6AVO

Cryo-EM structure of human immunoproteasome with a novel noncompetitive inhibitor that selectively inhibits activated lymphocytes

Functional Information from GO Data

Chain	GOid	namespace	contents
A	0000502	cellular_component	proteasome complex
A	0002376	biological_process	immune system process
A	0004175	molecular_function	endopeptidase activity
A	0004298	molecular_function	threonine-type endopeptidase activity
A	0005515	molecular_function	protein binding
A	0005634	cellular_component	nucleus
A	0005654	cellular_component	nucleoplasm
A	0005737	cellular_component	cytoplasm
A	0005829	cellular_component	cytosol
A	0005839	cellular_component	proteasome core complex
A	0006508	biological_process	proteolysis
A	0019774	cellular_component	proteasome core complex, beta-subunit complex
A	0043161	biological_process	proteasome-mediated ubiquitin-dependent protein catabolic process
A	0051603	biological_process	proteolysis involved in protein catabolic process
A	0070062	cellular_component	extracellular exosome
A	1990111	cellular_component	spermatoproteasome complex
A	2000116	biological_process	regulation of cysteine-type endopeptidase activity
B	0004298	molecular_function	threonine-type endopeptidase activity
B	0005839	cellular_component	proteasome core complex
B	0051603	biological_process	proteolysis involved in protein catabolic process
C	0004298	molecular_function	threonine-type endopeptidase activity
C	0005839	cellular_component	proteasome core complex
C	0051603	biological_process	proteolysis involved in protein catabolic process
D	0004298	molecular_function	threonine-type endopeptidase activity
D	0005839	cellular_component	proteasome core complex
D	0051603	biological_process	proteolysis involved in protein catabolic process
E	0004298	molecular_function	threonine-type endopeptidase activity
E	0005839	cellular_component	proteasome core complex
E	0051603	biological_process	proteolysis involved in protein catabolic process
F	0000502	cellular_component	proteasome complex
F	0002376	biological_process	immune system process
F	0004175	molecular_function	endopeptidase activity
F	0004298	molecular_function	threonine-type endopeptidase activity
F	0005515	molecular_function	protein binding
F	0005634	cellular_component	nucleus
F	0005654	cellular_component	nucleoplasm
F	0005737	cellular_component	cytoplasm
F	0005829	cellular_component	cytosol
F	0005839	cellular_component	proteasome core complex
F	0006508	biological_process	proteolysis
F	0019774	cellular_component	proteasome core complex, beta-subunit complex
F	0043161	biological_process	proteasome-mediated ubiquitin-dependent protein catabolic process
F	0051603	biological_process	proteolysis involved in protein catabolic process
F	0070062	cellular_component	extracellular exosome
F	1990111	cellular_component	spermatoproteasome complex
F	2000116	biological_process	regulation of cysteine-type endopeptidase activity
G	0000502	cellular_component	proteasome complex
G	0001530	molecular_function	lipopolysaccharide binding
G	0002376	biological_process	immune system process
G	0002862	biological_process	negative regulation of inflammatory response to antigenic stimulus
G	0005515	molecular_function	protein binding
G	0005634	cellular_component	nucleus
G	0005654	cellular_component	nucleoplasm
G	0005737	cellular_component	cytoplasm
G	0005813	cellular_component	centrosome
G	0005829	cellular_component	cytosol
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	0043161	biological_process	proteasome-mediated ubiquitin-dependent protein catabolic process
G	0051603	biological_process	proteolysis involved in protein catabolic process
G	0070062	cellular_component	extracellular exosome
H	0000502	cellular_component	proteasome complex
H	0005515	molecular_function	protein binding
H	0005576	cellular_component	extracellular region
H	0005634	cellular_component	nucleus
H	0005654	cellular_component	nucleoplasm
H	0005737	cellular_component	cytoplasm
H	0005829	cellular_component	cytosol
H	0005839	cellular_component	proteasome core complex
H	0006511	biological_process	ubiquitin-dependent protein catabolic process
H	0019773	cellular_component	proteasome core complex, alpha-subunit complex
H	0034774	cellular_component	secretory granule lumen
H	0043161	biological_process	proteasome-mediated ubiquitin-dependent protein catabolic process
H	0051603	biological_process	proteolysis involved in protein catabolic process
H	0070062	cellular_component	extracellular exosome
H	1904813	cellular_component	ficolin-1-rich granule lumen
I	0000502	cellular_component	proteasome complex
I	0005515	molecular_function	protein binding
I	0005634	cellular_component	nucleus
I	0005654	cellular_component	nucleoplasm
I	0005737	cellular_component	cytoplasm
I	0005829	cellular_component	cytosol
I	0005839	cellular_component	proteasome core complex
I	0006511	biological_process	ubiquitin-dependent protein catabolic process
I	0019773	cellular_component	proteasome core complex, alpha-subunit complex
I	0042802	molecular_function	identical protein binding
I	0043161	biological_process	proteasome-mediated ubiquitin-dependent protein catabolic process
I	0051603	biological_process	proteolysis involved in protein catabolic process
I	0070062	cellular_component	extracellular exosome
J	0000502	cellular_component	proteasome complex
J	0005515	molecular_function	protein binding
J	0005634	cellular_component	nucleus
J	0005654	cellular_component	nucleoplasm
J	0005737	cellular_component	cytoplasm
J	0005829	cellular_component	cytosol
J	0005839	cellular_component	proteasome core complex
J	0006511	biological_process	ubiquitin-dependent protein catabolic process
J	0019773	cellular_component	proteasome core complex, alpha-subunit complex
J	0031625	molecular_function	ubiquitin protein ligase binding
J	0043161	biological_process	proteasome-mediated ubiquitin-dependent protein catabolic process
J	0045202	cellular_component	synapse
J	0051603	biological_process	proteolysis involved in protein catabolic process
J	0052548	biological_process	regulation of endopeptidase activity
J	0070062	cellular_component	extracellular exosome
K	0000502	cellular_component	proteasome complex
K	0000932	cellular_component	P-body
K	0003723	molecular_function	RNA binding
K	0004175	molecular_function	endopeptidase activity
K	0005515	molecular_function	protein binding
K	0005634	cellular_component	nucleus
K	0005654	cellular_component	nucleoplasm
K	0005737	cellular_component	cytoplasm
K	0005829	cellular_component	cytosol
K	0005839	cellular_component	proteasome core complex
K	0005840	cellular_component	ribosome
K	0006511	biological_process	ubiquitin-dependent protein catabolic process
K	0016363	cellular_component	nuclear matrix
K	0019773	cellular_component	proteasome core complex, alpha-subunit complex
K	0030016	cellular_component	myofibril
K	0030017	cellular_component	sarcomere
K	0035639	molecular_function	purine ribonucleoside triphosphate binding
K	0043161	biological_process	proteasome-mediated ubiquitin-dependent protein catabolic process
K	0050727	biological_process	regulation of inflammatory response
K	0051059	molecular_function	NF-kappaB binding
K	0051092	biological_process	positive regulation of NF-kappaB transcription factor activity
K	0051603	biological_process	proteolysis involved in protein catabolic process
K	0070062	cellular_component	extracellular exosome
L	0000502	cellular_component	proteasome complex
L	0001530	molecular_function	lipopolysaccharide binding
L	0002376	biological_process	immune system process
L	0002862	biological_process	negative regulation of inflammatory response to antigenic stimulus
L	0005515	molecular_function	protein binding
L	0005634	cellular_component	nucleus
L	0005654	cellular_component	nucleoplasm
L	0005737	cellular_component	cytoplasm
L	0005813	cellular_component	centrosome
L	0005829	cellular_component	cytosol
L	0005839	cellular_component	proteasome core complex
L	0006511	biological_process	ubiquitin-dependent protein catabolic process
L	0019773	cellular_component	proteasome core complex, alpha-subunit complex
L	0043161	biological_process	proteasome-mediated ubiquitin-dependent protein catabolic process
L	0051603	biological_process	proteolysis involved in protein catabolic process
L	0070062	cellular_component	extracellular exosome
M	0000502	cellular_component	proteasome complex
M	0005515	molecular_function	protein binding
M	0005576	cellular_component	extracellular region
M	0005634	cellular_component	nucleus
M	0005654	cellular_component	nucleoplasm
M	0005737	cellular_component	cytoplasm
M	0005829	cellular_component	cytosol
M	0005839	cellular_component	proteasome core complex
M	0006511	biological_process	ubiquitin-dependent protein catabolic process
M	0019773	cellular_component	proteasome core complex, alpha-subunit complex
M	0034774	cellular_component	secretory granule lumen
M	0043161	biological_process	proteasome-mediated ubiquitin-dependent protein catabolic process
M	0051603	biological_process	proteolysis involved in protein catabolic process
M	0070062	cellular_component	extracellular exosome
M	1904813	cellular_component	ficolin-1-rich granule lumen
N	0000502	cellular_component	proteasome complex
N	0005515	molecular_function	protein binding
N	0005634	cellular_component	nucleus
N	0005654	cellular_component	nucleoplasm
N	0005737	cellular_component	cytoplasm
N	0005829	cellular_component	cytosol
N	0005839	cellular_component	proteasome core complex
N	0006511	biological_process	ubiquitin-dependent protein catabolic process
N	0019773	cellular_component	proteasome core complex, alpha-subunit complex
N	0042802	molecular_function	identical protein binding
N	0043161	biological_process	proteasome-mediated ubiquitin-dependent protein catabolic process
N	0051603	biological_process	proteolysis involved in protein catabolic process
N	0070062	cellular_component	extracellular exosome
O	0000502	cellular_component	proteasome complex
O	0000932	cellular_component	P-body
O	0005515	molecular_function	protein binding
O	0005634	cellular_component	nucleus
O	0005654	cellular_component	nucleoplasm
O	0005737	cellular_component	cytoplasm
O	0005829	cellular_component	cytosol
O	0005839	cellular_component	proteasome core complex
O	0006511	biological_process	ubiquitin-dependent 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	0043231	cellular_component	intracellular membrane-bounded organelle
O	0051603	biological_process	proteolysis involved in protein catabolic process
O	0070062	cellular_component	extracellular exosome
P	0000502	cellular_component	proteasome complex
P	0000932	cellular_component	P-body
P	0005515	molecular_function	protein binding
P	0005576	cellular_component	extracellular region
P	0005634	cellular_component	nucleus
P	0005654	cellular_component	nucleoplasm
P	0005737	cellular_component	cytoplasm
P	0005829	cellular_component	cytosol
P	0005839	cellular_component	proteasome core complex
P	0006511	biological_process	ubiquitin-dependent protein catabolic process
P	0009615	biological_process	response to virus
P	0019773	cellular_component	proteasome core complex, alpha-subunit complex
P	0034774	cellular_component	secretory granule lumen
P	0043161	biological_process	proteasome-mediated ubiquitin-dependent protein catabolic process
P	0051603	biological_process	proteolysis involved in protein catabolic process
P	0070062	cellular_component	extracellular exosome
P	1904813	cellular_component	ficolin-1-rich granule lumen
Q	0000502	cellular_component	proteasome complex
Q	0005515	molecular_function	protein binding
Q	0005634	cellular_component	nucleus
Q	0005654	cellular_component	nucleoplasm
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	0019773	cellular_component	proteasome core complex, alpha-subunit complex
Q	0031625	molecular_function	ubiquitin protein ligase binding
Q	0043161	biological_process	proteasome-mediated ubiquitin-dependent protein catabolic process
Q	0045202	cellular_component	synapse
Q	0051603	biological_process	proteolysis involved in protein catabolic process
Q	0052548	biological_process	regulation of endopeptidase activity
Q	0070062	cellular_component	extracellular exosome
R	0000502	cellular_component	proteasome complex
R	0000932	cellular_component	P-body
R	0003723	molecular_function	RNA binding
R	0004175	molecular_function	endopeptidase activity
R	0005515	molecular_function	protein binding
R	0005634	cellular_component	nucleus
R	0005654	cellular_component	nucleoplasm
R	0005737	cellular_component	cytoplasm
R	0005829	cellular_component	cytosol
R	0005839	cellular_component	proteasome core complex
R	0005840	cellular_component	ribosome
R	0006511	biological_process	ubiquitin-dependent protein catabolic process
R	0016363	cellular_component	nuclear matrix
R	0019773	cellular_component	proteasome core complex, alpha-subunit complex
R	0030016	cellular_component	myofibril
R	0030017	cellular_component	sarcomere
R	0035639	molecular_function	purine ribonucleoside triphosphate binding
R	0043161	biological_process	proteasome-mediated ubiquitin-dependent protein catabolic process
R	0050727	biological_process	regulation of inflammatory response
R	0051059	molecular_function	NF-kappaB binding
R	0051092	biological_process	positive regulation of NF-kappaB transcription factor activity
R	0051603	biological_process	proteolysis involved in protein catabolic process
R	0070062	cellular_component	extracellular exosome
S	0005839	cellular_component	proteasome core complex
S	0051603	biological_process	proteolysis involved in protein catabolic process
T	0000502	cellular_component	proteasome complex
T	0005515	molecular_function	protein binding
T	0005634	cellular_component	nucleus
T	0005654	cellular_component	nucleoplasm
T	0005737	cellular_component	cytoplasm
T	0005829	cellular_component	cytosol
T	0005839	cellular_component	proteasome core complex
T	0010498	biological_process	proteasomal protein catabolic process
T	0014070	biological_process	response to organic cyclic compound
T	0016020	cellular_component	membrane
T	0019774	cellular_component	proteasome core complex, beta-subunit complex
T	0043161	biological_process	proteasome-mediated ubiquitin-dependent protein catabolic process
T	0051603	biological_process	proteolysis involved in protein catabolic process
T	0070062	cellular_component	extracellular exosome
U	0000502	cellular_component	proteasome complex
U	0005515	molecular_function	protein binding
U	0005634	cellular_component	nucleus
U	0005654	cellular_component	nucleoplasm
U	0005737	cellular_component	cytoplasm
U	0005829	cellular_component	cytosol
U	0005839	cellular_component	proteasome core complex
U	0019774	cellular_component	proteasome core complex, beta-subunit complex
U	0043161	biological_process	proteasome-mediated ubiquitin-dependent protein catabolic process
U	0051603	biological_process	proteolysis involved in protein catabolic process
U	0070062	cellular_component	extracellular exosome
V	0000502	cellular_component	proteasome complex
V	0005515	molecular_function	protein binding
V	0005634	cellular_component	nucleus
V	0005654	cellular_component	nucleoplasm
V	0005737	cellular_component	cytoplasm
V	0005829	cellular_component	cytosol
V	0005839	cellular_component	proteasome core complex
V	0010498	biological_process	proteasomal protein catabolic process
V	0014070	biological_process	response to organic cyclic compound
V	0016020	cellular_component	membrane
V	0019774	cellular_component	proteasome core complex, beta-subunit complex
V	0043161	biological_process	proteasome-mediated ubiquitin-dependent protein catabolic process
V	0051603	biological_process	proteolysis involved in protein catabolic process
V	0070062	cellular_component	extracellular exosome
W	0005839	cellular_component	proteasome core complex
W	0051603	biological_process	proteolysis involved in protein catabolic process
X	0005839	cellular_component	proteasome core complex
X	0051603	biological_process	proteolysis involved in protein catabolic process
Y	0000502	cellular_component	proteasome complex
Y	0005515	molecular_function	protein binding
Y	0005634	cellular_component	nucleus
Y	0005654	cellular_component	nucleoplasm
Y	0005737	cellular_component	cytoplasm
Y	0005829	cellular_component	cytosol
Y	0005839	cellular_component	proteasome core complex
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	0070062	cellular_component	extracellular exosome
Z	0000502	cellular_component	proteasome complex
Z	0000932	cellular_component	P-body
Z	0005515	molecular_function	protein binding
Z	0005634	cellular_component	nucleus
Z	0005654	cellular_component	nucleoplasm
Z	0005737	cellular_component	cytoplasm
Z	0005829	cellular_component	cytosol
Z	0005839	cellular_component	proteasome core complex
Z	0006511	biological_process	ubiquitin-dependent protein catabolic process
Z	0019773	cellular_component	proteasome core complex, alpha-subunit complex
Z	0043161	biological_process	proteasome-mediated ubiquitin-dependent protein catabolic process
Z	0043231	cellular_component	intracellular membrane-bounded organelle
Z	0051603	biological_process	proteolysis involved in protein catabolic process
Z	0070062	cellular_component	extracellular exosome
a	0005839	cellular_component	proteasome core complex
a	0051603	biological_process	proteolysis involved in protein catabolic process
b	0000502	cellular_component	proteasome complex
b	0000932	cellular_component	P-body
b	0005515	molecular_function	protein binding
b	0005576	cellular_component	extracellular region
b	0005634	cellular_component	nucleus
b	0005654	cellular_component	nucleoplasm
b	0005737	cellular_component	cytoplasm
b	0005829	cellular_component	cytosol
b	0005839	cellular_component	proteasome core complex
b	0006511	biological_process	ubiquitin-dependent protein catabolic process
b	0009615	biological_process	response to virus
b	0019773	cellular_component	proteasome core complex, alpha-subunit complex
b	0034774	cellular_component	secretory granule lumen
b	0043161	biological_process	proteasome-mediated ubiquitin-dependent protein catabolic process
b	0051603	biological_process	proteolysis involved in protein catabolic process
b	0070062	cellular_component	extracellular exosome
b	1904813	cellular_component	ficolin-1-rich granule lumen

Functional Information from PDB Data

site_id	AC1
Number of Residues	15
Details	binding site for residue BZ7 C 301

Chain	Residue
C	THR1
C	ALA49
C	GLN53
X	ASP125
X	VAL127
X	SER129
X	GLN131
C	ALA20
C	SER21
C	ALA22
C	SER27
C	ALA28
C	VAL31
C	GLY47
C	CYS48

---

site_id	AC2
Number of Residues	16
Details	binding site for residue BZ7 D 301

Chain	Residue
D	THR1
D	ALA20
D	SER21
D	ALA22
D	SER27
D	ALA28
D	VAL31
D	SER46
D	GLY47
D	CYS48
D	ALA49
D	GLN53
S	ASP125
S	VAL127
S	SER129
S	GLN131

---

Functional Information from PROSITE/UniProt

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

Chain	Residue	Details
K	PHE9-ALA31
J	TYR7-ALA29
G	TYR6-ALA28
O	TYR5-ALA27
b	TYR5-ALA27
I	TYR3-ALA25
H	TYR8-ALA30

---

site_id	PS00854
Number of Residues	48
Details	PROTEASOME_BETA_1 Proteasome beta-type subunits signature. MAMkGknCVAIAADrrfgiqaqmvttdfq.KifpmgdrlyiglaGlaTD

Chain	Residue	Details
U	MET11-ASP58
C	LEU4-ASP51
T	ILE5-ASP52
B	ALA4-ASP51
O	LEU35-ASP82
S	LEU13-ASP60
A	MET4-ASP51
a	LEU12-ASP59

---

Functional Information from SwissProt/UniProt

site_id	SWS_FT_FI1
Number of Residues	2
Details	MOD_RES: Phosphotyrosine => ECO:0007744|PubMed:15592455

Chain	Residue	Details
W	TYR57
a	TYR57
S	SER134
X	SER34
X	SER40
X	SER134

---

site_id	SWS_FT_FI2
Number of Residues	2
Details	MOD_RES: N6-acetyllysine => ECO:0007744|PubMed:19608861

Chain	Residue	Details
U	LYS76
Y	LYS76
R	LYS102
R	LYS104
Q	LYS205
Q	LYS229

---

site_id	SWS_FT_FI3
Number of Residues	2
Details	MOD_RES: N6-acetyllysine => ECO:0007744|PubMed:19608861

Chain	Residue	Details
S	LYS176
X	LYS176
P	SER15
b	SER6
b	SER13
b	SER15

---

site_id	SWS_FT_FI4
Number of Residues	4
Details	CARBOHYD: O-linked (GlcNAc) serine => ECO:0000250

Chain	Residue	Details
S	SER30
S	SER181
X	SER30
X	SER181

---

site_id	SWS_FT_FI5
Number of Residues	4
Details	MOD_RES: N6-acetyllysine => ECO:0007744|PubMed:19608861

Chain	Residue	Details
P	LYS69
P	LYS170
b	LYS69
b	LYS170
L	LYS208

---

site_id	SWS_FT_FI6
Number of Residues	2
Details	MOD_RES: Phosphotyrosine => ECO:0007744|PubMed:23186163

Chain	Residue	Details
P	TYR75
b	TYR75

---

site_id	SWS_FT_FI7
Number of Residues	2
Details	MOD_RES: Phosphotyrosine => ECO:0000250|UniProtKB:P17220

Chain	Residue	Details
P	TYR120
b	TYR120

---