4EU2

Crystal structure of 20s proteasome with novel inhibitor K-7174

Functional Information from GO Data

Chain	GOid	namespace	contents
1	0000502	cellular_component	proteasome complex
1	0003674	molecular_function	molecular_function
1	0005515	molecular_function	protein binding
1	0005634	cellular_component	nucleus
1	0005737	cellular_component	cytoplasm
1	0005829	cellular_component	cytosol
1	0005839	cellular_component	proteasome core complex
1	0010499	biological_process	proteasomal ubiquitin-independent protein catabolic process
1	0019774	cellular_component	proteasome core complex, beta-subunit complex
1	0043161	biological_process	proteasome-mediated ubiquitin-dependent protein catabolic process
1	0051603	biological_process	proteolysis involved in protein catabolic process
2	0005839	cellular_component	proteasome core complex
2	0051603	biological_process	proteolysis involved in protein catabolic process
A	0000502	cellular_component	proteasome complex
A	0003674	molecular_function	molecular_function
A	0005515	molecular_function	protein binding
A	0005634	cellular_component	nucleus
A	0005737	cellular_component	cytoplasm
A	0005739	cellular_component	mitochondrion
A	0005839	cellular_component	proteasome core complex
A	0006511	biological_process	ubiquitin-dependent protein catabolic process
A	0010499	biological_process	proteasomal ubiquitin-independent protein catabolic process
A	0019773	cellular_component	proteasome core complex, alpha-subunit complex
A	0043161	biological_process	proteasome-mediated ubiquitin-dependent protein catabolic process
A	0051603	biological_process	proteolysis involved in protein catabolic process
B	0000502	cellular_component	proteasome complex
B	0003674	molecular_function	molecular_function
B	0005515	molecular_function	protein binding
B	0005634	cellular_component	nucleus
B	0005737	cellular_component	cytoplasm
B	0005839	cellular_component	proteasome core complex
B	0006511	biological_process	ubiquitin-dependent protein catabolic process
B	0010499	biological_process	proteasomal ubiquitin-independent protein catabolic process
B	0019773	cellular_component	proteasome core complex, alpha-subunit complex
B	0034515	cellular_component	proteasome storage granule
B	0043161	biological_process	proteasome-mediated ubiquitin-dependent protein catabolic process
B	0051603	biological_process	proteolysis involved in protein catabolic process
C	0000502	cellular_component	proteasome complex
C	0003674	molecular_function	molecular_function
C	0005515	molecular_function	protein binding
C	0005634	cellular_component	nucleus
C	0005737	cellular_component	cytoplasm
C	0005829	cellular_component	cytosol
C	0005839	cellular_component	proteasome core complex
C	0006511	biological_process	ubiquitin-dependent protein catabolic process
C	0010499	biological_process	proteasomal ubiquitin-independent protein catabolic process
C	0019773	cellular_component	proteasome core complex, alpha-subunit complex
C	0034515	cellular_component	proteasome storage granule
C	0043161	biological_process	proteasome-mediated ubiquitin-dependent protein catabolic process
C	0051603	biological_process	proteolysis involved in protein catabolic process
C	0080129	biological_process	proteasome core complex assembly
D	0000502	cellular_component	proteasome complex
D	0003674	molecular_function	molecular_function
D	0005515	molecular_function	protein binding
D	0005634	cellular_component	nucleus
D	0005737	cellular_component	cytoplasm
D	0005739	cellular_component	mitochondrion
D	0005839	cellular_component	proteasome core complex
D	0006511	biological_process	ubiquitin-dependent protein catabolic process
D	0010499	biological_process	proteasomal ubiquitin-independent protein catabolic process
D	0019773	cellular_component	proteasome core complex, alpha-subunit complex
D	0034515	cellular_component	proteasome storage granule
D	0042175	cellular_component	nuclear outer membrane-endoplasmic reticulum membrane network
D	0043161	biological_process	proteasome-mediated ubiquitin-dependent protein catabolic process
D	0051603	biological_process	proteolysis involved in protein catabolic process
E	0000502	cellular_component	proteasome complex
E	0003674	molecular_function	molecular_function
E	0005515	molecular_function	protein binding
E	0005634	cellular_component	nucleus
E	0005737	cellular_component	cytoplasm
E	0005839	cellular_component	proteasome core complex
E	0006511	biological_process	ubiquitin-dependent protein catabolic process
E	0010499	biological_process	proteasomal ubiquitin-independent protein catabolic process
E	0019773	cellular_component	proteasome core complex, alpha-subunit complex
E	0034515	cellular_component	proteasome storage granule
E	0043161	biological_process	proteasome-mediated ubiquitin-dependent protein catabolic process
E	0051603	biological_process	proteolysis involved in protein catabolic process
F	0000502	cellular_component	proteasome complex
F	0003674	molecular_function	molecular_function
F	0005515	molecular_function	protein binding
F	0005634	cellular_component	nucleus
F	0005737	cellular_component	cytoplasm
F	0005839	cellular_component	proteasome core complex
F	0006511	biological_process	ubiquitin-dependent protein catabolic process
F	0010499	biological_process	proteasomal ubiquitin-independent protein catabolic process
F	0019773	cellular_component	proteasome core complex, alpha-subunit complex
F	0034515	cellular_component	proteasome storage granule
F	0043161	biological_process	proteasome-mediated ubiquitin-dependent protein catabolic process
F	0051603	biological_process	proteolysis involved in protein catabolic process
G	0005839	cellular_component	proteasome core complex
G	0006511	biological_process	ubiquitin-dependent protein catabolic process
G	0019773	cellular_component	proteasome core complex, alpha-subunit complex
G	0051603	biological_process	proteolysis involved in protein catabolic process
H	0000502	cellular_component	proteasome complex
H	0004175	molecular_function	endopeptidase activity
H	0004298	molecular_function	threonine-type endopeptidase activity
H	0005515	molecular_function	protein binding
H	0005634	cellular_component	nucleus
H	0005737	cellular_component	cytoplasm
H	0005829	cellular_component	cytosol
H	0005839	cellular_component	proteasome core complex
H	0006508	biological_process	proteolysis
H	0010499	biological_process	proteasomal ubiquitin-independent protein catabolic process
H	0019774	cellular_component	proteasome core complex, beta-subunit complex
H	0034515	cellular_component	proteasome storage granule
H	0043161	biological_process	proteasome-mediated ubiquitin-dependent protein catabolic process
H	0051603	biological_process	proteolysis involved in protein catabolic process
I	0004298	molecular_function	threonine-type endopeptidase activity
I	0005839	cellular_component	proteasome core complex
I	0051603	biological_process	proteolysis involved in protein catabolic process
J	0000502	cellular_component	proteasome complex
J	0005515	molecular_function	protein binding
J	0005634	cellular_component	nucleus
J	0005737	cellular_component	cytoplasm
J	0005829	cellular_component	cytosol
J	0005839	cellular_component	proteasome core complex
J	0010499	biological_process	proteasomal ubiquitin-independent protein catabolic process
J	0019774	cellular_component	proteasome core complex, beta-subunit complex
J	0043161	biological_process	proteasome-mediated ubiquitin-dependent protein catabolic process
J	0051603	biological_process	proteolysis involved in protein catabolic process
J	0061133	molecular_function	endopeptidase activator activity
K	0000502	cellular_component	proteasome complex
K	0005515	molecular_function	protein binding
K	0005634	cellular_component	nucleus
K	0005737	cellular_component	cytoplasm
K	0005789	cellular_component	endoplasmic reticulum membrane
K	0005829	cellular_component	cytosol
K	0005839	cellular_component	proteasome core complex
K	0010498	biological_process	proteasomal protein catabolic process
K	0010499	biological_process	proteasomal ubiquitin-independent protein catabolic process
K	0019774	cellular_component	proteasome core complex, beta-subunit complex
K	0043161	biological_process	proteasome-mediated ubiquitin-dependent protein catabolic process
K	0051603	biological_process	proteolysis involved in protein catabolic process
K	0061133	molecular_function	endopeptidase activator activity
L	0004298	molecular_function	threonine-type endopeptidase activity
L	0005839	cellular_component	proteasome core complex
L	0051603	biological_process	proteolysis involved in protein catabolic process
M	0000502	cellular_component	proteasome complex
M	0003674	molecular_function	molecular_function
M	0005515	molecular_function	protein binding
M	0005634	cellular_component	nucleus
M	0005737	cellular_component	cytoplasm
M	0005829	cellular_component	cytosol
M	0005839	cellular_component	proteasome core complex
M	0010499	biological_process	proteasomal ubiquitin-independent protein catabolic process
M	0019774	cellular_component	proteasome core complex, beta-subunit complex
M	0043161	biological_process	proteasome-mediated ubiquitin-dependent protein catabolic process
M	0051603	biological_process	proteolysis involved in protein catabolic process
N	0005839	cellular_component	proteasome core complex
N	0051603	biological_process	proteolysis involved in protein catabolic process
O	0000502	cellular_component	proteasome complex
O	0003674	molecular_function	molecular_function
O	0005515	molecular_function	protein binding
O	0005634	cellular_component	nucleus
O	0005737	cellular_component	cytoplasm
O	0005739	cellular_component	mitochondrion
O	0005839	cellular_component	proteasome core complex
O	0006511	biological_process	ubiquitin-dependent protein catabolic process
O	0010499	biological_process	proteasomal ubiquitin-independent protein catabolic process
O	0019773	cellular_component	proteasome core complex, alpha-subunit complex
O	0043161	biological_process	proteasome-mediated ubiquitin-dependent protein catabolic process
O	0051603	biological_process	proteolysis involved in protein catabolic process
P	0000502	cellular_component	proteasome complex
P	0003674	molecular_function	molecular_function
P	0005515	molecular_function	protein binding
P	0005634	cellular_component	nucleus
P	0005737	cellular_component	cytoplasm
P	0005839	cellular_component	proteasome core complex
P	0006511	biological_process	ubiquitin-dependent protein catabolic process
P	0010499	biological_process	proteasomal ubiquitin-independent protein catabolic process
P	0019773	cellular_component	proteasome core complex, alpha-subunit complex
P	0034515	cellular_component	proteasome storage granule
P	0043161	biological_process	proteasome-mediated ubiquitin-dependent protein catabolic process
P	0051603	biological_process	proteolysis involved in protein catabolic process
Q	0000502	cellular_component	proteasome complex
Q	0003674	molecular_function	molecular_function
Q	0005515	molecular_function	protein binding
Q	0005634	cellular_component	nucleus
Q	0005737	cellular_component	cytoplasm
Q	0005829	cellular_component	cytosol
Q	0005839	cellular_component	proteasome core complex
Q	0006511	biological_process	ubiquitin-dependent protein catabolic process
Q	0010499	biological_process	proteasomal ubiquitin-independent protein catabolic process
Q	0019773	cellular_component	proteasome core complex, alpha-subunit complex
Q	0034515	cellular_component	proteasome storage granule
Q	0043161	biological_process	proteasome-mediated ubiquitin-dependent protein catabolic process
Q	0051603	biological_process	proteolysis involved in protein catabolic process
Q	0080129	biological_process	proteasome core complex assembly
R	0000502	cellular_component	proteasome complex
R	0003674	molecular_function	molecular_function
R	0005515	molecular_function	protein binding
R	0005634	cellular_component	nucleus
R	0005737	cellular_component	cytoplasm
R	0005739	cellular_component	mitochondrion
R	0005839	cellular_component	proteasome core complex
R	0006511	biological_process	ubiquitin-dependent protein catabolic process
R	0010499	biological_process	proteasomal ubiquitin-independent protein catabolic process
R	0019773	cellular_component	proteasome core complex, alpha-subunit complex
R	0034515	cellular_component	proteasome storage granule
R	0042175	cellular_component	nuclear outer membrane-endoplasmic reticulum membrane network
R	0043161	biological_process	proteasome-mediated ubiquitin-dependent protein catabolic process
R	0051603	biological_process	proteolysis involved in protein catabolic process
S	0000502	cellular_component	proteasome complex
S	0003674	molecular_function	molecular_function
S	0005515	molecular_function	protein binding
S	0005634	cellular_component	nucleus
S	0005737	cellular_component	cytoplasm
S	0005839	cellular_component	proteasome core complex
S	0006511	biological_process	ubiquitin-dependent protein catabolic process
S	0010499	biological_process	proteasomal ubiquitin-independent protein catabolic process
S	0019773	cellular_component	proteasome core complex, alpha-subunit complex
S	0034515	cellular_component	proteasome storage granule
S	0043161	biological_process	proteasome-mediated ubiquitin-dependent protein catabolic process
S	0051603	biological_process	proteolysis involved in protein catabolic process
T	0000502	cellular_component	proteasome complex
T	0003674	molecular_function	molecular_function
T	0005515	molecular_function	protein binding
T	0005634	cellular_component	nucleus
T	0005737	cellular_component	cytoplasm
T	0005839	cellular_component	proteasome core complex
T	0006511	biological_process	ubiquitin-dependent protein catabolic process
T	0010499	biological_process	proteasomal ubiquitin-independent protein catabolic process
T	0019773	cellular_component	proteasome core complex, alpha-subunit complex
T	0034515	cellular_component	proteasome storage granule
T	0043161	biological_process	proteasome-mediated ubiquitin-dependent protein catabolic process
T	0051603	biological_process	proteolysis involved in protein catabolic process
U	0005839	cellular_component	proteasome core complex
U	0006511	biological_process	ubiquitin-dependent protein catabolic process
U	0019773	cellular_component	proteasome core complex, alpha-subunit complex
U	0051603	biological_process	proteolysis involved in protein catabolic process
V	0000502	cellular_component	proteasome complex
V	0004175	molecular_function	endopeptidase activity
V	0004298	molecular_function	threonine-type endopeptidase activity
V	0005515	molecular_function	protein binding
V	0005634	cellular_component	nucleus
V	0005737	cellular_component	cytoplasm
V	0005829	cellular_component	cytosol
V	0005839	cellular_component	proteasome core complex
V	0006508	biological_process	proteolysis
V	0010499	biological_process	proteasomal ubiquitin-independent protein catabolic process
V	0019774	cellular_component	proteasome core complex, beta-subunit complex
V	0034515	cellular_component	proteasome storage granule
V	0043161	biological_process	proteasome-mediated ubiquitin-dependent protein catabolic process
V	0051603	biological_process	proteolysis involved in protein catabolic process
W	0004298	molecular_function	threonine-type endopeptidase activity
W	0005839	cellular_component	proteasome core complex
W	0051603	biological_process	proteolysis involved in protein catabolic process
X	0000502	cellular_component	proteasome complex
X	0005515	molecular_function	protein binding
X	0005634	cellular_component	nucleus
X	0005737	cellular_component	cytoplasm
X	0005829	cellular_component	cytosol
X	0005839	cellular_component	proteasome core complex
X	0010499	biological_process	proteasomal ubiquitin-independent protein catabolic process
X	0019774	cellular_component	proteasome core complex, beta-subunit complex
X	0043161	biological_process	proteasome-mediated ubiquitin-dependent protein catabolic process
X	0051603	biological_process	proteolysis involved in protein catabolic process
X	0061133	molecular_function	endopeptidase activator activity
Y	0000502	cellular_component	proteasome complex
Y	0005515	molecular_function	protein binding
Y	0005634	cellular_component	nucleus
Y	0005737	cellular_component	cytoplasm
Y	0005789	cellular_component	endoplasmic reticulum membrane
Y	0005829	cellular_component	cytosol
Y	0005839	cellular_component	proteasome core complex
Y	0010498	biological_process	proteasomal protein catabolic process
Y	0010499	biological_process	proteasomal ubiquitin-independent protein catabolic process
Y	0019774	cellular_component	proteasome core complex, beta-subunit complex
Y	0043161	biological_process	proteasome-mediated ubiquitin-dependent protein catabolic process
Y	0051603	biological_process	proteolysis involved in protein catabolic process
Y	0061133	molecular_function	endopeptidase activator activity
Z	0004298	molecular_function	threonine-type endopeptidase activity
Z	0005839	cellular_component	proteasome core complex
Z	0051603	biological_process	proteolysis involved in protein catabolic process

Functional Information from PDB Data

site_id	AC1
Number of Residues	7
Details	BINDING SITE FOR RESIDUE WPI H 300

Chain	Residue
H	THR1
H	GLY128
H	SER129
H	HOH420
N	PRO-5
N	THR-2
N	TYR22

---

site_id	AC2
Number of Residues	7
Details	BINDING SITE FOR RESIDUE WPI I 301

Chain	Residue
I	THR1
I	ALA46
I	GLY47
I	GLY128
I	SER129
1	TYR24
H	THR22

---

site_id	AC3
Number of Residues	10
Details	BINDING SITE FOR RESIDUE WPI L 301

Chain	Residue
K	MET-1
K	ARG22
K	GLY23
L	THR1
L	GLY47
L	MET97
L	ASP118
L	GLY130
L	SER131
L	HOH426

---

site_id	AC4
Number of Residues	8
Details	BINDING SITE FOR RESIDUE WPI V 201

Chain	Residue
2	PRO-5
2	GLN-6
2	ARG182
V	SER46
V	THR94
V	LEU115
V	GLY128
V	SER129

---

site_id	AC5
Number of Residues	5
Details	BINDING SITE FOR RESIDUE WPI W 301

Chain	Residue
V	THR94
W	THR1
W	GLY47
W	TYR97
W	SER129

---

site_id	AC6
Number of Residues	7
Details	BINDING SITE FOR RESIDUE WPI Z 301

Chain	Residue
Y	GLU48
Y	GLN98
Z	THR1
Z	LYS91
Z	ASP118
Z	GLY130
Z	SER131

---

Functional Information from PROSITE/UniProt

site_id	PS00388
Number of Residues	23
Details	PROTEASOME_ALPHA_1 Proteasome alpha-type subunits signature. YdsrtTiFSPeGRlyQVEYAleS

Chain	Residue	Details
C	TYR6-SER28
D	TYR4-ALA26
B	TYR5-ALA27
A	TYR12-ALA34
F	TYR6-ALA28
G	TYR7-ALA29

---

site_id	PS00854
Number of Residues	47
Details	PROTEASOME_BETA_1 Proteasome beta-type subunits signature. VAMtGkdCVAIACDlrlgsqslgvsnkfe.Kifhyghvflgit.GlaTD

Chain	Residue	Details
J	VAL4-ASP50
C	ILE36-ASP83
1	LEU4-ASP51
D	VAL34-ASP81
2	ILE4-ASP51
L	LEU4-ASP51
K	LEU4-ASP51
I	VAL4-ASP51
H	MET4-ASP51

---

Functional Information from SwissProt/UniProt

site_id	SWS_FT_FI1
Number of Residues	2
Details	ACT_SITE: Nucleophile => ECO:0000269|PubMed:9087403

Chain	Residue	Details
L	THR1
Z	THR1
C	LYS199
C	LYS231
Q	LYS100
Q	LYS199
Q	LYS231

---

site_id	SWS_FT_FI2
Number of Residues	2
Details	BINDING:

Chain	Residue	Details
L	ALA49
Z	ALA49
X	LYS61

---

Catalytic Information from CSA

site_id	MCSA1
Number of Residues	8
Details	M-CSA 177

Chain	Residue	Details
I	THR1	covalently attached, hydrogen bond acceptor, hydrogen bond donor, nucleofuge, nucleophile, proton acceptor, proton donor
I	ASP17	activator, steric locator
I	ARG19	activator
I	LYS33	activator, electrostatic stabiliser
I	GLY47	electrostatic stabiliser
I	SER129	activator, electrostatic stabiliser
I	ASP166	activator, steric locator
I	SER169	activator, electrostatic stabiliser

---

site_id	MCSA2
Number of Residues	8
Details	M-CSA 177

Chain	Residue	Details
W	THR1	covalently attached, hydrogen bond acceptor, hydrogen bond donor, nucleofuge, nucleophile, proton acceptor, proton donor
W	ASP17	activator, steric locator
W	ARG19	activator
W	LYS33	activator, electrostatic stabiliser
W	GLY47	electrostatic stabiliser
W	SER129	activator, electrostatic stabiliser
W	ASP166	activator, steric locator
W	SER169	activator, electrostatic stabiliser

---