRAIGTDEDLAHSSIRFGIG
RFTTEEEVDYTVEKCIQHVKRLREMSPLWEMVQDGIDLKSIKW

Sequence of entity 2 (B), FASTA

>8TVT_2 LYR motif-containing protein 4 (chains B)
MAASSRAQVLALYRAMLRESKRFSAYNYRTYAVRRIRDAFRENKNVKDPVEIQTLVNKAK
RDLGVIRRQVHIGQLYSTDKLIIENRDMPRT

Sequence of entity 3 (C), FASTA

>8TVT_3 Acyl carrier protein (chains C)
STIEERVKKIIGEQLGVKQEEVTNNASFVEDLGADSLDTVELVMALEEEFDTEIPDEEAE
KITTVQAAIDYINGHQ

Sequence of entity 4 (D), FASTA

>8TVT_4 Iron-sulfur cluster assembly enzyme ISCU (chains D)
MAYHKKVVDHYENPRNVGSLDKTSKNVGTGLVGAPACGDVMKLQIQVDEKGKIVDARFKT
FGCGSAIASSSLATEWVKGKTVEEALTIKNTDIAKELCLPPVKLHCSMLAEDAIKAALAD
YKLKQEPKKGEAEKK

Ligands and cofactors

ID	Name	Formula	Copies
PLP	Pyridoxal-5'-phosphate	C8 H10 N O6 P	1
LPH	L-Propargylglycine	C5 H7 N O2	1
P15	2,5,8,11,14,17-hexaoxanonadecan-19-ol	C13 H28 O7	1
DTT	2,3-dihydroxy-1,4-dithiobutane	C4 H10 O2 S2	1
EDT	{[-(bis-carboxymethyl-amino)-ethyl]-carboxymethyl-amino}-acetic acid	C10 H16 N2 O8	1
8Q1	S-[2-({N-[(2R)-2-hydroxy-3,3-dimethyl-4-(phosphonooxy)butanoyl]-beta-alanyl}ami…	C23 H45 N2 O8 P S	1

Water and common crystallization additives (EDO, GOL, PEG, PG4, PGE, MES, 1PE) are not listed.

Primary citation

D-cysteine impairs tumour growth by inhibiting cysteine desulfurase NFS1. Zangari, J., Stehling, O., Freibert, S.A. et al. Nat Metab (2025). DOI 10.1038/s42255-025-01339-1 · PubMed

Other PDB entries of the same protein (UniProt Q9Y697 (AlphaFold model), which also has an AlphaFold model), best resolution first:

6UXE 1.57 Å, Structure of the human mitochondrial desulfurase complex Nfs1-ISCU2(M140I)-ISD11 with…
6W1D 1.79 Å, Structure of human mitochondrial complex Nfs1-ISCU2 (WT)-ISD11 with E.coli ACP1 at 1.8 A…
6WIH 1.9 Å, N-terminal mutation of ISCU2 (L35H36) traps Nfs1 Cys loop in the active site of ISCU2…
6WI2 1.95 Å, Structure of human mitochondrial complex Nfs1-ISCU2-ISD11 with E.coli ACP1 at 1.95 A…
8RMC 2.26 Å, Structure of the FDX2-bound core ISC complex (proximal conformation)
8RMF 2.33 Å, Structure of the core ISC complex under turnover conditions (FDX2-bound in proximal…
8RMG 2.46 Å, Structure of the core ISC complex under turnover conditions (FDX2-bound in distal…
8PK8 2.49 Å, Structure of the human mitochondrial iron-sulfur cluster biosynthesis complex during…
8RME 2.49 Å, Structure of the core ISC complex under turnover conditions (frataxin-bound)
7RTK 2.5 Å, Structure of the (NIAU)2 complex with N-terminal mutation of ISCU2 Y35D at 2.5 A…
8RMD 2.52 Å, Structure of the FDX2-bound core ISC complex (distal conformation)
8PK9 2.58 Å, Structure of the human mitochondrial iron-sulfur cluster biosynthesis complex during…

Browse structure collections

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