9IWJ | pdb_00009iwj

X-ray structure of human PPARalpha ligand binding domain-NCoR2 corepressor peptide co-crystals obtained by co-crystallization

External Resource: Annotation

Gene Ontology: Gene Product Annotation
InterPro: Protein Family Classification
Pharos: Disease Associations

Gene Ontology: Gene Product Annotation Gene Ontology Database Homepage

Chains	Polymer	Molecular Function	Biological Process	Cellular Component
A, B, C, D	Peroxisome proliferator-activated receptor alpha	sequence-specific DNA binding DNA binding binding nucleic acid binding DNA-binding transcription factor activity, RNA polymerase II-specific transcription regulator activity DNA-binding transcription factor activity protein-containing complex binding nuclear receptor activity molecular transducer activity signaling receptor activity ligand-modulated transcription factor activity phosphatase binding protein binding sequence-specific DNA binding DNA binding binding nucleic acid binding DNA-binding transcription factor activity, RNA polymerase II-specific transcription regulator activity DNA-binding transcription factor activity protein-containing complex binding nuclear receptor activity molecular transducer activity signaling receptor activity ligand-modulated transcription factor activity phosphatase binding protein binding enzyme binding kinase binding mitogen-activated protein kinase kinase kinase binding protein kinase binding DNA-binding transcription activator activity, RNA polymerase II-specific DNA-binding transcription activator activity protein domain specific binding DNA-binding transcription repressor activity, RNA polymerase II-specific DNA-binding transcription repressor activity transcription factor binding RNA polymerase II-specific DNA-binding transcription factor binding DNA-binding transcription factor 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 NFAT protein binding MDM2/MDM4 family protein binding nuclear steroid receptor activity ubiquitin-like protein conjugating enzyme binding ubiquitin conjugating enzyme binding transcription coregulator binding transcription coactivator binding lipid binding cation binding transition metal ion binding zinc ion binding ion binding metal ion binding small molecule binding	regulation of biological process regulation of cellular process ketone metabolic process biological regulation metabolic process cellular process regulation of metabolic process regulation of ketone metabolic process developmental process heart development multicellular organism development multicellular organismal process anatomical structure development animal organ development regulation of biological process regulation of cellular process ketone metabolic process biological regulation metabolic process cellular process regulation of metabolic process regulation of ketone metabolic process developmental process heart development multicellular organism development multicellular organismal process anatomical structure development animal organ development circulatory system development system development oxoacid metabolic process regulation of lipid metabolic process positive regulation of biological process organic acid metabolic process regulation of primary metabolic process regulation of fatty acid oxidation positive regulation of metabolic process fatty acid oxidation regulation of small molecule metabolic process positive regulation of lipid metabolic process small molecule metabolic process lipid oxidation positive regulation of cellular process positive regulation of fatty acid metabolic process fatty acid metabolic process carboxylic acid metabolic process lipid modification primary metabolic process positive regulation of fatty acid oxidation regulation of fatty acid metabolic process monocarboxylic acid metabolic process positive regulation of small molecule metabolic process lipid metabolic process catabolic process organic acid catabolic process positive regulation of fatty acid beta-oxidation monocarboxylic acid catabolic process positive regulation of lipid catabolic process carboxylic acid catabolic process fatty acid beta-oxidation lipid catabolic process regulation of fatty acid beta-oxidation regulation of catabolic process regulation of lipid catabolic process fatty acid catabolic process positive regulation of catabolic process small molecule catabolic process symbiont-mediated perturbation of host cellular process biological process involved in interspecies interaction between organisms symbiont-mediated transformation of host cell biological process involved in interaction with host biological process involved in symbiotic interaction positive regulation of transformation of host cell by virus regulation of transformation of host cell by virus symbiont-mediated perturbation of host process modulation of process of another organism regulation of biological process involved in symbiotic interaction regulation of cell adhesion negative regulation of biological process leukocyte cell-cell adhesion negative regulation of cell adhesion cell adhesion cell-cell adhesion negative regulation of leukocyte cell-cell adhesion negative regulation of cell-cell adhesion regulation of leukocyte cell-cell adhesion negative regulation of cellular process regulation of cell-cell adhesion ribonucleotide catabolic process pyridine nucleotide catabolic process negative regulation of small molecule metabolic process negative regulation of glycolytic process carbohydrate catabolic process organophosphate catabolic process carbohydrate derivative metabolic process regulation of generation of precursor metabolites and energy nucleoside phosphate catabolic process negative regulation of ATP metabolic process regulation of ATP metabolic process nucleobase-containing compound metabolic process regulation of purine nucleotide catabolic process negative regulation of nucleotide metabolic process glycolytic process regulation of nucleotide metabolic process regulation of phosphate metabolic process phosphate-containing compound metabolic process pyridine-containing compound metabolic process negative regulation of nucleobase-containing compound metabolic process regulation of nucleobase-containing compound metabolic process purine ribonucleotide catabolic process phosphorus metabolic process pyridine nucleotide metabolic process negative regulation of carbohydrate metabolic process nucleoside phosphate metabolic process nicotinamide nucleotide metabolic process pyruvate metabolic process regulation of carbohydrate catabolic process negative regulation of metabolic process negative regulation of purine nucleotide catabolic 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 nucleoside diphosphate metabolic process purine nucleoside diphosphate catabolic process nucleoside diphosphate catabolic process regulation of nucleotide catabolic process regulation of phosphorus metabolic process nucleoside triphosphate metabolic process purine ribonucleotide metabolic process pyridine-containing compound catabolic process ribose phosphate metabolic process ATP metabolic process negative regulation of purine nucleotide metabolic process negative regulation of phosphate metabolic 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 nucleotide catabolic process ribonucleoside triphosphate metabolic process negative regulation of nucleotide catabolic process negative regulation of catabolic process purine nucleoside triphosphate metabolic process purine nucleotide catabolic process carbohydrate metabolic process carbohydrate derivative catabolic process ADP catabolic process generation of precursor metabolites and energy regulation of glycolytic process purine-containing compound metabolic process ADP metabolic process organophosphate metabolic process negative regulation of phosphorus metabolic process purine ribonucleoside diphosphate metabolic process purine ribonucleoside diphosphate catabolic process negative regulation of hepatocyte apoptotic process regulation of epithelial cell apoptotic process negative regulation of programmed cell death regulation of apoptotic process regulation of programmed cell death cell death epithelial cell apoptotic process negative regulation of apoptotic process regulation of hepatocyte apoptotic process negative regulation of epithelial cell apoptotic process hepatocyte apoptotic process apoptotic process programmed cell death regulation of biosynthetic process rhythmic process circadian regulation of gene expression circadian rhythm regulation of macromolecule metabolic process gene expression macromolecule biosynthetic process regulation of gene expression biosynthetic process regulation of macromolecule biosynthetic process macromolecule metabolic process cellular response to stimulus cellular response to nutrient levels response to nutrient levels response to stimulus cellular response to stress response to stress response to starvation cellular response to starvation negative regulation of transforming growth factor beta receptor signaling pathway cell surface receptor protein serine/threonine kinase signaling pathway cellular response to growth factor stimulus negative regulation of signaling signaling cellular response to transforming growth factor beta stimulus regulation of transmembrane receptor protein serine/threonine kinase signaling pathway regulation of signal transduction negative regulation of cell communication cell communication regulation of transforming growth factor beta receptor signaling pathway cellular response to endogenous stimulus signal transduction enzyme-linked receptor protein signaling pathway regulation of signaling cell surface receptor signaling pathway negative regulation of response to stimulus regulation of cellular response to transforming growth factor beta stimulus response to endogenous stimulus regulation of cellular response to growth factor stimulus negative regulation of signal transduction response to transforming growth factor beta regulation of response to stimulus transforming growth factor beta receptor signaling pathway regulation of cell communication response to growth factor transforming growth factor beta receptor superfamily signaling pathway negative regulation of transmembrane receptor protein serine/threonine kinase signaling pathway regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction negative regulation of intracellular signal transduction negative regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction intracellular signal transduction regulation of intracellular signal transduction intracellular signaling cassette phosphatidylinositol 3-kinase/protein kinase B signal transduction intracellular receptor signaling pathway peroxisome proliferator activated receptor signaling pathway nuclear receptor-mediated signaling pathway monosaccharide metabolic process small molecule biosynthetic process carbohydrate biosynthetic process hexose metabolic process monosaccharide biosynthetic process gluconeogenesis hexose biosynthetic process glucose metabolic process response to decreased oxygen levels response to hypoxia response to oxygen levels response to abiotic stimulus nucleotide biosynthetic process purine ribonucleotide biosynthetic process positive regulation of phosphate metabolic process purine ribonucleoside triphosphate biosynthetic process positive regulation of nucleotide biosynthetic process regulation of nucleotide biosynthetic process ribonucleotide biosynthetic process purine nucleoside triphosphate biosynthetic process positive regulation of purine nucleotide biosynthetic process ribose phosphate biosynthetic process positive regulation of nucleobase-containing compound metabolic process positive regulation of phosphorus metabolic process ribonucleoside triphosphate biosynthetic process positive regulation of ATP metabolic process organophosphate biosynthetic process nucleoside phosphate biosynthetic process purine nucleotide biosynthetic process ATP biosynthetic process positive regulation of nucleotide metabolic process positive regulation of biosynthetic process purine-containing compound biosynthetic process carbohydrate derivative biosynthetic process regulation of purine nucleotide biosynthetic process nucleoside triphosphate biosynthetic process nucleobase-containing compound biosynthetic process positive regulation of purine nucleotide metabolic process positive regulation of ATP biosynthetic process regulation of ATP biosynthetic process RNA metabolic process negative regulation of RNA biosynthetic process RNA biosynthetic process DNA-templated transcription nucleic acid biosynthetic process regulation of RNA metabolic process transcription by RNA polymerase II regulation of RNA biosynthetic process negative regulation of macromolecule metabolic process regulation of transcription by RNA polymerase II negative regulation of DNA-templated transcription negative regulation of transcription by RNA polymerase II nucleic acid metabolic process negative regulation of biosynthetic process negative regulation of macromolecule biosynthetic process regulation of DNA-templated transcription negative regulation of RNA metabolic process positive regulation of DNA-templated transcription positive regulation of macromolecule biosynthetic process positive regulation of macromolecule metabolic process positive regulation of transcription by RNA polymerase II positive regulation of RNA metabolic process positive regulation of RNA biosynthetic process regulation of glucose metabolic process positive regulation of gluconeogenesis positive regulation of glucose metabolic process regulation of gluconeogenesis positive regulation of carbohydrate metabolic process regulation of carbohydrate biosynthetic process regulation of developmental process cellular developmental process negative regulation of developmental process macrophage derived foam cell differentiation regulation of cell differentiation negative regulation of macrophage derived foam cell differentiation foam cell differentiation cell differentiation regulation of macrophage derived foam cell differentiation negative regulation of cell differentiation regulation of response to nutrient levels negative regulation of response to food negative regulation of response to nutrient levels negative regulation of appetite regulation of response to food response to food response to chemical regulation of biological quality regulation of appetite system process regulation of growth negative regulation of muscle hypertrophy regulation of cardiac muscle tissue growth developmental growth regulation of system process negative regulation of muscle cell differentiation muscle cell differentiation regulation of muscle hypertrophy muscle structure development muscle adaptation negative regulation of growth regulation of organ growth regulation of heart growth cardiac muscle tissue growth muscle tissue development cardiac cell development heart growth negative regulation of striated muscle cell differentiation striated muscle hypertrophy negative regulation of cell growth tissue development negative regulation of developmental growth regulation of muscle cell differentiation striated muscle cell differentiation negative regulation of multicellular organismal process regulation of cellular component organization cardiac muscle cell development cell development negative regulation of cell growth involved in cardiac muscle cell development regulation of striated muscle cell differentiation negative regulation of cardiac muscle tissue growth organ growth cell growth striated muscle tissue development cellular component organization negative regulation of organ growth striated muscle cell development muscle cell development cardiac muscle hypertrophy regulation of multicellular organismal process cellular component organization or biogenesis muscle hypertrophy regulation of muscle adaptation regulation of multicellular organismal development regulation of developmental growth negative regulation of heart growth cardiac muscle tissue development developmental cell growth physiological muscle hypertrophy growth cardiac muscle cell differentiation regulation of cell growth involved in cardiac muscle cell development regulation of muscle system process muscle system process regulation of cell growth regulation of cardiac muscle hypertrophy cardiocyte differentiation cell growth involved in cardiac muscle cell development physiological cardiac muscle hypertrophy negative regulation of cardiac muscle hypertrophy nitric oxide metabolic process reactive nitrogen species metabolic process enamel mineralization tooth mineralization odontogenesis of dentin-containing tooth odontogenesis amelogenesis anatomical structure morphogenesis anatomical structure formation involved in morphogenesis animal organ morphogenesis biomineral tissue development regulation of circadian rhythm cholesterol storage regulation of localization negative regulation of cholesterol storage lipid storage lipid localization negative regulation of lipid localization localization regulation of lipid storage regulation of lipid localization negative regulation of lipid storage macromolecule localization nutrient storage regulation of cholesterol storage hormone-mediated signaling pathway cellular response to chemical stimulus response to hormone cellular response to hormone stimulus reactive oxygen species biosynthetic process reactive oxygen species metabolic process regulation of reactive oxygen species biosynthetic process negative regulation of reactive oxygen species metabolic process negative regulation of reactive oxygen species biosynthetic process regulation of reactive oxygen species metabolic process regulation of defense response regulation of response to external stimulus negative regulation of inflammatory response defense response response to external stimulus regulation of inflammatory response negative regulation of response to external stimulus regulation of response to stress negative regulation of defense response inflammatory response epidermis development lipid biosynthetic process positive regulation of lipid biosynthetic process regulation of lipid biosynthetic process response to alcohol response to oxygen-containing compound response to ethanol negative regulation of miRNA transcription miRNA transcription regulation of miRNA metabolic process miRNA metabolic process negative regulation of miRNA metabolic process regulation of miRNA transcription response to peptide hormone response to insulin response to nitrogen compound wound healing response to wounding lipoprotein metabolic process protein metabolic process cellular response to fructose stimulus cellular response to oxygen-containing compound response to hexose cellular response to carbohydrate stimulus response to monosaccharide response to carbohydrate cellular response to hexose stimulus cellular response to monosaccharide stimulus response to fructose organic anion transport carboxylic acid transport regulation of transport transport lipid transport regulation of lipid transport regulation of fatty acid transport establishment of localization organic acid transport monocarboxylic acid transport fatty acid transport regulation of organic acid transport behavior adult behavior response to nicotine behavioral response to nicotine response to nutrient circulatory system process regulation of blood pressure negative regulation of blood pressure blood circulation regulation of cytokine production involved in inflammatory response cytokine production regulation of cytokine production negative regulation of cytokine production involved in inflammatory response production of molecular mediator involved in inflammatory response negative regulation of cytokine production cytokine production involved in inflammatory response negative regulation of gene expression	intracellular organelle cellular anatomical structure intracellular anatomical structure organelle membraneless organelle intracellular membraneless organelle chromatin chromosome membrane-bounded organelle nucleus membrane-enclosed lumen intracellular membrane-bounded organelle intracellular organelle lumen nucleoplasm intracellular organelle cellular anatomical structure intracellular anatomical structure organelle membraneless organelle intracellular membraneless organelle chromatin chromosome membrane-bounded organelle nucleus membrane-enclosed lumen intracellular membrane-bounded organelle intracellular organelle lumen nucleoplasm organelle lumen nuclear lumen
E, F, G, H	Nuclear receptor corepressor 2	transcription factor binding RNA polymerase II-specific DNA-binding transcription factor binding nuclear receptor binding protein binding binding nuclear glucocorticoid receptor binding DNA-binding transcription factor binding signaling receptor binding Notch binding histone deacetylase binding enzyme binding chromatin binding DNA binding nucleic acid binding transcription factor binding RNA polymerase II-specific DNA-binding transcription factor binding nuclear receptor binding protein binding binding nuclear glucocorticoid receptor binding DNA-binding transcription factor binding signaling receptor binding Notch binding histone deacetylase binding enzyme binding chromatin binding DNA binding nucleic acid binding transcription corepressor activity transcription regulator activity transcription coregulator activity protein-macromolecule adaptor activity molecular adaptor activity enzyme regulator activity enzyme activator activity molecular function activator activity molecular function regulator activity catalytic activity protein-containing complex binding nuclear retinoic acid receptor binding nuclear retinoid X receptor binding	regulation of cellular process negative regulation of biological process RNA metabolic process regulation of primary metabolic process negative regulation of RNA biosynthetic process RNA biosynthetic process nucleobase-containing compound metabolic process DNA-templated transcription nucleic acid biosynthetic process regulation of RNA metabolic process negative regulation of cellular process negative regulation of nucleobase-containing compound metabolic process regulation of nucleobase-containing compound metabolic process regulation of RNA biosynthetic process regulation of cellular process negative regulation of biological process RNA metabolic process regulation of primary metabolic process negative regulation of RNA biosynthetic process RNA biosynthetic process nucleobase-containing compound metabolic process DNA-templated transcription nucleic acid biosynthetic process regulation of RNA metabolic process negative regulation of cellular process negative regulation of nucleobase-containing compound metabolic process regulation of nucleobase-containing compound metabolic process regulation of RNA biosynthetic process negative regulation of macromolecule metabolic process regulation of biosynthetic process negative regulation of DNA-templated transcription regulation of biological process negative regulation of metabolic process biological regulation primary metabolic process regulation of macromolecule metabolic process nucleobase-containing compound biosynthetic process gene expression macromolecule biosynthetic process nucleic acid metabolic process regulation of gene expression biosynthetic process negative regulation of biosynthetic process negative regulation of macromolecule biosynthetic process metabolic process cellular process regulation of macromolecule biosynthetic process macromolecule metabolic process regulation of DNA-templated transcription regulation of metabolic process negative regulation of RNA metabolic process ketone metabolic process regulation of ketone metabolic process ovulation cycle rhythmic process estrous cycle reproductive process multicellular organismal reproductive process developmental process multicellular organismal process head development animal organ development brain development nervous system development multicellular organism development cerebellum development central nervous system development metencephalon development anatomical structure development hindbrain development system development negative regulation of miRNA transcription miRNA transcription regulation of miRNA metabolic process miRNA metabolic process negative regulation of miRNA metabolic process regulation of miRNA transcription regulation of body fluid levels secretion transport mammary gland development gland development establishment of localization body fluid secretion localization lactation regulation of biological quality cellular response to stimulus intracellular receptor signaling pathway response to stimulus response to lipid signaling negative regulation of signaling negative regulation of intracellular signal transduction regulation of signal transduction hormone-mediated signaling pathway intracellular signal transduction negative regulation of cell communication cell communication negative regulation of intracellular steroid hormone receptor signaling pathway cellular response to endogenous stimulus response to hormone regulation of intracellular signal transduction response to steroid hormone regulation of intracellular steroid hormone receptor signaling pathway signal transduction androgen receptor signaling pathway nuclear receptor-mediated steroid hormone signaling pathway cellular response to steroid hormone stimulus steroid hormone receptor signaling pathway cellular response to hormone stimulus regulation of signaling negative regulation of response to stimulus response to endogenous stimulus negative regulation of signal transduction regulation of androgen receptor signaling pathway cellular response to chemical stimulus regulation of response to stimulus response to chemical cellular response to lipid negative regulation of androgen receptor signaling pathway regulation of cell communication nuclear receptor-mediated signaling pathway transcription by RNA polymerase II regulation of transcription by RNA polymerase II negative regulation of transcription by RNA polymerase II response to estradiol response to oxygen-containing compound	membrane-bounded organelle intracellular anatomical structure nucleus membrane-enclosed lumen intracellular membrane-bounded organelle intracellular organelle lumen intracellular organelle cellular anatomical structure organelle lumen organelle nuclear lumen nuclear matrix membrane nucleoplasm membrane-bounded organelle intracellular anatomical structure nucleus membrane-enclosed lumen intracellular membrane-bounded organelle intracellular organelle lumen intracellular organelle cellular anatomical structure organelle lumen organelle nuclear lumen nuclear matrix membrane nucleoplasm membraneless organelle intracellular membraneless organelle chromatin chromosome protein-containing complex transcription regulator complex transcription repressor complex nuclear body

InterPro: Protein Family Classification InterPro Database Homepage

Chains	Accession	Name	Type
A, B, C, D	IPR001628	Zinc finger, nuclear hormone receptor-type	Domain
A, B, C, D	IPR003076	Peroxisome proliferator-activated receptor alpha	Family
A, B, C, D	IPR013088	Zinc finger, NHR/GATA-type	Homologous Superfamily
A, B, C, D	IPR003074	Peroxisome proliferator-activated receptor	Family
A, B, C, D	IPR050234	Nuclear hormone receptor family NR1 subfamily	Family
A, B, C, D	IPR001723	Nuclear hormone receptor	Family
A, B, C, D	IPR000536	Nuclear hormone receptor, ligand-binding domain	Domain
A, B, C, D	IPR035500	Nuclear hormone receptor-like domain superfamily	Homologous Superfamily
E, F, G, H	IPR017930	Myb domain	Domain
E, F, G, H	IPR051571	Nuclear receptor corepressor	Family
E, F, G, H	IPR009057	Homedomain-like superfamily	Homologous Superfamily
E, F, G, H	IPR031557	N-CoR, GPS2-interacting domain	Domain
E, F, G, H	IPR017884	SANT domain	Domain
E, F, G, H	IPR001005	SANT/Myb domain	Domain

Pharos: Disease Associations Pharos Homepage Annotation

Chains	Drug Target	Associated Disease
A, B, C, D	Pharos: Q07869	myopathy hypertriglyceridemia type 2 diabetes mellitus cancer obesity disorder Crohn disease non-alcoholic fatty liver disease hypertensive disorder Hepatomegaly abdominal obesity-metabolic syndrome acute kidney tubular necrosis proteinuria carcinoma chronic kidney disease hypoglycemia myopathy hypertriglyceridemia type 2 diabetes mellitus cancer obesity disorder Crohn disease non-alcoholic fatty liver disease hypertensive disorder Hepatomegaly abdominal obesity-metabolic syndrome acute kidney tubular necrosis proteinuria carcinoma chronic kidney disease hypoglycemia prostate cancer kidney disease liver cancer sarcomatoid carcinoma experimental autoimmune encephalomyelitis familial hyperlipidemia coronary artery disease hyperlipidemia ovarian cancer pancreatic intraductal papillary-mucinous neoplasm with low grade dysplasia ileocolitis inherited lipid metabolism disorder invasive ductal breast carcinoma alcoholic fatty liver disease large cell medulloblastoma ductal breast carcinoma in situ liver disease attention deficit hyperactivity disorder, inattentive type schizophrenia benign neoplasm maturity-onset diabetes of the young muscular disease hyperlipoproteinemia pancreatic ductal adenocarcinoma hypoalphalipoproteinemia Pick disease inborn carbohydrate metabolic disorder primitive neuroectodermal tumor ischemia reperfusion injury drug-induced liver injury atherosclerosis liver neoplasm atypical teratoid rhabdoid tumor mammary neoplasms, animal bipolar disorder undifferentiated carcinoma medulloblastoma hyperglycemia osteosarcoma Crohn's colitis pancreatic intraductal papillary-mucinous neoplasm dermatitis, atopic plantar fibromatosis atopic eczema malignant ependymoma autism spectrum disorder breast carcinoma muscle tissue disease fatty liver disease
E, F, G, H	Pharos: Q9Y618	Liver Cirrhosis, Experimental astrocytic tumor hypertensive disorder mature T-cell and NK-cell non-Hodgkin lymphoma ovarian cancer psoriasis bipolar disorder juvenile dermatomyositis myocardial infarction pancreatic ductal adenocarcinoma heart disease osteoarthritis primary cutaneous T-cell lymphoma

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.