5MCO

CRYSTAL STRUCTURE OF BACE-1 IN COMPLEX WITH ACTIVE SITE INHIBITOR GRL-8234 AND EXOSITE PEPTIDE

External Resource: Annotation

Domain Annotation: SCOP2 Classification
Domain Annotation: ECOD Classification
Domain Annotation: CATH
Protein Family Annotation
Gene Ontology: Gene Product Annotation
InterPro: Protein Family Classification
Pharos: Disease Associations
Protein Modification Annotation

Domain Annotation: SCOP2 Classification SCOP2 Database Homepage

Chains	Type	Family Name	Domain Identifier	Family Identifier	Provenance Source (Version)
A	SCOP2B Superfamily	Acid proteases	8036280	3001059	SCOP2B (2022-06-29)

Domain Annotation: ECOD Classification ECOD Database Homepage

Chains	Family Name	Domain Identifier	Architecture	Possible Homology	Homology	Topology	Family	Provenance Source (Version)
A	Asp_C_1	e5mcoA2	A: beta barrels	X: cradle loop barrel	H: RIFT-related	T: acid protease	F: Asp_C_1	ECOD (1.6)
A	Asp_N	e5mcoA1	A: beta barrels	X: cradle loop barrel	H: RIFT-related	T: acid protease	F: Asp_N	ECOD (1.6)

Domain Annotation: CATH CATH Database Homepage

Chain	Domain	Class	Architecture	Topology	Homology	Provenance Source (Version)
A	2.40.70.10	Mainly Beta	Beta Barrel	Cathepsin D, subunit A	domain 1	CATH (4.3.0)

Protein Family Annotation Pfam Database Homepage

Chains	Accession	Name	Description	Comments	Source
A	PF00026	Eukaryotic aspartyl protease (Asp)	Eukaryotic aspartyl protease	-	Family

Gene Ontology: Gene Product Annotation Gene Ontology Database Homepage

Chains	Polymer	Molecular Function	Biological Process	Cellular Component
A	Beta-secretase 1	amide binding amyloid-beta binding binding peptide binding peptidase activity omega peptidase activity catalytic activity, acting on a protein threonine-type peptidase activity hydrolase activity beta-aspartyl-peptidase activity catalytic activity endopeptidase activity aspartic-type peptidase activity aspartic-type endopeptidase activity amide binding amyloid-beta binding binding peptide binding peptidase activity omega peptidase activity catalytic activity, acting on a protein threonine-type peptidase activity hydrolase activity beta-aspartyl-peptidase activity catalytic activity endopeptidase activity aspartic-type peptidase activity aspartic-type endopeptidase activity protein binding protein serine/threonine kinase binding kinase binding enzyme binding protein kinase binding	trans-synaptic signaling regulation of biological process regulation of signaling regulation of cellular process modulation of chemical synaptic transmission signaling biological regulation cell-cell signaling presynaptic modulation of chemical synaptic transmission chemical synaptic transmission cell communication synaptic signaling regulation of trans-synaptic signaling anterograde trans-synaptic signaling trans-synaptic signaling regulation of biological process regulation of signaling regulation of cellular process modulation of chemical synaptic transmission signaling biological regulation cell-cell signaling presynaptic modulation of chemical synaptic transmission chemical synaptic transmission cell communication synaptic signaling regulation of trans-synaptic signaling anterograde trans-synaptic signaling regulation of cell communication cellular process neuron apoptotic process positive regulation of programmed cell death regulation of apoptotic process positive regulation of biological process regulation of programmed cell death cell death positive regulation of apoptotic process apoptotic process positive regulation of neuron apoptotic process programmed cell death positive regulation of cellular process regulation of neuron apoptotic process startle response multicellular organismal process system process response to stimulus nervous system process regulation of response to external stimulus neuromuscular process negative regulation of response to stimulus negative regulation of biological process prepulse inhibition response to external stimulus regulation of response to stimulus negative regulation of response to external stimulus amyloid precursor protein catabolic process metabolic process primary metabolic process protein metabolic process macromolecule metabolic process amyloid precursor protein metabolic process cellular biosynthetic process cellular metabolic process signaling receptor ligand precursor processing gene expression macromolecule biosynthetic process protein maturation biosynthetic process proteolysis protein processing amyloid-beta metabolic process amide metabolic process detection of external stimulus detection of stimulus involved in sensory perception of pain detection of mechanical stimulus involved in sensory perception of pain response to mechanical stimulus sensory perception of pain detection of mechanical stimulus involved in sensory perception sensory perception of mechanical stimulus detection of abiotic stimulus detection of stimulus sensory perception detection of mechanical stimulus response to abiotic stimulus detection of stimulus involved in sensory perception cellular component organization cellular component organization or biogenesis supramolecular fiber organization amyloid fibril formation cellular response to stimulus cellular response to metal ion cellular response to chemical stimulus response to metal ion response to chemical cellular response to manganese ion response to manganese ion amyloid-beta formation response to copper ion cellular response to copper ion response to lead ion cellular response to nitrogen compound response to oxygen-containing compound response to nitrogen compound cellular response to amyloid-beta cellular response to oxygen-containing compound response to amyloid-beta membrane protein proteolysis membrane protein ectodomain proteolysis	membrane cellular anatomical entity somatodendritic compartment cell projection dendrite dendritic tree neuron projection plasma membrane bounded cell projection membrane-bounded organelle vesicle lumen intracellular anatomical structure Golgi-associated vesicle lumen Golgi apparatus intracellular vesicle membrane cellular anatomical entity somatodendritic compartment cell projection dendrite dendritic tree neuron projection plasma membrane bounded cell projection membrane-bounded organelle vesicle lumen intracellular anatomical structure Golgi-associated vesicle lumen Golgi apparatus intracellular vesicle membrane-enclosed lumen cytoplasmic vesicle lumen intracellular membrane-bounded organelle endomembrane system intracellular organelle lumen intracellular organelle cytoplasmic vesicle organelle lumen organelle cytoplasm Golgi-associated vesicle vesicle Golgi apparatus subcompartment organelle subcompartment trans-Golgi network endoplasmic reticulum lumen endoplasmic reticulum endosome recycling endosome endosome membrane cytoplasmic vesicle membrane bounding membrane of organelle vesicle membrane organelle membrane cell body neuronal cell body axon transport vesicle synapse presynapse synaptic vesicle cell junction secretory vesicle exocytic vesicle cell surface cell periphery plasma membrane membrane microdomain membrane raft late endosome multivesicular body lytic vacuole vacuole lysosome early endosome neuron to neuron synapse hippocampal mossy fiber to CA3 synapse
B	BACE-1 EXOSITE PEPTIDE	-	-	-

InterPro: Protein Family Classification InterPro Database Homepage

Chains	Accession	Name	Type
A	IPR009120	Beta-secretase BACE1	Family
A	IPR033121	Peptidase family A1 domain	Domain
A	IPR033874	Memapsin-like	Domain
A	IPR001461	Aspartic peptidase A1	Family
A	IPR009119	Beta-secretase BACE	Family
A	IPR021109	Aspartic peptidase domain superfamily	Homologous Superfamily
A	IPR001969	Aspartic peptidase, active site	Active Site

Pharos: Disease Associations Pharos Homepage Annotation

Chains	Drug Target	Associated Disease
A	Pharos: P56817	Alzheimer disease pancreatic intraductal papillary-mucinous carcinoma Presenile dementia subependymal giant cell astrocytoma atypical teratoid rhabdoid tumor lung cancer malignant pancreatic neoplasm ovarian cancer pancreatic intraductal papillary-mucinous neoplasm psoriasis toxic encephalopathy Crohn disease interstitial lung disease malignant ependymoma pancreatic ductal adenocarcinoma Alzheimer disease pancreatic intraductal papillary-mucinous carcinoma Presenile dementia subependymal giant cell astrocytoma atypical teratoid rhabdoid tumor lung cancer malignant pancreatic neoplasm ovarian cancer pancreatic intraductal papillary-mucinous neoplasm psoriasis toxic encephalopathy Crohn disease interstitial lung disease malignant ependymoma pancreatic ductal adenocarcinoma pancreatic intraductal papillary-mucinous neoplasm with low grade dysplasia schizophrenia amyloidosis dementia large cell medulloblastoma malignant mesothelioma osteosarcoma

Protein Modification Annotation

Modified Residue(s)
Chain	Residue(s)	Description
B	ACE	RESID: AA0041 , AA0042 , AA0043 , AA0044 , AA0045 , AA0046 , AA0049 , AA0050 , AA0051 , AA0052 , AA0053 , AA0054 , AA0354 PSI-MOD : N-acetyl-L-alanine MOD:00050 , N-acetyl-L-aspartic acid MOD:00051 , N-acetyl-L-cysteine MOD:00052 , N-acetyl-S-archeol-cysteine MOD:00897 , N-acetyl-L-glutamic acid MOD:00053 , N-acetyl-L-glutamine MOD:00054 , N-acetylglycine MOD:00055 , N-acetyl-L-methionine MOD:00058 , N-acetyl-L-proline MOD:00059 , N-acetyl-L-serine MOD:00060 , N,O-diacetylated L-serine MOD:00648 , N-acetyl-L-threonine MOD:00061 , N-acetyl-L-tyrosine MOD:00062 , N-acetyl-L-valine MOD:00063 , N2-acetyl-L-arginine MOD:00359

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.