4hw2

Discovery of potent Mcl-1 inhibitors using fragment-based methods and structure-based design

Method: X-RAY DIFFRACTION

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

Induced myeloid leukemia cell differentiation protein Mcl-1

Homo sapiens

State in the Current Structure

Assembly	Physical composition	Protein state	Molecular copy count	Associated components	Data consistency
1	Protein monomer	Monomer	Protein 1	6-chloro-3-[3-(4-chloro-3,5-dimethylphenoxy)propyl]-1H-indole-2-carboxylic acid × 1 TRIETHYLENE GLYCOL × 1	Consistent with protein count
2	Protein monomer	Monomer	Protein 1	6-chloro-3-[3-(4-chloro-3,5-dimethylphenoxy)propyl]-1H-indole-2-carboxylic acid × 1 TRIETHYLENE GLYCOL × 2 1,2-ETHANEDIOL × 1	Consistent with protein count
3	Protein monomer	Monomer	Protein 1	6-chloro-3-[3-(4-chloro-3,5-dimethylphenoxy)propyl]-1H-indole-2-carboxylic acid × 1	Consistent with protein count
4	Protein monomer	Monomer	Protein 1	6-chloro-3-[3-(4-chloro-3,5-dimethylphenoxy)propyl]-1H-indole-2-carboxylic acid × 1	Consistent with protein count
5	Protein monomer	Monomer	Protein 1	6-chloro-3-[3-(4-chloro-3,5-dimethylphenoxy)propyl]-1H-indole-2-carboxylic acid × 1	Consistent with protein count
6	Protein monomer	Monomer	Protein 1	6-chloro-3-[3-(4-chloro-3,5-dimethylphenoxy)propyl]-1H-indole-2-carboxylic acid × 1	Consistent with protein count

Other States of the Same Protein in the Database

View Construct and Data Evidence

UniProt name	MCL1_HUMAN
Isoform	—
PDB entities	1
Chains and sequence ranges	Author chain A； PDBConstruct 2–153； UniProt 172–323 Author chain B； PDBConstruct 2–153； UniProt 172–323 Author chain C； PDBConstruct 2–153； UniProt 172–323 Author chain D； PDBConstruct 2–153； UniProt 172–323 Author chain E； PDBConstruct 2–153； UniProt 172–323 Author chain F； PDBConstruct 2–153； UniProt 172–323

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.

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2. Structure Basics 2. Structure Basics

Entry ID entry_id	4hw2
Deposition date deposition_date	2012-11-07
Structure title title	Discovery of potent Mcl-1 inhibitors using fragment-based methods and structure-based design
Keywords keywords	regulation of apoptosis, maintenance of viability, APOPTOSIS, APOPTOSIS-INHIBITOR complex; APOPTOSIS/INHIBITOR
Experimental Method method	X-RAY DIFFRACTION

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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.

4hw2__assembly_5__model_1

Assembly 5 · Model 1 · CRYSOL 4.1.3-1-20251215 (887e7ef)

Download this curve (.dat)

4hw2__assembly_5__model_1 | I(q)

100 plotted points; both axes use logarithmic scales.

4hw2__assembly_5__model_1 | P(r) · Pending

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

Rg（Guinier）	16.25 Å
Rg (electron density)	14.73 Å
Total Rg	15.94 Å
Atom count	1235
Residues	151
Excluded volume	21975 Å³
Maximum q	0.500 Å⁻¹

Assembly	Model	Structure unit	Oligomeric description	Status	CRYSOL	Actions
1	1	`4hw2__assembly_1__model_1`	monomeric （1）	Success	4.1.3-1-20251215 (887e7ef)	View Download
2	1	`4hw2__assembly_2__model_1`	monomeric （1）	Success	4.1.3-1-20251215 (887e7ef)	View Download
3	1	`4hw2__assembly_3__model_1`	monomeric （1）	Success	4.1.3-1-20251215 (887e7ef)	View Download
4	1	`4hw2__assembly_4__model_1`	monomeric （1）	Success	4.1.3-1-20251215 (887e7ef)	View Download
5	1	`4hw2__assembly_5__model_1`	monomeric （1）	Success	4.1.3-1-20251215 (887e7ef)	View Download
6	1	`4hw2__assembly_6__model_1`	monomeric （1）	Success	4.1.3-1-20251215 (887e7ef)	View Download

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4. Crystallography and Experiment 4. Crystallography & Experiment

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5. Entities and Polymers Entities & Polymers (4)

Entity 1 Entity 1 polymer

Description description	Induced myeloid leukemia cell differentiation protein Mcl-1
Molecular weight formula_weight	17493.9 kDa
Source method src_method	man
Copy count entity_count	6

Polymer Polymer

Polymer type type	polypeptide(L)
Chain IDs strand_id	A,B,C,D,E,F
Atom count atom_count	7376

GDELYRQSLEIISRYLREQATGAKDTKPMGRSGATSRKALETLRRVGDGVQRNHETAFQGMLRKLDIKNEDDVKSLSRVMIHVFSDGVTNWGRIVTLISFGAFVAKHLKTINQESCIEPLAESITDVLVRTKRDWLVKQRGWDGFVEFFHVED

Source Source

Source organism organism	Homo sapiens
Common name common_name	human
NCBI taxonomy ID ncbi_taxonomy_id	9606
Host organism host_organism	Escherichia coli

Entity 2 Entity 2 non-polymer

Description description	6-chloro-3-[3-(4-chloro-3,5-dimethylphenoxy)propyl]-1H-indole-2-carboxylic acid
Molecular weight formula_weight	392.3 kDa
Source method src_method	syn
Copy count entity_count	6

Entity 3 Entity 3 non-polymer

Description description	TRIETHYLENE GLYCOL
Molecular weight formula_weight	150.2 kDa
Source method src_method	syn
Copy count entity_count	3

Entity 4 Entity 4 non-polymer

Description description	1,2-ETHANEDIOL
Molecular weight formula_weight	62.1 kDa
Source method src_method	syn
Copy count entity_count	1

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6. Fold Classification (SCOP + CATH) 18 domains

SCOP 2.08 (12 domains)

Domain ID domain_id	d4hw2a1
Class class	f — Membrane and cell surface proteins and peptides
Fold Fold fold	f.1 — Toxins' membrane translocation domains
Superfamily Superfamily superfamily	f.1.4 — Bcl-2 inhibitors of programmed cell death
Family Family family	f.1.4.1 — Bcl-2 inhibitors of programmed cell death

Domain ID domain_id	d4hw2a2
Class class	l — Artifacts
Fold Fold fold	l.1 — Tags
Superfamily Superfamily superfamily	l.1.1 — Tags
Family Family family	l.1.1.1 — Tags

Domain ID domain_id	d4hw2b1
Class class	f — Membrane and cell surface proteins and peptides
Fold Fold fold	f.1 — Toxins' membrane translocation domains
Superfamily Superfamily superfamily	f.1.4 — Bcl-2 inhibitors of programmed cell death
Family Family family	f.1.4.1 — Bcl-2 inhibitors of programmed cell death

Domain ID domain_id	d4hw2b2
Class class	l — Artifacts
Fold Fold fold	l.1 — Tags
Superfamily Superfamily superfamily	l.1.1 — Tags
Family Family family	l.1.1.1 — Tags

Domain ID domain_id	d4hw2c1
Class class	f — Membrane and cell surface proteins and peptides
Fold Fold fold	f.1 — Toxins' membrane translocation domains
Superfamily Superfamily superfamily	f.1.4 — Bcl-2 inhibitors of programmed cell death
Family Family family	f.1.4.1 — Bcl-2 inhibitors of programmed cell death

Domain ID domain_id	d4hw2c2
Class class	l — Artifacts
Fold Fold fold	l.1 — Tags
Superfamily Superfamily superfamily	l.1.1 — Tags
Family Family family	l.1.1.1 — Tags

Domain ID domain_id	d4hw2d1
Class class	f — Membrane and cell surface proteins and peptides
Fold Fold fold	f.1 — Toxins' membrane translocation domains
Superfamily Superfamily superfamily	f.1.4 — Bcl-2 inhibitors of programmed cell death
Family Family family	f.1.4.1 — Bcl-2 inhibitors of programmed cell death

Domain ID domain_id	d4hw2d2
Class class	l — Artifacts
Fold Fold fold	l.1 — Tags
Superfamily Superfamily superfamily	l.1.1 — Tags
Family Family family	l.1.1.1 — Tags

Domain ID domain_id	d4hw2e1
Class class	f — Membrane and cell surface proteins and peptides
Fold Fold fold	f.1 — Toxins' membrane translocation domains
Superfamily Superfamily superfamily	f.1.4 — Bcl-2 inhibitors of programmed cell death
Family Family family	f.1.4.1 — Bcl-2 inhibitors of programmed cell death

Domain ID domain_id	d4hw2e2
Class class	l — Artifacts
Fold Fold fold	l.1 — Tags
Superfamily Superfamily superfamily	l.1.1 — Tags
Family Family family	l.1.1.1 — Tags

Domain ID domain_id	d4hw2f1
Class class	f — Membrane and cell surface proteins and peptides
Fold Fold fold	f.1 — Toxins' membrane translocation domains
Superfamily Superfamily superfamily	f.1.4 — Bcl-2 inhibitors of programmed cell death
Family Family family	f.1.4.1 — Bcl-2 inhibitors of programmed cell death

Domain ID domain_id	d4hw2f2
Class class	l — Artifacts
Fold Fold fold	l.1 — Tags
Superfamily Superfamily superfamily	l.1.1 — Tags
Family Family family	l.1.1.1 — Tags

CATH v4.4 (6 domains)

Domain ID domain_id	4hw2A01
Class class	1 — Mainly Alpha
Architecture architecture	10 — Orthogonal Bundle
Topology topology	437 — Apoptosis Regulator Bcl-x
Homologous superfamily homologous superfamily	10 — Blc2-like

Domain ID domain_id	4hw2B01
Class class	1 — Mainly Alpha
Architecture architecture	10 — Orthogonal Bundle
Topology topology	437 — Apoptosis Regulator Bcl-x
Homologous superfamily homologous superfamily	10 — Blc2-like

Domain ID domain_id	4hw2C01
Class class	1 — Mainly Alpha
Architecture architecture	10 — Orthogonal Bundle
Topology topology	437 — Apoptosis Regulator Bcl-x
Homologous superfamily homologous superfamily	10 — Blc2-like

Domain ID domain_id	4hw2D01
Class class	1 — Mainly Alpha
Architecture architecture	10 — Orthogonal Bundle
Topology topology	437 — Apoptosis Regulator Bcl-x
Homologous superfamily homologous superfamily	10 — Blc2-like

Domain ID domain_id	4hw2E01
Class class	1 — Mainly Alpha
Architecture architecture	10 — Orthogonal Bundle
Topology topology	437 — Apoptosis Regulator Bcl-x
Homologous superfamily homologous superfamily	10 — Blc2-like

Domain ID domain_id	4hw2F01
Class class	1 — Mainly Alpha
Architecture architecture	10 — Orthogonal Bundle
Topology topology	437 — Apoptosis Regulator Bcl-x
Homologous superfamily homologous superfamily	10 — Blc2-like

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Unit-cell length a length_a	121.997 Å
Unit-cell length b length_b	134.327 Å
Unit-cell length c length_c	62.043 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	24

Space group space_group	P 21 21 2
Space-group number int_tables_number	18
Crystal system crystal_system	—

Resolution resolution	2.800 Å
Low-resolution limit resolution_low	30.000 Å
R factor r_factor	0.2169
R_work r_work	0.2169
R_free r_free	0.2452

Discovery of potent Mcl-1 inhibitors using fragment-based methods and structure-based design

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

Induced myeloid leukemia cell differentiation protein Mcl-1

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

4hw2__assembly_5__model_1

4hw2__assembly_5__model_1 | I(q)

4hw2__assembly_5__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 (4)

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

6. Fold Classification (SCOP + CATH) 18 domains

SCOP 2.08 (12 domains)

CATH v4.4 (6 domains)

7. Citations (1)

Discovery of potent Mcl-1 inhibitors using fragment-based methods and structure-based design

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

Induced myeloid leukemia cell differentiation protein Mcl-1

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

4hw2__assembly_5__model_1

4hw2__assembly_5__model_1 | I(q)

4hw2__assembly_5__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 (4)

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

6. Fold Classification (SCOP + CATH) 18 domains

SCOP 2.08 (12 domains)

CATH v4.4 (6 domains)

7. Citations (1)