6B7Z

Cryo-EM structure of human insulin degrading enzyme in complex with FAB H11 heavy chain and FAB H11 light chain

External Resource: Annotation

Domain Annotation: ECOD Classification
IMGT Antibody Annotation
SAbDab Antibody Annotation
Protein Family Annotation
Gene Ontology: Gene Product Annotation
InterPro: Protein Family Classification
Pharos: Disease Associations

Domain Annotation: ECOD Classification ECOD Database Homepage

Chains	Family Name	Domain Identifier	Architecture	Possible Homology	Homology	Topology	Family	Provenance Source (Version)
A	PF00675,PF05193	e6b7zA3	A: a+b two layers	X: LuxS, MPP, ThrRS/AlaRS common domain	H: LuxS, MPP, ThrRS/AlaRS common domain	T: LuxS/MPP-like metallohydrolase	F: PF00675,PF05193	ECOD (1.6)
A	PF05193,PF16187	e6b7zA1	A: a+b two layers	X: LuxS, MPP, ThrRS/AlaRS common domain	H: LuxS, MPP, ThrRS/AlaRS common domain	T: LuxS/MPP-like metallohydrolase	F: PF05193,PF16187	ECOD (1.6)
A	PF16187	e6b7zA4	A: a+b two layers	X: LuxS, MPP, ThrRS/AlaRS common domain	H: LuxS, MPP, ThrRS/AlaRS common domain	T: LuxS/MPP-like metallohydrolase	F: PF16187	ECOD (1.6)
A	PF22456	e6b7zA2	A: a+b two layers	X: LuxS, MPP, ThrRS/AlaRS common domain	H: LuxS, MPP, ThrRS/AlaRS common domain	T: LuxS/MPP-like metallohydrolase	F: PF22456	ECOD (1.6)
B	PF00675,PF05193	e6b7zB1	A: a+b two layers	X: LuxS, MPP, ThrRS/AlaRS common domain	H: LuxS, MPP, ThrRS/AlaRS common domain	T: LuxS/MPP-like metallohydrolase	F: PF00675,PF05193	ECOD (1.6)
B	PF05193,PF16187	e6b7zB2	A: a+b two layers	X: LuxS, MPP, ThrRS/AlaRS common domain	H: LuxS, MPP, ThrRS/AlaRS common domain	T: LuxS/MPP-like metallohydrolase	F: PF05193,PF16187	ECOD (1.6)
B	PF16187	e6b7zB3	A: a+b two layers	X: LuxS, MPP, ThrRS/AlaRS common domain	H: LuxS, MPP, ThrRS/AlaRS common domain	T: LuxS/MPP-like metallohydrolase	F: PF16187	ECOD (1.6)
B	PF22456	e6b7zB4	A: a+b two layers	X: LuxS, MPP, ThrRS/AlaRS common domain	H: LuxS, MPP, ThrRS/AlaRS common domain	T: LuxS/MPP-like metallohydrolase	F: PF22456	ECOD (1.6)
C	PF07654	e6b7zC2	A: beta sandwiches	X: Immunoglobulin-like beta-sandwich	H: Immunoglobulin-related	T: Immunoglobulin/Fibronectin type III/E set domains/PapD-like	F: PF07654	ECOD (1.6)
C	PF07686	e6b7zC1	A: beta sandwiches	X: Immunoglobulin-like beta-sandwich	H: Immunoglobulin-related	T: Immunoglobulin/Fibronectin type III/E set domains/PapD-like	F: PF07686	ECOD (1.6)
E	PF07654	e6b7zE2	A: beta sandwiches	X: Immunoglobulin-like beta-sandwich	H: Immunoglobulin-related	T: Immunoglobulin/Fibronectin type III/E set domains/PapD-like	F: PF07654	ECOD (1.6)
E	PF07686	e6b7zE1	A: beta sandwiches	X: Immunoglobulin-like beta-sandwich	H: Immunoglobulin-related	T: Immunoglobulin/Fibronectin type III/E set domains/PapD-like	F: PF07686	ECOD (1.6)
D	PF07654	e6b7zD2	A: beta sandwiches	X: Immunoglobulin-like beta-sandwich	H: Immunoglobulin-related	T: Immunoglobulin/Fibronectin type III/E set domains/PapD-like	F: PF07654	ECOD (1.6)
D	PF07686	e6b7zD1	A: beta sandwiches	X: Immunoglobulin-like beta-sandwich	H: Immunoglobulin-related	T: Immunoglobulin/Fibronectin type III/E set domains/PapD-like	F: PF07686	ECOD (1.6)
F	PF07654	e6b7zF1	A: beta sandwiches	X: Immunoglobulin-like beta-sandwich	H: Immunoglobulin-related	T: Immunoglobulin/Fibronectin type III/E set domains/PapD-like	F: PF07654	ECOD (1.6)
F	PF07686	e6b7zF2	A: beta sandwiches	X: Immunoglobulin-like beta-sandwich	H: Immunoglobulin-related	T: Immunoglobulin/Fibronectin type III/E set domains/PapD-like	F: PF07686	ECOD (1.6)

IMGT Antibody Annotation IMGT Database Homepage

Chain	Protein Name	Description	Organism Name	Gene Allele Name(s)	Domain Name(s)	Receptor Type	Receptor Description	Provenance Source
C, E	Fab H11	VH-CH1	Homo sapiens (human)	IGHV3-6601, IGHV3-6602, IGHV3-6604, IGHJ401, IGHJ402, IGHJ403, IGHG101, IGHG102, IGHG104, IGHG105	V-DOMAIN VH, C-DOMAIN CH1	IG	FAB-GAMMA-1_KAPPA	IMGT (202416-0)
D, F	Fab H11	L-KAPPA	Homo sapiens (human)	IGKV1-3901, IGKV1D-3901, IGKJ101, IGKC01	V-DOMAIN V-KAPPA, C-DOMAIN C-KAPPA	IG	FAB-GAMMA-1_KAPPA	IMGT (202416-0)

SAbDab Antibody Annotation SAbDab Database Homepage

Chain	Chain Class	Chain Subclass	Chain Type	Antigen Name(s)	Provenance Source
C, E	Heavy Chain	IGHV3	-	insulin-degrading enzyme	SAbDab (2024-04-26)
D, F	Light Chain	IGKV1	Kappa	insulin-degrading enzyme	SAbDab (2024-04-26)

Protein Family Annotation Pfam Database Homepage

Chains	Accession	Name	Description	Comments	Source
A, B	PF05193	Peptidase M16 inactive domain (Peptidase_M16_C)	Peptidase M16 inactive domain	Peptidase M16 consists of two structurally related domains. One is the active peptidase, whereas the other is inactive. The two domains hold the substrate like a clamp [1].	Domain
A, B	PF16187	Middle or third domain of peptidase_M16 (Peptidase_M16_M)	Middle or third domain of peptidase_M16	-	Family
A, B	PF00675	Insulinase (Peptidase family M16) (Peptidase_M16)	Insulinase (Peptidase family M16)	-	Family
C, E	PF07686	Immunoglobulin V-set domain (V-set)	Immunoglobulin V-set domain	This domain is found in antibodies as well as neural protein P0 and CTL4 amongst others.	Domain
C, E	PF07654	Immunoglobulin C1-set domain (C1-set)	Immunoglobulin C1-set domain	-	Domain
D, F	PF07686	Immunoglobulin V-set domain (V-set)	Immunoglobulin V-set domain	This domain is found in antibodies as well as neural protein P0 and CTL4 amongst others.	Domain
D, F	PF07654	Immunoglobulin C1-set domain (C1-set)	Immunoglobulin C1-set domain	-	Domain

Gene Ontology: Gene Product Annotation Gene Ontology Database Homepage

Chains	Polymer	Molecular Function	Biological Process	Cellular Component
A, B	Insulin-degrading enzyme	protein binding binding virus receptor activity exogenous protein binding amide binding peptide hormone binding hormone binding insulin binding peptidase activity catalytic activity, acting on a protein metalloendopeptidase activity hydrolase activity metallopeptidase activity catalytic activity protein binding binding virus receptor activity exogenous protein binding amide binding peptide hormone binding hormone binding insulin binding peptidase activity catalytic activity, acting on a protein metalloendopeptidase activity hydrolase activity metallopeptidase activity catalytic activity endopeptidase activity adenyl ribonucleotide binding nucleotide binding purine ribonucleotide binding purine ribonucleoside triphosphate binding nucleoside phosphate binding ion binding purine nucleotide binding organic cyclic compound binding anion binding adenyl nucleotide binding ATP binding heterocyclic compound binding carbohydrate derivative binding ribonucleotide binding small molecule binding identical protein binding protein homodimerization activity protein dimerization activity ubiquitin-modified protein reader activity modification-dependent protein binding protein-macromolecule adaptor activity ubiquitin-like protein reader activity molecular adaptor activity peptide binding cation binding transition metal ion binding zinc ion binding metal ion binding	organonitrogen compound metabolic process organic substance metabolic process amyloid-beta metabolic process metabolic process amide metabolic process cellular catabolic process catabolic process cellular metabolic process cellular process organic substance catabolic process peptide metabolic process peptide catabolic process multicellular organismal process amyloid-beta clearance by cellular catabolic process organonitrogen compound metabolic process organic substance metabolic process amyloid-beta metabolic process metabolic process amide metabolic process cellular catabolic process catabolic process cellular metabolic process cellular process organic substance catabolic process peptide metabolic process peptide catabolic process multicellular organismal process amyloid-beta clearance by cellular catabolic process amyloid-beta clearance primary metabolic process protein metabolic process macromolecule metabolic process insulin metabolic process organonitrogen compound catabolic process protein catabolic process macromolecule catabolic process proteolysis involved in protein catabolic process proteolysis positive regulation of protein metabolic process positive regulation of biological process regulation of primary metabolic process positive regulation of metabolic process positive regulation of macromolecule metabolic process regulation of biological process regulation of protein metabolic process biological regulation regulation of macromolecule metabolic process regulation of catabolic process positive regulation of protein catabolic process positive regulation of catabolic process regulation of metabolic process regulation of protein catabolic process cellular homeostasis homeostatic process ubiquitin recycling cellular response to stimulus cellular response to nitrogen compound response to organic substance regulation of cellular process response to stimulus signaling response to peptide hormone insulin receptor signaling pathway cell surface receptor protein tyrosine kinase signaling pathway cell communication cellular response to endogenous stimulus response to hormone cellular response to organic substance signal transduction enzyme-linked receptor protein signaling pathway cellular response to hormone stimulus cell surface receptor signaling pathway response to endogenous stimulus response to organonitrogen compound response to oxygen-containing compound cellular response to peptide hormone stimulus response to nitrogen compound cellular response to oxygen-containing compound cellular response to chemical stimulus cellular response to organonitrogen compound response to chemical response to insulin cellular response to insulin stimulus antigen processing and presentation immune system process antigen processing and presentation of endogenous peptide antigen antigen processing and presentation of peptide antigen via MHC class I antigen processing and presentation of peptide antigen antigen processing and presentation of endogenous antigen antigen processing and presentation of endogenous peptide antigen via MHC class I regulation of hormone levels regulation of biological quality hormone metabolic process hormone catabolic process bradykinin catabolic process aerobic respiration cellular respiration energy derivation by oxidation of organic compounds regulation of generation of precursor metabolites and energy regulation of cellular metabolic process generation of precursor metabolites and energy regulation of cellular respiration regulation of aerobic respiration regulation of protein binding positive regulation of molecular function regulation of molecular function positive regulation of protein binding regulation of binding positive regulation of binding insulin catabolic process	membrane-bounded organelle intracellular organelle intracellular anatomical structure mitochondrion organelle cytoplasm cellular anatomical entity intracellular membrane-bounded organelle cell periphery cell surface membrane plasma membrane external side of plasma membrane side of membrane membrane-bounded organelle intracellular organelle intracellular anatomical structure mitochondrion organelle cytoplasm cellular anatomical entity intracellular membrane-bounded organelle cell periphery cell surface membrane plasma membrane external side of plasma membrane side of membrane extracellular exosome extracellular vesicle extracellular organelle extracellular region extracellular space vesicle extracellular membrane-bounded organelle cytosol basal part of cell basal plasma membrane plasma membrane region basolateral plasma membrane peroxisome microbody peroxisomal matrix membrane-enclosed lumen intracellular organelle lumen organelle lumen microbody lumen nucleus
C, E	FAB H11 heavy chain	-	response to stimulus immune response immune system process adaptive immune response	cell periphery plasma membrane membrane cellular anatomical entity protein-containing complex immunoglobulin complex extracellular region
D, F	FAB H11 light chain	-	-	extracellular region cellular anatomical entity

InterPro: Protein Family Classification InterPro Database Homepage

Chains	Accession	Name	Type
A, B	IPR011249	Metalloenzyme, LuxS/M16 peptidase-like	Homologous Superfamily
A, B	IPR032632	Peptidase M16, middle/third domain	Domain
A, B	IPR001431	Peptidase M16, zinc-binding site	Binding Site
A, B	IPR007863	Peptidase M16, C-terminal	Domain
A, B	IPR011765	Peptidase M16, N-terminal	Domain
C, E	IPR003597	Immunoglobulin C1-set	Domain
C, E	IPR013783	Immunoglobulin-like fold	Homologous Superfamily
C, E	IPR036179	Immunoglobulin-like domain superfamily	Homologous Superfamily
C, E	IPR003599	Immunoglobulin subtype	Domain
C, E	IPR013106	Immunoglobulin V-set domain	Domain
C, E	IPR007110	Immunoglobulin-like domain	Domain
C, E	IPR003006	Immunoglobulin/major histocompatibility complex, conserved site	Conserved Site
D, F	IPR003597	Immunoglobulin C1-set	Domain
D, F	IPR013783	Immunoglobulin-like fold	Homologous Superfamily
D, F	IPR036179	Immunoglobulin-like domain superfamily	Homologous Superfamily
D, F	IPR003599	Immunoglobulin subtype	Domain
D, F	IPR013106	Immunoglobulin V-set domain	Domain
D, F	IPR007110	Immunoglobulin-like domain	Domain
D, F	IPR003006	Immunoglobulin/major histocompatibility complex, conserved site	Conserved Site

Pharos: Disease Associations Pharos Homepage Annotation

Chains	Drug Target	Associated Disease
A, B	Pharos: P14735	Alzheimer disease Presenile dementia atopic eczema large cell medulloblastoma malignant ependymoma osteosarcoma psoriasis atypical teratoid rhabdoid tumor glioblastoma lung cancer non-alcoholic fatty liver disease ovarian cancer schizophrenia amyotrophic lateral sclerosis dementia Alzheimer disease Presenile dementia atopic eczema large cell medulloblastoma malignant ependymoma osteosarcoma psoriasis atypical teratoid rhabdoid tumor glioblastoma lung cancer non-alcoholic fatty liver disease ovarian cancer schizophrenia amyotrophic lateral sclerosis dementia invasive ductal breast carcinoma lymphoplasmacytic lymphoma non-small cell lung carcinoma

RCSB PDB Core Operations are funded by the U.S. National Science Foundation (DBI-2321666), the US Department of Energy (DE-SC0019749), and the National Cancer Institute, National Institute of Allergy and Infectious Diseases, and National Institute of General Medical Sciences of the National Institutes of Health under grant R01GM133198.