4LTE

Structure of Cysteine-free Human Insulin Degrading Enzyme in Complex with Macrocyclic Inhibitor

External Resource: Annotation

Domain Annotation: ECOD Classification
Domain Annotation: CATH
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	Peptidase_M16_M_C	e4lteA4	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: Peptidase_M16_M_C	ECOD (1.6)
A	Peptidase_M16_M_N	e4lteA2	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: Peptidase_M16_M_N	ECOD (1.6)
A	Peptidase_M16_C_2	e4lteA3	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: Peptidase_M16_C_2	ECOD (1.6)
A	Peptidase_M16	e4lteA1	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: Peptidase_M16	ECOD (1.6)
B	Peptidase_M16_M_C	e4lteB4	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: Peptidase_M16_M_C	ECOD (1.6)
B	Peptidase_M16_M_N	e4lteB2	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: Peptidase_M16_M_N	ECOD (1.6)
B	Peptidase_M16_C_2	e4lteB3	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: Peptidase_M16_C_2	ECOD (1.6)
B	Peptidase_M16	e4lteB1	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: Peptidase_M16	ECOD (1.6)

Domain Annotation: CATH CATH Database Homepage

Chain	Domain	Class	Architecture	Topology	Homology	Provenance Source (Version)
A	3.30.830.10	Alpha Beta	2-Layer Sandwich	Cytochrome Bc1 Complex	Chain A, domain 1	CATH (4.3.0)
B	3.30.830.10	Alpha Beta	2-Layer Sandwich	Cytochrome Bc1 Complex	Chain A, domain 1	CATH (4.3.0)

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

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 peptide binding cation binding transition metal ion binding zinc ion binding metal ion binding	amyloid-beta metabolic process metabolic process cellular process amide metabolic process cellular catabolic process 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 amyloid-beta metabolic process metabolic process cellular process amide metabolic process cellular catabolic process 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 protein catabolic process macromolecule catabolic process proteolysis involved in protein catabolic process proteolysis regulation of cellular process 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 positive regulation of cellular 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 nitrogen compound cellular response to stimulus 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 signal transduction enzyme-linked receptor protein signaling pathway cellular response to hormone stimulus cell surface receptor signaling pathway response to endogenous stimulus 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 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 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 cellular anatomical structure intracellular anatomical structure mitochondrion organelle cytoplasm intracellular membrane-bounded organelle cell periphery cell surface membrane plasma membrane external side of plasma membrane side of membrane membrane-bounded organelle intracellular organelle cellular anatomical structure intracellular anatomical structure mitochondrion organelle cytoplasm 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 [auth M], D [auth N]	Macrocyclic Inhibitor	-	-	-

InterPro: Protein Family Classification InterPro Database Homepage

Chains	Accession	Name	Type
A, B	IPR011249	Metalloenzyme, LuxS/M16 peptidase-like	Homologous Superfamily
A, B	IPR050626	Peptidase M16	Family
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

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 R01GM157729.