5WOB

Crystal Structure Analysis of Fab1-Bound Human Insulin Degrading Enzyme (IDE) in Complex with Insulin

Replaces:  4Q5Z

Functional Information from GO Data

Chain	GOid	namespace	contents
a	0005179	molecular_function	hormone activity
a	0005576	cellular_component	extracellular region
A	0001618	molecular_function	virus receptor activity
A	0004175	molecular_function	endopeptidase activity
A	0004222	molecular_function	metalloendopeptidase activity
A	0005515	molecular_function	protein binding
A	0005524	molecular_function	ATP binding
A	0005576	cellular_component	extracellular region
A	0005615	cellular_component	extracellular space
A	0005634	cellular_component	nucleus
A	0005737	cellular_component	cytoplasm
A	0005739	cellular_component	mitochondrion
A	0005777	cellular_component	peroxisome
A	0005782	cellular_component	peroxisomal matrix
A	0005829	cellular_component	cytosol
A	0005886	cellular_component	plasma membrane
A	0006508	biological_process	proteolysis
A	0008237	molecular_function	metallopeptidase activity
A	0008270	molecular_function	zinc ion binding
A	0008286	biological_process	insulin receptor signaling pathway
A	0009897	cellular_component	external side of plasma membrane
A	0009986	cellular_component	cell surface
A	0010815	biological_process	bradykinin catabolic process
A	0010992	biological_process	ubiquitin recycling
A	0016323	cellular_component	basolateral plasma membrane
A	0019885	biological_process	antigen processing and presentation of endogenous peptide antigen via MHC class I
A	0030163	biological_process	protein catabolic process
A	0032092	biological_process	positive regulation of protein binding
A	0042277	molecular_function	peptide binding
A	0042447	biological_process	hormone catabolic process
A	0042803	molecular_function	protein homodimerization activity
A	0043171	biological_process	peptide catabolic process
A	0043559	molecular_function	insulin binding
A	0045732	biological_process	positive regulation of protein catabolic process
A	0046718	biological_process	symbiont entry into host cell
A	0046872	molecular_function	metal ion binding
A	0050435	biological_process	amyloid-beta metabolic process
A	0051603	biological_process	proteolysis involved in protein catabolic process
A	0070062	cellular_component	extracellular exosome
A	0097242	biological_process	amyloid-beta clearance
A	0150094	biological_process	amyloid-beta clearance by cellular catabolic process
A	1901142	biological_process	insulin metabolic process
A	1901143	biological_process	insulin catabolic process
A	1903715	biological_process	regulation of aerobic respiration
b	0005179	molecular_function	hormone activity
b	0005576	cellular_component	extracellular region
B	0001618	molecular_function	virus receptor activity
B	0004175	molecular_function	endopeptidase activity
B	0004222	molecular_function	metalloendopeptidase activity
B	0005515	molecular_function	protein binding
B	0005524	molecular_function	ATP binding
B	0005576	cellular_component	extracellular region
B	0005615	cellular_component	extracellular space
B	0005634	cellular_component	nucleus
B	0005737	cellular_component	cytoplasm
B	0005739	cellular_component	mitochondrion
B	0005777	cellular_component	peroxisome
B	0005782	cellular_component	peroxisomal matrix
B	0005829	cellular_component	cytosol
B	0005886	cellular_component	plasma membrane
B	0006508	biological_process	proteolysis
B	0008237	molecular_function	metallopeptidase activity
B	0008270	molecular_function	zinc ion binding
B	0008286	biological_process	insulin receptor signaling pathway
B	0009897	cellular_component	external side of plasma membrane
B	0009986	cellular_component	cell surface
B	0010815	biological_process	bradykinin catabolic process
B	0010992	biological_process	ubiquitin recycling
B	0016323	cellular_component	basolateral plasma membrane
B	0019885	biological_process	antigen processing and presentation of endogenous peptide antigen via MHC class I
B	0030163	biological_process	protein catabolic process
B	0032092	biological_process	positive regulation of protein binding
B	0042277	molecular_function	peptide binding
B	0042447	biological_process	hormone catabolic process
B	0042803	molecular_function	protein homodimerization activity
B	0043171	biological_process	peptide catabolic process
B	0043559	molecular_function	insulin binding
B	0045732	biological_process	positive regulation of protein catabolic process
B	0046718	biological_process	symbiont entry into host cell
B	0046872	molecular_function	metal ion binding
B	0050435	biological_process	amyloid-beta metabolic process
B	0051603	biological_process	proteolysis involved in protein catabolic process
B	0070062	cellular_component	extracellular exosome
B	0097242	biological_process	amyloid-beta clearance
B	0150094	biological_process	amyloid-beta clearance by cellular catabolic process
B	1901142	biological_process	insulin metabolic process
B	1901143	biological_process	insulin catabolic process
B	1903715	biological_process	regulation of aerobic respiration
c	0005179	molecular_function	hormone activity
c	0005576	cellular_component	extracellular region
C	0001618	molecular_function	virus receptor activity
C	0004175	molecular_function	endopeptidase activity
C	0004222	molecular_function	metalloendopeptidase activity
C	0005515	molecular_function	protein binding
C	0005524	molecular_function	ATP binding
C	0005576	cellular_component	extracellular region
C	0005615	cellular_component	extracellular space
C	0005634	cellular_component	nucleus
C	0005737	cellular_component	cytoplasm
C	0005739	cellular_component	mitochondrion
C	0005777	cellular_component	peroxisome
C	0005782	cellular_component	peroxisomal matrix
C	0005829	cellular_component	cytosol
C	0005886	cellular_component	plasma membrane
C	0006508	biological_process	proteolysis
C	0008237	molecular_function	metallopeptidase activity
C	0008270	molecular_function	zinc ion binding
C	0008286	biological_process	insulin receptor signaling pathway
C	0009897	cellular_component	external side of plasma membrane
C	0009986	cellular_component	cell surface
C	0010815	biological_process	bradykinin catabolic process
C	0010992	biological_process	ubiquitin recycling
C	0016323	cellular_component	basolateral plasma membrane
C	0019885	biological_process	antigen processing and presentation of endogenous peptide antigen via MHC class I
C	0030163	biological_process	protein catabolic process
C	0032092	biological_process	positive regulation of protein binding
C	0042277	molecular_function	peptide binding
C	0042447	biological_process	hormone catabolic process
C	0042803	molecular_function	protein homodimerization activity
C	0043171	biological_process	peptide catabolic process
C	0043559	molecular_function	insulin binding
C	0045732	biological_process	positive regulation of protein catabolic process
C	0046718	biological_process	symbiont entry into host cell
C	0046872	molecular_function	metal ion binding
C	0050435	biological_process	amyloid-beta metabolic process
C	0051603	biological_process	proteolysis involved in protein catabolic process
C	0070062	cellular_component	extracellular exosome
C	0097242	biological_process	amyloid-beta clearance
C	0150094	biological_process	amyloid-beta clearance by cellular catabolic process
C	1901142	biological_process	insulin metabolic process
C	1901143	biological_process	insulin catabolic process
C	1903715	biological_process	regulation of aerobic respiration
d	0005179	molecular_function	hormone activity
d	0005576	cellular_component	extracellular region
D	0001618	molecular_function	virus receptor activity
D	0004175	molecular_function	endopeptidase activity
D	0004222	molecular_function	metalloendopeptidase activity
D	0005515	molecular_function	protein binding
D	0005524	molecular_function	ATP binding
D	0005576	cellular_component	extracellular region
D	0005615	cellular_component	extracellular space
D	0005634	cellular_component	nucleus
D	0005737	cellular_component	cytoplasm
D	0005739	cellular_component	mitochondrion
D	0005777	cellular_component	peroxisome
D	0005782	cellular_component	peroxisomal matrix
D	0005829	cellular_component	cytosol
D	0005886	cellular_component	plasma membrane
D	0006508	biological_process	proteolysis
D	0008237	molecular_function	metallopeptidase activity
D	0008270	molecular_function	zinc ion binding
D	0008286	biological_process	insulin receptor signaling pathway
D	0009897	cellular_component	external side of plasma membrane
D	0009986	cellular_component	cell surface
D	0010815	biological_process	bradykinin catabolic process
D	0010992	biological_process	ubiquitin recycling
D	0016323	cellular_component	basolateral plasma membrane
D	0019885	biological_process	antigen processing and presentation of endogenous peptide antigen via MHC class I
D	0030163	biological_process	protein catabolic process
D	0032092	biological_process	positive regulation of protein binding
D	0042277	molecular_function	peptide binding
D	0042447	biological_process	hormone catabolic process
D	0042803	molecular_function	protein homodimerization activity
D	0043171	biological_process	peptide catabolic process
D	0043559	molecular_function	insulin binding
D	0045732	biological_process	positive regulation of protein catabolic process
D	0046718	biological_process	symbiont entry into host cell
D	0046872	molecular_function	metal ion binding
D	0050435	biological_process	amyloid-beta metabolic process
D	0051603	biological_process	proteolysis involved in protein catabolic process
D	0070062	cellular_component	extracellular exosome
D	0097242	biological_process	amyloid-beta clearance
D	0150094	biological_process	amyloid-beta clearance by cellular catabolic process
D	1901142	biological_process	insulin metabolic process
D	1901143	biological_process	insulin catabolic process
D	1903715	biological_process	regulation of aerobic respiration
e	0005179	molecular_function	hormone activity
e	0005576	cellular_component	extracellular region
E	0001618	molecular_function	virus receptor activity
E	0004175	molecular_function	endopeptidase activity
E	0004222	molecular_function	metalloendopeptidase activity
E	0005515	molecular_function	protein binding
E	0005524	molecular_function	ATP binding
E	0005576	cellular_component	extracellular region
E	0005615	cellular_component	extracellular space
E	0005634	cellular_component	nucleus
E	0005737	cellular_component	cytoplasm
E	0005739	cellular_component	mitochondrion
E	0005777	cellular_component	peroxisome
E	0005782	cellular_component	peroxisomal matrix
E	0005829	cellular_component	cytosol
E	0005886	cellular_component	plasma membrane
E	0006508	biological_process	proteolysis
E	0008237	molecular_function	metallopeptidase activity
E	0008270	molecular_function	zinc ion binding
E	0008286	biological_process	insulin receptor signaling pathway
E	0009897	cellular_component	external side of plasma membrane
E	0009986	cellular_component	cell surface
E	0010815	biological_process	bradykinin catabolic process
E	0010992	biological_process	ubiquitin recycling
E	0016323	cellular_component	basolateral plasma membrane
E	0019885	biological_process	antigen processing and presentation of endogenous peptide antigen via MHC class I
E	0030163	biological_process	protein catabolic process
E	0032092	biological_process	positive regulation of protein binding
E	0042277	molecular_function	peptide binding
E	0042447	biological_process	hormone catabolic process
E	0042803	molecular_function	protein homodimerization activity
E	0043171	biological_process	peptide catabolic process
E	0043559	molecular_function	insulin binding
E	0045732	biological_process	positive regulation of protein catabolic process
E	0046718	biological_process	symbiont entry into host cell
E	0046872	molecular_function	metal ion binding
E	0050435	biological_process	amyloid-beta metabolic process
E	0051603	biological_process	proteolysis involved in protein catabolic process
E	0070062	cellular_component	extracellular exosome
E	0097242	biological_process	amyloid-beta clearance
E	0150094	biological_process	amyloid-beta clearance by cellular catabolic process
E	1901142	biological_process	insulin metabolic process
E	1901143	biological_process	insulin catabolic process
E	1903715	biological_process	regulation of aerobic respiration
f	0005179	molecular_function	hormone activity
f	0005576	cellular_component	extracellular region
F	0001618	molecular_function	virus receptor activity
F	0004175	molecular_function	endopeptidase activity
F	0004222	molecular_function	metalloendopeptidase activity
F	0005515	molecular_function	protein binding
F	0005524	molecular_function	ATP binding
F	0005576	cellular_component	extracellular region
F	0005615	cellular_component	extracellular space
F	0005634	cellular_component	nucleus
F	0005737	cellular_component	cytoplasm
F	0005739	cellular_component	mitochondrion
F	0005777	cellular_component	peroxisome
F	0005782	cellular_component	peroxisomal matrix
F	0005829	cellular_component	cytosol
F	0005886	cellular_component	plasma membrane
F	0006508	biological_process	proteolysis
F	0008237	molecular_function	metallopeptidase activity
F	0008270	molecular_function	zinc ion binding
F	0008286	biological_process	insulin receptor signaling pathway
F	0009897	cellular_component	external side of plasma membrane
F	0009986	cellular_component	cell surface
F	0010815	biological_process	bradykinin catabolic process
F	0010992	biological_process	ubiquitin recycling
F	0016323	cellular_component	basolateral plasma membrane
F	0019885	biological_process	antigen processing and presentation of endogenous peptide antigen via MHC class I
F	0030163	biological_process	protein catabolic process
F	0032092	biological_process	positive regulation of protein binding
F	0042277	molecular_function	peptide binding
F	0042447	biological_process	hormone catabolic process
F	0042803	molecular_function	protein homodimerization activity
F	0043171	biological_process	peptide catabolic process
F	0043559	molecular_function	insulin binding
F	0045732	biological_process	positive regulation of protein catabolic process
F	0046718	biological_process	symbiont entry into host cell
F	0046872	molecular_function	metal ion binding
F	0050435	biological_process	amyloid-beta metabolic process
F	0051603	biological_process	proteolysis involved in protein catabolic process
F	0070062	cellular_component	extracellular exosome
F	0097242	biological_process	amyloid-beta clearance
F	0150094	biological_process	amyloid-beta clearance by cellular catabolic process
F	1901142	biological_process	insulin metabolic process
F	1901143	biological_process	insulin catabolic process
F	1903715	biological_process	regulation of aerobic respiration
g	0005179	molecular_function	hormone activity
g	0005576	cellular_component	extracellular region
G	0001618	molecular_function	virus receptor activity
G	0004175	molecular_function	endopeptidase activity
G	0004222	molecular_function	metalloendopeptidase activity
G	0005515	molecular_function	protein binding
G	0005524	molecular_function	ATP binding
G	0005576	cellular_component	extracellular region
G	0005615	cellular_component	extracellular space
G	0005634	cellular_component	nucleus
G	0005737	cellular_component	cytoplasm
G	0005739	cellular_component	mitochondrion
G	0005777	cellular_component	peroxisome
G	0005782	cellular_component	peroxisomal matrix
G	0005829	cellular_component	cytosol
G	0005886	cellular_component	plasma membrane
G	0006508	biological_process	proteolysis
G	0008237	molecular_function	metallopeptidase activity
G	0008270	molecular_function	zinc ion binding
G	0008286	biological_process	insulin receptor signaling pathway
G	0009897	cellular_component	external side of plasma membrane
G	0009986	cellular_component	cell surface
G	0010815	biological_process	bradykinin catabolic process
G	0010992	biological_process	ubiquitin recycling
G	0016323	cellular_component	basolateral plasma membrane
G	0019885	biological_process	antigen processing and presentation of endogenous peptide antigen via MHC class I
G	0030163	biological_process	protein catabolic process
G	0032092	biological_process	positive regulation of protein binding
G	0042277	molecular_function	peptide binding
G	0042447	biological_process	hormone catabolic process
G	0042803	molecular_function	protein homodimerization activity
G	0043171	biological_process	peptide catabolic process
G	0043559	molecular_function	insulin binding
G	0045732	biological_process	positive regulation of protein catabolic process
G	0046718	biological_process	symbiont entry into host cell
G	0046872	molecular_function	metal ion binding
G	0050435	biological_process	amyloid-beta metabolic process
G	0051603	biological_process	proteolysis involved in protein catabolic process
G	0070062	cellular_component	extracellular exosome
G	0097242	biological_process	amyloid-beta clearance
G	0150094	biological_process	amyloid-beta clearance by cellular catabolic process
G	1901142	biological_process	insulin metabolic process
G	1901143	biological_process	insulin catabolic process
G	1903715	biological_process	regulation of aerobic respiration
h	0005179	molecular_function	hormone activity
h	0005576	cellular_component	extracellular region
H	0001618	molecular_function	virus receptor activity
H	0004175	molecular_function	endopeptidase activity
H	0004222	molecular_function	metalloendopeptidase activity
H	0005515	molecular_function	protein binding
H	0005524	molecular_function	ATP binding
H	0005576	cellular_component	extracellular region
H	0005615	cellular_component	extracellular space
H	0005634	cellular_component	nucleus
H	0005737	cellular_component	cytoplasm
H	0005739	cellular_component	mitochondrion
H	0005777	cellular_component	peroxisome
H	0005782	cellular_component	peroxisomal matrix
H	0005829	cellular_component	cytosol
H	0005886	cellular_component	plasma membrane
H	0006508	biological_process	proteolysis
H	0008237	molecular_function	metallopeptidase activity
H	0008270	molecular_function	zinc ion binding
H	0008286	biological_process	insulin receptor signaling pathway
H	0009897	cellular_component	external side of plasma membrane
H	0009986	cellular_component	cell surface
H	0010815	biological_process	bradykinin catabolic process
H	0010992	biological_process	ubiquitin recycling
H	0016323	cellular_component	basolateral plasma membrane
H	0019885	biological_process	antigen processing and presentation of endogenous peptide antigen via MHC class I
H	0030163	biological_process	protein catabolic process
H	0032092	biological_process	positive regulation of protein binding
H	0042277	molecular_function	peptide binding
H	0042447	biological_process	hormone catabolic process
H	0042803	molecular_function	protein homodimerization activity
H	0043171	biological_process	peptide catabolic process
H	0043559	molecular_function	insulin binding
H	0045732	biological_process	positive regulation of protein catabolic process
H	0046718	biological_process	symbiont entry into host cell
H	0046872	molecular_function	metal ion binding
H	0050435	biological_process	amyloid-beta metabolic process
H	0051603	biological_process	proteolysis involved in protein catabolic process
H	0070062	cellular_component	extracellular exosome
H	0097242	biological_process	amyloid-beta clearance
H	0150094	biological_process	amyloid-beta clearance by cellular catabolic process
H	1901142	biological_process	insulin metabolic process
H	1901143	biological_process	insulin catabolic process
H	1903715	biological_process	regulation of aerobic respiration

Functional Information from PDB Data

site_id	AC1
Number of Residues	5
Details	binding site for residue ZN A 1101

Chain	Residue
A	HIS108
A	HIS112
A	GLU189
a	SER12
a	TYR14

---

site_id	AC2
Number of Residues	3
Details	binding site for residue ZN B 2001

Chain	Residue
B	HIS108
B	HIS112
B	GLU189

---

site_id	AC3
Number of Residues	4
Details	binding site for residue ZN C 1101

Chain	Residue
C	HIS112
C	GLU189
c	TYR14
C	HIS108

---

site_id	AC4
Number of Residues	3
Details	binding site for residue ZN D 2001

Chain	Residue
D	HIS108
D	HIS112
D	GLU189

---

site_id	AC5
Number of Residues	3
Details	binding site for residue ZN E 2001

Chain	Residue
E	HIS108
E	HIS112
E	GLU189

---

site_id	AC6
Number of Residues	3
Details	binding site for residue ZN F 1101

Chain	Residue
F	HIS108
F	HIS112
F	GLU189

---

site_id	AC7
Number of Residues	2
Details	binding site for residue ZN G 2001

Chain	Residue
G	HIS108
G	HIS112

---

site_id	AC8
Number of Residues	3
Details	binding site for residue ZN H 1101

Chain	Residue
H	HIS108
H	HIS112
H	GLU189

---

Functional Information from PROSITE/UniProt

site_id	PS00262
Number of Residues	15
Details	INSULIN Insulin family signature. CCTSiCSlyqLenyC

Chain	Residue	Details
a	CYS6-CYS20

---

site_id	PS00290
Number of Residues	7
Details	IG_MHC Immunoglobulins and major histocompatibility complex proteins signature. YACEVTH

Chain	Residue	Details
N	TYR193-HIS199
I	TYR210-HIS216

---

Functional Information from SwissProt/UniProt

site_id	SWS_FT_FI1
Number of Residues	8
Details	ACT_SITE: Proton acceptor => ECO:0000255|PROSITE-ProRule:PRU10096, ECO:0000305|PubMed:10684867, ECO:0000305|PubMed:17051221, ECO:0000305|PubMed:19321446, ECO:0000305|PubMed:23922390

Chain	Residue	Details
A	GLN111
B	GLN111
C	GLN111
D	GLN111
E	GLN111
F	GLN111
G	GLN111
H	GLN111

---

site_id	SWS_FT_FI2
Number of Residues	24
Details	BINDING: BINDING => ECO:0000255|PROSITE-ProRule:PRU10096, ECO:0000269|PubMed:17051221, ECO:0000269|PubMed:17613531, ECO:0000269|PubMed:18986166, ECO:0000269|PubMed:19321446, ECO:0007744|PDB:2G54, ECO:0007744|PDB:2JG4, ECO:0007744|PDB:3CWW, ECO:0007744|PDB:3N56, ECO:0007744|PDB:3N57

Chain	Residue	Details
A	HIS108
D	HIS108
D	HIS112
D	GLU189
E	HIS108
E	HIS112
E	GLU189
F	HIS108
F	HIS112
F	GLU189
G	HIS108
A	HIS112
G	HIS112
G	GLU189
H	HIS108
H	HIS112
H	GLU189
A	GLU189
B	HIS108
B	HIS112
B	GLU189
C	HIS108
C	HIS112
C	GLU189

---

site_id	SWS_FT_FI3
Number of Residues	8
Details	BINDING: in the exosite

Chain	Residue	Details
A	HIS336
B	HIS336
C	HIS336
D	HIS336
E	HIS336
F	HIS336
G	HIS336
H	HIS336

---

site_id	SWS_FT_FI4
Number of Residues	8
Details	BINDING: BINDING => ECO:0000269|PubMed:18986166

Chain	Residue	Details
A	LEU359
B	LEU359
C	LEU359
D	LEU359
E	LEU359
F	LEU359
G	LEU359
H	LEU359

---

site_id	SWS_FT_FI5
Number of Residues	16
Details	BINDING: BINDING => ECO:0000250|UniProtKB:P35559

Chain	Residue	Details
A	ARG429
E	ASP895
F	ARG429
F	ASP895
G	ARG429
G	ASP895
H	ARG429
H	ASP895
A	ASP895
B	ARG429
B	ASP895
C	ARG429
C	ASP895
D	ARG429
D	ASP895
E	ARG429

---

site_id	SWS_FT_FI6
Number of Residues	16
Details	MOD_RES: N6-succinyllysine => ECO:0000250|UniProtKB:Q9JHR7

Chain	Residue	Details
A	LYS192
E	LYS697
F	LYS192
F	LYS697
G	LYS192
G	LYS697
H	LYS192
H	LYS697
A	LYS697
B	LYS192
B	LYS697
C	LYS192
C	LYS697
D	LYS192
D	LYS697
E	LYS192

---