4x2t

X-ray crystal structure of the orally available aminopeptidase inhibitor, Tosedostat, bound to the M17 Leucyl Aminopeptidase from P. falciparum

Method: X-RAY DIFFRACTION

▼

1. Protein Identity and Related Structures Protein Identity & Related Structures

M17 leucyl aminopeptidase

Plasmodium falciparum (isolate 3D7)

State in the Current Structure

Assembly	Physical composition	Protein state	Molecular copy count	Associated components	Data consistency
1	Protein homooligomer	Homooligomer	Protein 6	ZINC ION × 12 (2S)-({(2R)-2-[(1S)-1-hydroxy-2-(hydroxyamino)-2-oxoethyl]-4-methylpentanoyl}amino)(phenyl)ethanoic acid × 5 CARBONATE ION × 6 SULFATE ION × 8 PENTAETHYLENE GLYCOL × 7 water × 6	Consistent with protein count
2	Protein homooligomer	Homooligomer	Protein 6	ZINC ION × 12 (2S)-({(2R)-2-[(1S)-1-hydroxy-2-(hydroxyamino)-2-oxoethyl]-4-methylpentanoyl}amino)(phenyl)ethanoic acid × 6 CARBONATE ION × 6 SULFATE ION × 5 PENTAETHYLENE GLYCOL × 3 water × 6	Consistent with protein count

Other States of the Same Protein in the Database

View Construct and Data Evidence

UniProt name	Q8IL11_PLAF7
Isoform	—
PDB entities	1
Chains and sequence ranges	Author chain A； PDBConstruct 1–519； UniProt 85–603 Author chain B； PDBConstruct 1–519； UniProt 85–603 Author chain C； PDBConstruct 1–519； UniProt 85–603 Author chain D； PDBConstruct 1–519； UniProt 85–603 Author chain E； PDBConstruct 1–519； UniProt 85–603 Author chain F； PDBConstruct 1–519； UniProt 85–603 Author chain G； PDBConstruct 1–519； UniProt 85–603 Author chain H； PDBConstruct 1–519； UniProt 85–603 Author chain I； PDBConstruct 1–519； UniProt 85–603 Author chain J； PDBConstruct 1–519； UniProt 85–603 Author chain K； PDBConstruct 1–519； UniProt 85–603 Author chain L； PDBConstruct 1–519； UniProt 85–603

The page prioritizes protein identity, the current assembly, associated components, oligomeric state and cross-PDB links. Chain mapping and sequence ranges are retained as data evidence. Internal IDs, import timestamps and assembly operation expressions are maintenance fields and are not shown here.

▼

2. Structure Basics 2. Structure Basics

Entry ID entry_id	4x2t
Deposition date deposition_date	2014-11-27
Structure title title	X-ray crystal structure of the orally available aminopeptidase inhibitor, Tosedostat, bound to the M17 Leucyl Aminopeptidase from P. falciparum
Keywords keywords	;M17 LEUCYL-AMINOPEPTIDASE, PROTEASE, INHIBITOR, TOSEDOSTAT, ANTIMALARIAL, PLASMODIUM FALCIPARUM, Hydrolase-Hydrolase Inhibitor complex ;; Hydrolase/Hydrolase Inhibitor
Experimental Method method	X-RAY DIFFRACTION

▼

3. Official assembly/model SAXS Official SAXS Profiles

This page reads only the latest assembly calculations. Every curve maps to an explicit PDB entry, official biological assembly and coordinate model.

4x2t__assembly_1__model_1

Assembly 1 · Model 1 · CRYSOL 4.1.3-1-20251215 (887e7ef)

Download this curve (.dat)

4x2t__assembly_1__model_1 | I(q)

100 plotted points; both axes use logarithmic scales.

4x2t__assembly_1__model_1 | P(r) · Pending

P(r) will be calculated and displayed separately for the same assembly/model.

Rg（Guinier）	43.40 Å
Rg (electron density)	42.72 Å
Total Rg	42.92 Å
Atom count	23499
Residues	3072
Excluded volume	421530 Å³
Maximum q	0.500 Å⁻¹

Assembly	Model	Structure unit	Oligomeric description	Status	CRYSOL	Actions
1	1	`4x2t__assembly_1__model_1`	hexameric （6）	Success	4.1.3-1-20251215 (887e7ef)	View Download
2	1	`4x2t__assembly_2__model_1`	hexameric （6）	Success	4.1.3-1-20251215 (887e7ef)	View Download

▶

4. Crystallography and Experiment 4. Crystallography & Experiment

▶

5. Entities and Polymers Entities & Polymers (7)

Entity 1 Entity 1 polymer

Description description	M17 leucyl aminopeptidase
Molecular weight formula_weight	57564.6 kDa
Mutation mutation	N152Q, N515Q, N545Q
Source method src_method	man
Copy count entity_count	12

Polymer Polymer

Polymer type type	polypeptide(L)
Chain IDs strand_id	A,B,C,D,E,F,G,H,I,J,K,L
Atom count atom_count	48055

ASEVPQVVSLDPTSIPIEYNTPIHDIKVQVYDIKGGCNVEEGLTIFLVNNPGKENGPVKISSKVNDKQVSEFLKDENMEKFNVKLGTSKHFYMFNDNKNSVAVGYVGCGSVADLSEADMKRVVLSLVTMLHDNKLSKLTVVFEINVDKNLFRFFLETLFYEYMTDERFKSTDKNVNMEYIKHLGVYINNADTYKEEVEKARVYYFGTYYASQLIAAPSNYCNPVSLSNAAVELAQKLNLEYKILGVKELEELKMGAYLSVGKGSMYPNKFIHLTYKSKGDVKKKIALVGKGITFDSGGYNLKAAPGSMIDLMKFDMSGCAAVLGCAYCVGTLKPENVEIHFLSAVCENMVSKNSYRPGDIITASNGKTIEVGNTDAEGRLTLADALVYAEKLGVDYIVDIATLTGAMLYSLGTSYAGVFGNNEELINKILQSSKTSNEPVWWLPIINEYRATLNSKYADINQISSSVKASSIVASLFLKEFVQNTAWAHIDIAGVSWNFKARKPKGFGVRLLTEFVLND

Source Source

Source organism organism	Plasmodium falciparum (isolate 3D7)
NCBI taxonomy ID ncbi_taxonomy_id	36329
Host organism host_organism	Escherichia coli

Entity 2 Entity 2 non-polymer

Description description	ZINC ION
Molecular weight formula_weight	65.4 kDa
Source method src_method	syn
Copy count entity_count	24

Entity 3 Entity 3 non-polymer

Description description	(2S)-({(2R)-2-[(1S)-1-hydroxy-2-(hydroxyamino)-2-oxoethyl]-4-methylpentanoyl}amino)(phenyl)ethanoic acid
Molecular weight formula_weight	338.4 kDa
Source method src_method	syn
Copy count entity_count	11

Entity 4 Entity 4 non-polymer

Description description	CARBONATE ION
Molecular weight formula_weight	60.0 kDa
Source method src_method	syn
Copy count entity_count	12

Entity 5 Entity 5 non-polymer

Description description	SULFATE ION
Molecular weight formula_weight	96.1 kDa
Source method src_method	syn
Copy count entity_count	13

Entity 6 Entity 6 non-polymer

Description description	PENTAETHYLENE GLYCOL
Molecular weight formula_weight	238.3 kDa
Source method src_method	syn
Copy count entity_count	10

Entity 7 Entity 7 water

Description description	water
Molecular weight formula_weight	18.0 kDa
Source method src_method	nat
Copy count entity_count	1031

▼

6. Fold Classification (SCOP + CATH) 24 domains

CATH v4.4 (24 domains)

Domain ID domain_id	4x2tA01
Class class	3 — Alpha Beta
Architecture architecture	40 — 3-Layer(aba) Sandwich
Topology topology	220 — Leucine Aminopeptidase, subunit E; domain 1
Homologous superfamily homologous superfamily	10 — Leucine Aminopeptidase, subunit E, domain 1

Domain ID domain_id	4x2tA02
Class class	3 — Alpha Beta
Architecture architecture	40 — 3-Layer(aba) Sandwich
Topology topology	630 — Aminopeptidase
Homologous superfamily homologous superfamily	10 — Zn peptidases

Domain ID domain_id	4x2tB01
Class class	3 — Alpha Beta
Architecture architecture	40 — 3-Layer(aba) Sandwich
Topology topology	220 — Leucine Aminopeptidase, subunit E; domain 1
Homologous superfamily homologous superfamily	10 — Leucine Aminopeptidase, subunit E, domain 1

Domain ID domain_id	4x2tB02
Class class	3 — Alpha Beta
Architecture architecture	40 — 3-Layer(aba) Sandwich
Topology topology	630 — Aminopeptidase
Homologous superfamily homologous superfamily	10 — Zn peptidases

Domain ID domain_id	4x2tC01
Class class	3 — Alpha Beta
Architecture architecture	40 — 3-Layer(aba) Sandwich
Topology topology	220 — Leucine Aminopeptidase, subunit E; domain 1
Homologous superfamily homologous superfamily	10 — Leucine Aminopeptidase, subunit E, domain 1

Domain ID domain_id	4x2tC02
Class class	3 — Alpha Beta
Architecture architecture	40 — 3-Layer(aba) Sandwich
Topology topology	630 — Aminopeptidase
Homologous superfamily homologous superfamily	10 — Zn peptidases

Domain ID domain_id	4x2tD01
Class class	3 — Alpha Beta
Architecture architecture	40 — 3-Layer(aba) Sandwich
Topology topology	220 — Leucine Aminopeptidase, subunit E; domain 1
Homologous superfamily homologous superfamily	10 — Leucine Aminopeptidase, subunit E, domain 1

Domain ID domain_id	4x2tD02
Class class	3 — Alpha Beta
Architecture architecture	40 — 3-Layer(aba) Sandwich
Topology topology	630 — Aminopeptidase
Homologous superfamily homologous superfamily	10 — Zn peptidases

Domain ID domain_id	4x2tE01
Class class	3 — Alpha Beta
Architecture architecture	40 — 3-Layer(aba) Sandwich
Topology topology	220 — Leucine Aminopeptidase, subunit E; domain 1
Homologous superfamily homologous superfamily	10 — Leucine Aminopeptidase, subunit E, domain 1

Domain ID domain_id	4x2tE02
Class class	3 — Alpha Beta
Architecture architecture	40 — 3-Layer(aba) Sandwich
Topology topology	630 — Aminopeptidase
Homologous superfamily homologous superfamily	10 — Zn peptidases

Domain ID domain_id	4x2tF01
Class class	3 — Alpha Beta
Architecture architecture	40 — 3-Layer(aba) Sandwich
Topology topology	220 — Leucine Aminopeptidase, subunit E; domain 1
Homologous superfamily homologous superfamily	10 — Leucine Aminopeptidase, subunit E, domain 1

Domain ID domain_id	4x2tF02
Class class	3 — Alpha Beta
Architecture architecture	40 — 3-Layer(aba) Sandwich
Topology topology	630 — Aminopeptidase
Homologous superfamily homologous superfamily	10 — Zn peptidases

Domain ID domain_id	4x2tG01
Class class	3 — Alpha Beta
Architecture architecture	40 — 3-Layer(aba) Sandwich
Topology topology	220 — Leucine Aminopeptidase, subunit E; domain 1
Homologous superfamily homologous superfamily	10 — Leucine Aminopeptidase, subunit E, domain 1

Domain ID domain_id	4x2tG02
Class class	3 — Alpha Beta
Architecture architecture	40 — 3-Layer(aba) Sandwich
Topology topology	630 — Aminopeptidase
Homologous superfamily homologous superfamily	10 — Zn peptidases

Domain ID domain_id	4x2tH01
Class class	3 — Alpha Beta
Architecture architecture	40 — 3-Layer(aba) Sandwich
Topology topology	220 — Leucine Aminopeptidase, subunit E; domain 1
Homologous superfamily homologous superfamily	10 — Leucine Aminopeptidase, subunit E, domain 1

Domain ID domain_id	4x2tH02
Class class	3 — Alpha Beta
Architecture architecture	40 — 3-Layer(aba) Sandwich
Topology topology	630 — Aminopeptidase
Homologous superfamily homologous superfamily	10 — Zn peptidases

Domain ID domain_id	4x2tI01
Class class	3 — Alpha Beta
Architecture architecture	40 — 3-Layer(aba) Sandwich
Topology topology	220 — Leucine Aminopeptidase, subunit E; domain 1
Homologous superfamily homologous superfamily	10 — Leucine Aminopeptidase, subunit E, domain 1

Domain ID domain_id	4x2tI02
Class class	3 — Alpha Beta
Architecture architecture	40 — 3-Layer(aba) Sandwich
Topology topology	630 — Aminopeptidase
Homologous superfamily homologous superfamily	10 — Zn peptidases

Domain ID domain_id	4x2tJ01
Class class	3 — Alpha Beta
Architecture architecture	40 — 3-Layer(aba) Sandwich
Topology topology	220 — Leucine Aminopeptidase, subunit E; domain 1
Homologous superfamily homologous superfamily	10 — Leucine Aminopeptidase, subunit E, domain 1

Domain ID domain_id	4x2tJ02
Class class	3 — Alpha Beta
Architecture architecture	40 — 3-Layer(aba) Sandwich
Topology topology	630 — Aminopeptidase
Homologous superfamily homologous superfamily	10 — Zn peptidases

Domain ID domain_id	4x2tK01
Class class	3 — Alpha Beta
Architecture architecture	40 — 3-Layer(aba) Sandwich
Topology topology	220 — Leucine Aminopeptidase, subunit E; domain 1
Homologous superfamily homologous superfamily	10 — Leucine Aminopeptidase, subunit E, domain 1

Domain ID domain_id	4x2tK02
Class class	3 — Alpha Beta
Architecture architecture	40 — 3-Layer(aba) Sandwich
Topology topology	630 — Aminopeptidase
Homologous superfamily homologous superfamily	10 — Zn peptidases

Domain ID domain_id	4x2tL01
Class class	3 — Alpha Beta
Architecture architecture	40 — 3-Layer(aba) Sandwich
Topology topology	220 — Leucine Aminopeptidase, subunit E; domain 1
Homologous superfamily homologous superfamily	10 — Leucine Aminopeptidase, subunit E, domain 1

Domain ID domain_id	4x2tL02
Class class	3 — Alpha Beta
Architecture architecture	40 — 3-Layer(aba) Sandwich
Topology topology	630 — Aminopeptidase
Homologous superfamily homologous superfamily	10 — Zn peptidases

▶

Unit-cell length a length_a	173.715 Å
Unit-cell length b length_b	176.698 Å
Unit-cell length c length_c	223.977 Å
Unit-cell angle α angle_alpha	90.00 °
Unit-cell angle β angle_beta	90.00 °
Unit-cell angle γ angle_gamma	90.00 °
Molecules per unit cell Z z_pdb	48

Space group space_group	P 21 21 21
Space-group number int_tables_number	19
Crystal system crystal_system	—

Resolution resolution	2.729 Å
Low-resolution limit resolution_low	48.748 Å
R factor r_factor	0.2225
R_work r_work	0.2198
R_free r_free	0.2737

X-ray crystal structure of the orally available aminopeptidase inhibitor, Tosedostat, bound to the M17 Leucyl Aminopeptidase from P. falciparum

1. Protein Identity and Related Structures Protein Identity & Related Structures

M17 leucyl aminopeptidase

State in the Current Structure

Other States of the Same Protein in the Database

2. Structure Basics 2. Structure Basics

3. Official assembly/model SAXS Official SAXS Profiles

4x2t__assembly_1__model_1

4x2t__assembly_1__model_1 | I(q)

4x2t__assembly_1__model_1 | P(r) · Pending

4. Crystallography and Experiment 4. Crystallography & Experiment

Unit cell Unit Cell

Symmetry Symmetry

Refinement Refinement

Diffraction experiment Diffraction

5. Entities and Polymers Entities & Polymers (7)

Entity 1 Entity 1 polymer

Polymer Polymer

Source Source

Entity 2 Entity 2 non-polymer

Entity 3 Entity 3 non-polymer

Entity 4 Entity 4 non-polymer

Entity 5 Entity 5 non-polymer

Entity 6 Entity 6 non-polymer

Entity 7 Entity 7 water

6. Fold Classification (SCOP + CATH) 24 domains

CATH v4.4 (24 domains)

7. Citations (1)

X-ray crystal structure of the orally available aminopeptidase inhibitor, Tosedostat, bound to the M17 Leucyl Aminopeptidase from P. falciparum

1. Protein Identity and Related Structures Protein Identity & Related Structures

M17 leucyl aminopeptidase

State in the Current Structure

Other States of the Same Protein in the Database

Monomer

Homodimer

Homotetramer

Other homooligomers

Heteromeric or nucleic-acid complex

2. Structure Basics 2. Structure Basics

3. Official assembly/model SAXS Official SAXS Profiles

4x2t__assembly_1__model_1

4x2t__assembly_1__model_1 | I(q)

4x2t__assembly_1__model_1 | P(r) · Pending

4. Crystallography and Experiment 4. Crystallography & Experiment

Unit cell Unit Cell

Symmetry Symmetry

Refinement Refinement

Diffraction experiment Diffraction

5. Entities and Polymers Entities & Polymers (7)

Entity 1 Entity 1 polymer

Polymer Polymer

Source Source

Entity 2 Entity 2 non-polymer

Entity 3 Entity 3 non-polymer

Entity 4 Entity 4 non-polymer

Entity 5 Entity 5 non-polymer

Entity 6 Entity 6 non-polymer

Entity 7 Entity 7 water

6. Fold Classification (SCOP + CATH) 24 domains

CATH v4.4 (24 domains)

7. Citations (1)