4OJF | pdb_00004ojf

Humanised 3D6 Fab complexed to amyloid beta 1-8

External Resource: Annotation

Domain Annotation: ECOD Classification
Domain Annotation: CATH
IMGT Antibody Annotation
SAbDab Antibody Annotation
Thera-SAbDab Antibody 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 [auth H]	V-set_8	e4ojfH2	A: beta sandwiches	X: Immunoglobulin-like beta-sandwich	H: Immunoglobulin-related	T: Immunoglobulin/Fibronectin type III/E set domains/PapD-like	F: V-set_8	ECOD (1.6)
A [auth H]	C1-set_1	e4ojfH1	A: beta sandwiches	X: Immunoglobulin-like beta-sandwich	H: Immunoglobulin-related	T: Immunoglobulin/Fibronectin type III/E set domains/PapD-like	F: C1-set_1	ECOD (1.6)
B [auth L]	C1-set_4	e4ojfL1	A: beta sandwiches	X: Immunoglobulin-like beta-sandwich	H: Immunoglobulin-related	T: Immunoglobulin/Fibronectin type III/E set domains/PapD-like	F: C1-set_4	ECOD (1.6)
B [auth L]	V-set	e4ojfL2	A: beta sandwiches	X: Immunoglobulin-like beta-sandwich	H: Immunoglobulin-related	T: Immunoglobulin/Fibronectin type III/E set domains/PapD-like	F: V-set	ECOD (1.6)

Domain Annotation: CATH CATH Database Homepage

Chain	Domain	Class	Architecture	Topology	Homology	Provenance Source (Version)
A [auth H]	2.60.40.10	Mainly Beta	Sandwich	Immunoglobulin-like	Immunoglobulins	CATH (4.3.0)
B [auth L]	2.60.40.10	Mainly Beta	Sandwich	Immunoglobulin-like	Immunoglobulins	CATH (4.3.0)

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
A [auth H]	anti-APP (amyloid beta A4 precursor protein) Abeta	VH-CH1	Humanized (humanized)	IGHV3-701, IGHV3-702, IGHV3-2303, IGHV3-703, IGHJ401, IGHJ402, IGHJ403, IGHG101, IGHG102, IGHG104	V-DOMAIN VH, C-DOMAIN CH1	IG	FAB-GAMMA-1_KAPPA	IMGT (202510-0)
B [auth L]	anti-APP (amyloid beta A4 precursor protein) Abeta	L-KAPPA	Humanized (humanized)	IGKV2-2902, IGKV2-3001, IGKV2D-3001, IGKV2-2903, IGKV2-3002, IGKJ101, IGKC*01	V-DOMAIN V-KAPPA, C-DOMAIN C-KAPPA	IG	FAB-GAMMA-1_KAPPA	IMGT (202510-0)

SAbDab Antibody Annotation SAbDab Database Homepage

Chain	Chain Class	Chain Subclass	Chain Type	Antigen Name(s)	Provenance Source
A [auth H]	Heavy Chain	IGHV3	-	amyloid beta a4 protein	SAbDab (2025-03-21)
B [auth L]	Light Chain	IGKV2	Kappa	amyloid beta a4 protein	SAbDab (2025-03-21)

Thera-SAbDab Antibody Annotation Thera-SAbDab Database Homepage

Chain	Name	Target	Provenance Source
A [auth H]	Bapineuzumab	APP	Therapeutic SAbDab (2025-03-21)
B [auth L]	Bapineuzumab	APP	Therapeutic SAbDab (2025-03-21)

Gene Ontology: Gene Product Annotation Gene Ontology Database Homepage

Chains	Polymer	Molecular Function	Biological Process	Cellular Component
A [auth H]	Humanised 3D6 Fab Heavy Chain	-	-	-
B [auth L]	Humanised 3D6 Fab Light Chain	-	-	-
C [auth A]	Amyloid beta A4 protein	DNA binding binding nucleic acid binding protein binding signaling receptor binding cation binding transition metal ion binding ion binding metal ion binding small molecule binding PTB domain binding protein domain specific binding identical protein binding molecular transducer activity DNA binding binding nucleic acid binding protein binding signaling receptor binding cation binding transition metal ion binding ion binding metal ion binding small molecule binding PTB domain binding protein domain specific binding identical protein binding molecular transducer activity molecular function activator activity signaling receptor activity molecular function regulator activity signaling receptor regulator activity receptor ligand activity signaling receptor activator activity sequence-specific DNA binding double-stranded DNA binding RNA polymerase II transcription regulatory region sequence-specific DNA binding cis-regulatory region sequence-specific DNA binding sequence-specific double-stranded DNA binding transcription cis-regulatory region binding transcription regulatory region nucleic acid binding RNA polymerase II cis-regulatory region sequence-specific DNA binding enzyme regulator activity peptidase activity peptidase regulator activity catalytic activity, acting on a protein serine hydrolase activity serine-type endopeptidase inhibitor activity hydrolase activity enzyme inhibitor activity peptidase inhibitor activity endopeptidase regulator activity endopeptidase inhibitor activity molecular function inhibitor activity serine-type peptidase activity serine-type endopeptidase activity catalytic activity endopeptidase activity protein serine/threonine kinase binding kinase binding enzyme binding protein kinase binding heparin binding glycosaminoglycan binding carbohydrate derivative binding sulfur compound binding	negative regulation of long-term synaptic potentiation positive regulation of cell communication regulation of cellular process modulation of chemical synaptic transmission signaling positive regulation of biological process negative regulation of biological process cell communication long-term synaptic potentiation synaptic signaling regulation of biological quality positive regulation of cellular process regulation of synaptic plasticity trans-synaptic signaling negative regulation of long-term synaptic potentiation positive regulation of cell communication regulation of cellular process modulation of chemical synaptic transmission signaling positive regulation of biological process negative regulation of biological process cell communication long-term synaptic potentiation synaptic signaling regulation of biological quality positive regulation of cellular process regulation of synaptic plasticity trans-synaptic signaling regulation of biological process regulation of signaling biological regulation cell-cell signaling positive regulation of synaptic transmission chemical synaptic transmission regulation of trans-synaptic signaling anterograde trans-synaptic signaling regulation of long-term synaptic potentiation regulation of cell communication cellular process positive regulation of signaling regulation of synapse structure or activity cellular response to stimulus multicellular organismal process regulation of postsynaptic membrane potential system process response to stimulus regulation of system process regulation of signal transduction chemical synaptic transmission, postsynaptic modulation of excitatory postsynaptic potential regulation of multicellular organismal process signal transduction cell surface receptor signaling pathway nervous system process regulation of nervous system process regulation of response to stimulus excitatory postsynaptic potential regulation of membrane potential positive regulation of signal transduction intracellular signal transduction positive regulation of response to stimulus regulation of intracellular signal transduction intracellular signaling cassette regulation of calcium-mediated signaling positive regulation of calcium-mediated signaling positive regulation of intracellular signal transduction calcium-mediated signaling cellular component organization extracellular matrix organization cellular component organization or biogenesis extracellular structure organization external encapsulating structure organization positive regulation of phosphorylation regulation of protein modification process regulation of protein phosphorylation positive regulation of protein metabolic process regulation of peptidyl-serine phosphorylation positive regulation of phosphate metabolic process peptidyl-serine modification regulation of primary metabolic process positive regulation of metabolic process positive regulation of protein modification process peptidyl-serine phosphorylation regulation of phosphate metabolic process phosphate-containing compound metabolic process peptidyl-amino acid modification positive regulation of macromolecule metabolic process protein metabolic process positive regulation of protein phosphorylation phosphorus metabolic process protein modification process protein phosphorylation positive regulation of phosphorus metabolic process phosphorylation regulation of protein metabolic process primary metabolic process regulation of macromolecule metabolic process positive regulation of peptidyl-serine phosphorylation macromolecule modification regulation of phosphorus metabolic process metabolic process regulation of phosphorylation macromolecule metabolic process regulation of metabolic process regulation of multicellular organism growth developmental process regulation of growth regulation of developmental growth regulation of developmental process developmental growth growth multicellular organism growth axonogenesis cellular developmental process cell projection organization plasma membrane bounded cell projection morphogenesis cell development neuron projection development cell morphogenesis neurogenesis multicellular organism development cell projection morphogenesis neuron differentiation neuron projection morphogenesis cell differentiation anatomical structure development system development plasma membrane bounded cell projection organization nervous system development axon development cell morphogenesis involved in neuron differentiation generation of neurons anatomical structure morphogenesis neuron development cell growth collateral sprouting in absence of injury collateral sprouting developmental cell growth developmental growth involved in morphogenesis positive regulation of macromolecule biosynthetic process positive regulation of biosynthetic process regulation of cytokine production cytokine production regulation of biosynthetic process gene expression macromolecule biosynthetic process regulation of chemokine production regulation of gene expression biosynthetic process positive regulation of gene expression chemokine production positive regulation of chemokine production positive regulation of multicellular organismal process regulation of macromolecule biosynthetic process positive regulation of cytokine production behavior suckling behavior feeding behavior astrocyte differentiation astrocyte activation glial cell development astrocyte development gliogenesis response to stress defense response cell activation central nervous system development glial cell differentiation glial cell activation inflammatory response neuroinflammatory response Notch signaling pathway cell cycle G2/M phase transition mitotic cell cycle process G2/M transition of mitotic cell cycle cell cycle phase transition cell cycle mitotic cell cycle cell cycle process mitotic cell cycle phase transition myeloid leukocyte activation leukocyte activation macrophage activation immune system process leukocyte activation involved in inflammatory response microglial cell activation cellular homeostasis neuron cellular homeostasis homeostatic process neuron recognition axon choice point recognition cell recognition axon midline choice point recognition axon guidance neuron projection guidance ribonucleotide catabolic process pyridine nucleotide catabolic process oxoacid metabolic process carbohydrate catabolic process carbohydrate derivative metabolic process organophosphate catabolic process regulation of generation of precursor metabolites and energy nucleoside phosphate catabolic process organic acid metabolic process regulation of ATP metabolic process nucleobase-containing compound metabolic process regulation of purine nucleotide catabolic process positive regulation of nucleotide catabolic process regulation of small molecule metabolic process glycolytic process regulation of nucleotide metabolic process pyridine-containing compound metabolic process small molecule metabolic process regulation of nucleobase-containing compound metabolic process purine ribonucleotide catabolic process pyridine nucleotide metabolic process nucleoside phosphate metabolic process nicotinamide nucleotide metabolic process pyruvate metabolic process regulation of carbohydrate catabolic process positive regulation of nucleobase-containing compound metabolic process purine nucleoside diphosphate metabolic process purine-containing compound catabolic process nucleotide metabolic process regulation of purine nucleotide metabolic process nucleobase-containing compound catabolic process positive regulation of ATP metabolic process nucleoside diphosphate metabolic process purine nucleoside diphosphate catabolic process nucleoside diphosphate catabolic process regulation of nucleotide catabolic process positive regulation of carbohydrate metabolic process nucleoside triphosphate metabolic process monocarboxylic acid metabolic process purine ribonucleotide metabolic process pyridine-containing compound catabolic process ribose phosphate metabolic process ATP metabolic process catabolic process positive regulation of nucleotide metabolic process positive regulation of purine nucleotide catabolic process purine nucleotide metabolic process ribonucleotide metabolic process nucleobase-containing small molecule metabolic process purine ribonucleoside triphosphate metabolic process ribonucleoside diphosphate metabolic process ribonucleoside diphosphate catabolic process regulation of carbohydrate metabolic process ribonucleoside triphosphate metabolic process nucleotide catabolic process purine nucleoside triphosphate metabolic process carbohydrate metabolic process purine nucleotide catabolic process carbohydrate derivative catabolic process positive regulation of glycolytic process ADP catabolic process carboxylic acid metabolic process generation of precursor metabolites and energy regulation of catabolic process regulation of glycolytic process purine-containing compound metabolic process positive regulation of purine nucleotide metabolic process positive regulation of catabolic process ADP metabolic process organophosphate metabolic process purine ribonucleoside diphosphate metabolic process positive regulation of small molecule metabolic process purine ribonucleoside diphosphate catabolic process myeloid leukocyte differentiation mononuclear cell differentiation microglia differentiation hemopoiesis macrophage differentiation microglia development myeloid cell differentiation myeloid cell development leukocyte differentiation regulation of cellular component organization positive regulation of cellular component organization positive regulation of amyloid fibril formation regulation of amyloid fibril formation amyloid fibril formation positive regulation of supramolecular fiber organization regulation of supramolecular fiber organization supramolecular fiber organization positive regulation of ERK1 and ERK2 cascade positive regulation of MAPK cascade regulation of MAPK cascade MAPK cascade ERK1 and ERK2 cascade regulation of ERK1 and ERK2 cascade positive regulation of long-term synaptic potentiation regulation of peptidyl-threonine phosphorylation peptidyl-threonine modification positive regulation of peptidyl-threonine phosphorylation peptidyl-threonine phosphorylation cellular localization transport intracellular transport establishment of localization localization axo-dendritic transport establishment of localization in cell microtubule-based transport transport along microtubule cytoskeleton-dependent intracellular transport microtubule-based movement microtubule-based process neuromuscular process neuromuscular process controlling balance secondary alcohol metabolic process sterol metabolic process steroid metabolic process cholesterol metabolic process alcohol metabolic process lipid metabolic process cell junction organization synapse organization head development forebrain development animal organ development brain development regulation of Wnt signaling pathway Wnt signaling pathway neuron apoptotic process apoptotic process cell death programmed cell death ligand-gated ion channel signaling pathway ionotropic glutamate receptor signaling pathway glutamate receptor signaling pathway regulation of non-canonical NF-kappaB signal transduction non-canonical NF-kappaB signal transduction positive regulation of non-canonical NF-kappaB signal transduction regulation of presynapse assembly cellular component biogenesis regulation of nervous system development cellular component assembly regulation of presynapse organization negative regulation of cell junction assembly cell junction assembly negative regulation of cellular process negative regulation of nervous system development regulation of synapse assembly regulation of multicellular organismal development negative regulation of cellular component organization negative regulation of developmental process presynapse organization negative regulation of synapse organization regulation of cellular component biogenesis regulation of cell junction assembly regulation of synapse organization negative regulation of presynapse assembly synapse assembly negative regulation of multicellular organismal process negative regulation of synapse assembly presynapse assembly cell activation involved in immune response astrocyte activation involved in immune response immune response immune effector process negative regulation of metabolic process negative regulation of gene expression negative regulation of biosynthetic process negative regulation of macromolecule biosynthetic process negative regulation of macromolecule metabolic process positive regulation of cell cycle regulation of mitotic cell cycle positive regulation of mitotic cell cycle regulation of cell cycle regulation of tumor necrosis factor production positive regulation of tumor necrosis factor superfamily cytokine production tumor necrosis factor superfamily cytokine production positive regulation of tumor necrosis factor production tumor necrosis factor production regulation of tumor necrosis factor superfamily cytokine production response to oxidative stress neuron projection maintenance neuron projection organization 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 cellular response to chemical stimulus response to chemical response to amyloid-beta regulation of cell cycle phase transition positive regulation of mitotic cell cycle phase transition positive regulation of cell cycle process positive regulation of G2/M transition of mitotic cell cycle regulation of G2/M transition of mitotic cell cycle regulation of cell cycle process regulation of cell cycle G2/M phase transition positive regulation of cell cycle G2/M phase transition regulation of mitotic cell cycle phase transition positive regulation of cell cycle phase transition regulation of cell differentiation negative regulation of cell differentiation negative regulation of neuron differentiation regulation of neuron differentiation learning learning or memory cognition regulation of defense response regulation of response to external stimulus response to external stimulus regulation of inflammatory response positive regulation of response to external stimulus positive regulation of inflammatory response regulation of response to stress positive regulation of defense response inorganic ion homeostasis intracellular copper ion homeostasis copper ion homeostasis chemical homeostasis intracellular monoatomic cation homeostasis monoatomic ion homeostasis intracellular chemical homeostasis monoatomic cation homeostasis intracellular monoatomic ion homeostasis developmental maturation neuron remodeling anatomical structure maturation neuron maturation cell maturation reproductive process multicellular organismal reproductive process reproductive behavior mating behavior peptidyl-tyrosine modification regulation of peptidyl-tyrosine phosphorylation peptidyl-tyrosine phosphorylation translation post-transcriptional regulation of gene expression regulation of translation interleukin-1 production regulation of interleukin-1 beta production positive regulation of interleukin-1 beta production positive regulation of interleukin-1 production regulation of interleukin-1 production interleukin-1 beta production regulation of neuronal synaptic plasticity regulation of long-term neuronal synaptic plasticity positive regulation of JNK cascade JNK cascade regulation of JNK cascade positive regulation of locomotion regulation of cell motility regulation of lymphocyte migration positive regulation of cell migration positive regulation of cell motility regulation of cell migration positive regulation of mononuclear cell migration cell migration regulation of immune system process cell motility regulation of mononuclear cell migration positive regulation of immune system process locomotion positive regulation of lymphocyte migration regulation of leukocyte migration positive regulation of T cell migration lymphocyte migration positive regulation of leukocyte migration leukocyte migration regulation of locomotion regulation of T cell migration mononuclear cell migration T cell migration cell adhesion NMDA selective glutamate receptor signaling pathway positive regulation of DNA-templated transcription RNA metabolic process RNA biosynthetic process nucleic acid biosynthetic process DNA-templated transcription regulation of RNA metabolic process transcription by RNA polymerase II regulation of RNA biosynthetic process regulation of transcription by RNA polymerase II positive regulation of transcription by RNA polymerase II nucleobase-containing compound biosynthetic process nucleic acid metabolic process positive regulation of RNA metabolic process positive regulation of RNA biosynthetic process regulation of DNA-templated transcription locomotory behavior adult locomotory behavior adult behavior cytosolic mRNA polyadenylation mRNA metabolic process interleukin-6 production positive regulation of interleukin-6 production regulation of interleukin-6 production import into cell endocytosis vesicle-mediated transport spontaneous synaptic transmission regulation of spontaneous synaptic transmission response to peptide response to cytokine response to interleukin-1 neuromuscular junction development synaptic assembly at neuromuscular junction response to light stimulus visual learning visual behavior associative learning response to radiation response to abiotic stimulus dendrite development negative regulation of cell population proliferation cell population proliferation regulation of cell population proliferation intracellular calcium ion homeostasis smooth endoplasmic reticulum calcium ion homeostasis calcium ion homeostasis endoplasmic reticulum calcium ion homeostasis	somatodendritic compartment cell body cellular anatomical structure perikaryon neuronal cell body presynapse synapse cell junction presynaptic active zone cell-cell junction anchoring junction intracellular anatomical structure cytoplasm cytosol somatodendritic compartment cell body cellular anatomical structure perikaryon neuronal cell body presynapse synapse cell junction presynaptic active zone cell-cell junction anchoring junction intracellular anatomical structure cytoplasm cytosol membrane-bounded organelle intracellular organelle organelle endoplasmic reticulum smooth endoplasmic reticulum intracellular membrane-bounded organelle endomembrane system protein-containing complex receptor complex neuromuscular junction membrane-enclosed lumen intracellular organelle lumen endoplasmic reticulum lumen organelle lumen endosome intracellular vesicle recycling endosome cytoplasmic vesicle vesicle neuron spine neuron projection dendritic spine plasma membrane bounded cell projection cell projection postsynapse dendrite dendritic tree ciliary rootlet intracellular membraneless organelle cilium cytoskeleton membraneless organelle extracellular region extracellular space transport vesicle synaptic vesicle secretory vesicle exocytic vesicle mitochondrial membrane organelle inner membrane mitochondrion membrane mitochondrial inner membrane organelle envelope mitochondrial envelope organelle membrane cell surface cell periphery plasma membrane membrane microdomain membrane raft Golgi apparatus subcompartment Golgi apparatus organelle subcompartment trans-Golgi network membrane trans-Golgi network clathrin-coated pit apical part of cell spindle spindle midzone microtubule cytoskeleton extracellular exosome extracellular vesicle extracellular organelle extracellular membrane-bounded organelle COPII-coated ER to Golgi transport vesicle coated vesicle nucleus organelle envelope lumen nuclear envelope lumen nuclear envelope dendritic shaft perinuclear region of cytoplasm vesicle lumen cytoplasmic vesicle lumen secretory granule lumen secretory granule platelet alpha granule platelet alpha granule lumen axon Golgi-associated vesicle growth cone distal axon site of polarized growth early endosome Golgi lumen endosome lumen

InterPro: Protein Family Classification InterPro Database Homepage

Chains	Accession	Name	Type
C [auth A]	IPR013803	Amyloidogenic glycoprotein, amyloid-beta peptide	Domain
C [auth A]	IPR008154	Amyloidogenic glycoprotein, extracellular	Domain
C [auth A]	IPR036176	E2 domain superfamily	Homologous Superfamily
C [auth A]	IPR024329	Amyloidogenic glycoprotein, E2 domain	Domain
C [auth A]	IPR036669	Amyloidogenic glycoprotein, copper-binding domain superfamily	Homologous Superfamily
C [auth A]	IPR019745	Amyloidogenic glycoprotein, intracellular domain, conserved site	Conserved Site
C [auth A]	IPR011178	Amyloidogenic glycoprotein, copper-binding	Domain
C [auth A]	IPR037071	Amyloidogenic glycoprotein, amyloid-beta peptide superfamily	Homologous Superfamily
C [auth A]	IPR020901	Proteinase inhibitor I2, Kunitz, conserved site	Conserved Site
C [auth A]	IPR019744	Amyloidogenic glycoprotein, copper-binding domain conserved site	Conserved Site
C [auth A]	IPR002223	Pancreatic trypsin inhibitor Kunitz domain	Domain
C [auth A]	IPR015849	Amyloidogenic glycoprotein, heparin-binding	Domain
C [auth A]	IPR036454	Amyloidogenic glycoprotein, heparin-binding domain superfamily	Homologous Superfamily
C [auth A]	IPR011993	PH-like domain superfamily	Homologous Superfamily
C [auth A]	IPR019543	Beta-amyloid precursor protein C-terminal	Domain
C [auth A]	IPR036880	Pancreatic trypsin inhibitor Kunitz domain superfamily	Homologous Superfamily
C [auth A]	IPR008155	Amyloidogenic glycoprotein	Family

Pharos: Disease Associations Pharos Homepage Annotation

Chains	Drug Target	Associated Disease
C [auth A]	Pharos: P05067	Alzheimer disease amyloidosis cerebral amyloid angiopathy dementia cerebral amyloid angiopathy, APP-related fragile X syndrome Down syndrome neurodegenerative disease Necrosis brain disease premature aging syndrome Alzheimer disease type 1 spinal cord disease dissociative amnesia endogenous depression Alzheimer disease amyloidosis cerebral amyloid angiopathy dementia cerebral amyloid angiopathy, APP-related fragile X syndrome Down syndrome neurodegenerative disease Necrosis brain disease premature aging syndrome Alzheimer disease type 1 spinal cord disease dissociative amnesia endogenous depression amnestic disorder Gerstmann-Straussler-Scheinker syndrome osteosarcoma astrocytic tumor Huntington disease juvenile dermatomyositis ABeta amyloidosis, Arctic type Pick disease learning disability ABeta amyloidosis, Italian type cerebrovascular disorder Lewy body dementia prion disease malignant ependymoma amyotrophic lateral sclerosis ovarian cancer atypical teratoid rhabdoid tumor Parkinson disease breast cancer large cell medulloblastoma ABeta amyloidosis, dutch type ABetaL34V amyloidosis chronic obstructive pulmonary disease ACys amyloidosis psoriasis medulloblastoma depressive disorder Emery-Dreifuss muscular dystrophy FRAXE intellectual disability oligodendroglioma anxiety disorder head and neck cancer palsy bipolar disorder periodic fever syndrome cardiomyopathy ABeta amyloidosis, Iowa type polycystic ovary syndrome acquired metabolic disease lung carcinoma ADan amyloidosis rheumatoid arthritis dermatomyositis toxic encephalopathy

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.