8BDM

VCB in complex with compound 26

External Resource: Annotation

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

Domain Annotation: SCOP2 Classification SCOP2 Database Homepage

Chains	Type	Family Name	Domain Identifier	Family Identifier	Provenance Source (Version)
A [auth G]	SCOP2B Superfamily	Ubiquitin-like	8038575	3000157	SCOP2B (2022-06-29)
D	SCOP2B Superfamily	Ubiquitin-like	8038575	3000157	SCOP2B (2022-06-29)
G [auth A]	SCOP2B Superfamily	Ubiquitin-like	8038575	3000157	SCOP2B (2022-06-29)
J	SCOP2B Superfamily	Ubiquitin-like	8038575	3000157	SCOP2B (2022-06-29)
C [auth I]	SCOP2B Superfamily	VHL	8041313	3000841	SCOP2B (2022-06-29)
F	SCOP2B Superfamily	VHL	8041313	3000841	SCOP2B (2022-06-29)
I [auth C]	SCOP2B Superfamily	VHL	8041313	3000841	SCOP2B (2022-06-29)
L	SCOP2B Superfamily	VHL	8041313	3000841	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 [auth G]	ubiquitin_2	e8bdmG1	A: a+b two layers	X: beta-Grasp	H: Ubiquitin-related	T: Ubiquitin-like	F: ubiquitin_2	ECOD (1.6)
D	ubiquitin_2	e8bdmD1	A: a+b two layers	X: beta-Grasp	H: Ubiquitin-related	T: Ubiquitin-like	F: ubiquitin_2	ECOD (1.6)
G [auth A]	ubiquitin_2	e8bdmA1	A: a+b two layers	X: beta-Grasp	H: Ubiquitin-related	T: Ubiquitin-like	F: ubiquitin_2	ECOD (1.6)
J	ubiquitin_2	e8bdmJ1	A: a+b two layers	X: beta-Grasp	H: Ubiquitin-related	T: Ubiquitin-like	F: ubiquitin_2	ECOD (1.6)
B [auth H]	Skp1_POZ_1	e8bdmH1	A: a+b two layers	X: POZ domain (From Topology)	H: POZ domain (From Topology)	T: POZ domain	F: Skp1_POZ_1	ECOD (1.6)
E	Skp1_POZ_1	e8bdmE1	A: a+b two layers	X: POZ domain (From Topology)	H: POZ domain (From Topology)	T: POZ domain	F: Skp1_POZ_1	ECOD (1.6)
H [auth B]	Skp1_POZ_1	e8bdmB1	A: a+b two layers	X: POZ domain (From Topology)	H: POZ domain (From Topology)	T: POZ domain	F: Skp1_POZ_1	ECOD (1.6)
K	Skp1_POZ_1	e8bdmK1	A: a+b two layers	X: POZ domain (From Topology)	H: POZ domain (From Topology)	T: POZ domain	F: Skp1_POZ_1	ECOD (1.6)
C [auth I]	VHL	e8bdmI1	A: beta sandwiches	X: Immunoglobulin-like beta-sandwich	H: Immunoglobulin-related	T: Prealbumin-like	F: VHL	ECOD (1.6)
C [auth I]	VHL_C	e8bdmI2	A: alpha arrays	X: SOCS box-like (From Topology)	H: SOCS box-like (From Topology)	T: SOCS box-like	F: VHL_C	ECOD (1.6)
F	VHL	e8bdmF2	A: beta sandwiches	X: Immunoglobulin-like beta-sandwich	H: Immunoglobulin-related	T: Prealbumin-like	F: VHL	ECOD (1.6)
F	VHL_C	e8bdmF1	A: alpha arrays	X: SOCS box-like (From Topology)	H: SOCS box-like (From Topology)	T: SOCS box-like	F: VHL_C	ECOD (1.6)
I [auth C]	VHL	e8bdmC2	A: beta sandwiches	X: Immunoglobulin-like beta-sandwich	H: Immunoglobulin-related	T: Prealbumin-like	F: VHL	ECOD (1.6)
I [auth C]	VHL_C	e8bdmC1	A: alpha arrays	X: SOCS box-like (From Topology)	H: SOCS box-like (From Topology)	T: SOCS box-like	F: VHL_C	ECOD (1.6)
L	VHL	e8bdmL1	A: beta sandwiches	X: Immunoglobulin-like beta-sandwich	H: Immunoglobulin-related	T: Prealbumin-like	F: VHL	ECOD (1.6)
L	VHL_C	e8bdmL2	A: alpha arrays	X: SOCS box-like (From Topology)	H: SOCS box-like (From Topology)	T: SOCS box-like	F: VHL_C	ECOD (1.6)

Protein Family Annotation Pfam Database Homepage

Chains	Accession	Name	Description	Comments	Source
A [auth G], D, G [auth A], J	PF00240	Ubiquitin family (ubiquitin)	Ubiquitin family	This family contains a number of ubiquitin-like proteins: SUMO (smt3 homologue) (see Swiss:Q02724), Nedd8 (see Swiss:P29595), Elongin B (see Swiss:Q15370), Rub1 (see Swiss:Q9SHE7), and Parkin (see Swiss:O60260). A number of them are thought to carry ...	This family contains a number of ubiquitin-like proteins: SUMO (smt3 homologue) (see Swiss:Q02724), Nedd8 (see Swiss:P29595), Elongin B (see Swiss:Q15370), Rub1 (see Swiss:Q9SHE7), and Parkin (see Swiss:O60260). A number of them are thought to carry a distinctive five-residue motif termed the proteasome-interacting motif (PIM), which may have a biologically significant role in protein delivery to proteasomes and recruitment of proteasomes to transcription sites [5].	Domain
B [auth H], E, H [auth B], K	PF03931	Skp1 family, tetramerisation domain (Skp1_POZ)	Skp1 family, tetramerisation domain	-	Domain
C [auth I], F, I [auth C], L	PF17211	VHL box domain (VHL_C)	VHL box domain	This domain represents the short C-terminal alpha helical domain from the VHL protein [1].	Domain
C [auth I], F, I [auth C], L	PF01847	VHL beta domain (VHL)	VHL beta domain	VHL forms a ternary complex with the elonginB Swiss:O44226 and elonginC Swiss:O13292 proteins. This complex binds Cul2, which then is involved in regulation of vascular endothelial growth factor Swiss:P15692 mRNA.	Domain

Gene Ontology: Gene Product Annotation Gene Ontology Database Homepage

Chains	Polymer	Molecular Function	Biological Process	Cellular Component
A [auth G], D, G [auth A], J	Elongin-B	transcription factor binding transcription coregulator binding transcription corepressor binding protein binding binding ubiquitin protein ligase binding ubiquitin-like protein ligase binding enzyme binding	cellular component organization cellular component biogenesis cellular component assembly protein-containing complex organization protein-containing complex assembly cellular process cellular component organization or biogenesis regulation of cellular process negative regulation of biological process positive regulation of macromolecule biosynthetic process nucleobase-containing compound metabolic process post-transcriptional regulation of gene expression positive regulation of metabolic process positive regulation of macromolecule metabolic process cellular component organization cellular component biogenesis cellular component assembly protein-containing complex organization protein-containing complex assembly cellular process cellular component organization or biogenesis regulation of cellular process negative regulation of biological process positive regulation of macromolecule biosynthetic process nucleobase-containing compound metabolic process post-transcriptional regulation of gene expression positive regulation of metabolic process positive regulation of macromolecule metabolic process miRNA metabolic process RNA catabolic process regulation of biological process negative regulation of metabolic process primary metabolic process nucleobase-containing compound catabolic process miRNA-mediated post-transcriptional gene silencing regulation of gene expression negative regulation of gene expression biosynthetic process negative regulation of miRNA-mediated gene silencing negative regulation of macromolecule biosynthetic process post-transcriptional gene silencing nucleic acid catabolic process regulation of macromolecule biosynthetic process metabolic process macromolecule metabolic process negative regulation of post-transcriptional gene silencing regulation of metabolic process catabolic process positive regulation of biological process RNA metabolic process regulation of miRNA-mediated gene silencing macromolecule catabolic process negative regulation of post-transcriptional gene silencing by regulatory ncRNA regulation of gene silencing by regulatory ncRNA positive regulation of biosynthetic process negative regulation of cellular process regulation of post-transcriptional gene silencing by regulatory ncRNA positive regulation of cellular process negative regulation of macromolecule metabolic process regulation of biosynthetic process negative regulation of gene silencing by regulatory ncRNA biological regulation regulation of macromolecule metabolic process miRNA catabolic process gene expression macromolecule biosynthetic process regulatory ncRNA-mediated post-transcriptional gene silencing nucleic acid metabolic process target-directed miRNA degradation regulatory ncRNA-mediated gene silencing regulation of post-transcriptional gene silencing negative regulation of biosynthetic process positive regulation of gene expression nucleobase-containing compound biosynthetic process DNA-templated transcription initiation RNA biosynthetic process DNA-templated transcription nucleic acid biosynthetic process transcription by RNA polymerase II transcription initiation at RNA polymerase II promoter transcription elongation by RNA polymerase II DNA-templated transcription elongation positive regulation of proteasomal protein catabolic process positive regulation of protein metabolic process proteolysis involved in protein catabolic process proteasome-mediated ubiquitin-dependent protein catabolic process regulation of ubiquitin-dependent protein catabolic process regulation of primary metabolic process positive regulation of ubiquitin-dependent protein catabolic process regulation of proteolysis regulation of proteolysis involved in protein catabolic process modification-dependent macromolecule catabolic process proteolysis protein metabolic process regulation of protein metabolic process proteasomal protein catabolic process protein catabolic process regulation of catabolic process positive regulation of protein catabolic process positive regulation of proteolysis involved in protein catabolic process positive regulation of catabolic process regulation of proteasomal ubiquitin-dependent protein catabolic process modification-dependent protein catabolic process positive regulation of proteolysis regulation of proteasomal protein catabolic process positive regulation of proteasomal ubiquitin-dependent protein catabolic process ubiquitin-dependent protein catabolic process regulation of protein catabolic process protein ubiquitination macromolecule modification post-translational protein modification protein modification process protein modification by small protein conjugation protein modification by small protein conjugation or removal	membrane-bounded organelle protein-containing complex intracellular anatomical structure transcription elongation factor complex nucleus membrane-enclosed lumen nuclear protein-containing complex intracellular membrane-bounded organelle elongin complex intracellular organelle lumen intracellular organelle cellular anatomical structure nucleoplasm organelle lumen membrane-bounded organelle protein-containing complex intracellular anatomical structure transcription elongation factor complex nucleus membrane-enclosed lumen nuclear protein-containing complex intracellular membrane-bounded organelle elongin complex intracellular organelle lumen intracellular organelle cellular anatomical structure nucleoplasm organelle lumen organelle nuclear lumen cytoplasm cytosol cytoplasmic ubiquitin ligase complex ubiquitin ligase complex catalytic complex transferase complex intracellular protein-containing complex VCB complex cullin-RING ubiquitin ligase complex Cul5-RING ubiquitin ligase complex Cul2-RING ubiquitin ligase complex
B [auth H], E, H [auth B], K	Elongin-C	transcription factor binding transcription coregulator binding transcription corepressor binding protein binding binding protein-macromolecule adaptor activity molecular adaptor activity	catabolic process proteolysis involved in protein catabolic process primary metabolic process protein catabolic process macromolecule catabolic process modification-dependent macromolecule catabolic process modification-dependent protein catabolic process proteolysis ubiquitin-dependent protein catabolic process metabolic process cellular process protein metabolic process macromolecule metabolic process regulation of cellular process catabolic process proteolysis involved in protein catabolic process primary metabolic process protein catabolic process macromolecule catabolic process modification-dependent macromolecule catabolic process modification-dependent protein catabolic process proteolysis ubiquitin-dependent protein catabolic process metabolic process cellular process protein metabolic process macromolecule metabolic process regulation of cellular process negative regulation of biological process positive regulation of macromolecule biosynthetic process nucleobase-containing compound metabolic process post-transcriptional regulation of gene expression positive regulation of metabolic process positive regulation of macromolecule metabolic process miRNA metabolic process RNA catabolic process regulation of biological process negative regulation of metabolic process nucleobase-containing compound catabolic process miRNA-mediated post-transcriptional gene silencing regulation of gene expression negative regulation of gene expression biosynthetic process negative regulation of miRNA-mediated gene silencing negative regulation of macromolecule biosynthetic process post-transcriptional gene silencing nucleic acid catabolic process regulation of macromolecule biosynthetic process negative regulation of post-transcriptional gene silencing regulation of metabolic process positive regulation of biological process RNA metabolic process regulation of miRNA-mediated gene silencing negative regulation of post-transcriptional gene silencing by regulatory ncRNA regulation of gene silencing by regulatory ncRNA positive regulation of biosynthetic process negative regulation of cellular process regulation of post-transcriptional gene silencing by regulatory ncRNA positive regulation of cellular process negative regulation of macromolecule metabolic process regulation of biosynthetic process negative regulation of gene silencing by regulatory ncRNA biological regulation regulation of macromolecule metabolic process miRNA catabolic process gene expression macromolecule biosynthetic process regulatory ncRNA-mediated post-transcriptional gene silencing nucleic acid metabolic process target-directed miRNA degradation regulatory ncRNA-mediated gene silencing regulation of post-transcriptional gene silencing negative regulation of biosynthetic process positive regulation of gene expression nucleobase-containing compound biosynthetic process DNA-templated transcription initiation RNA biosynthetic process DNA-templated transcription nucleic acid biosynthetic process transcription by RNA polymerase II transcription initiation at RNA polymerase II promoter regulation of primary metabolic process regulation of RNA metabolic process regulation of nucleobase-containing compound metabolic process regulation of RNA biosynthetic process regulation of transcription by RNA polymerase II regulation of DNA-templated transcription protein ubiquitination macromolecule modification post-translational protein modification protein modification process protein modification by small protein conjugation protein modification by small protein conjugation or removal	membrane-bounded organelle protein-containing complex intracellular anatomical structure transcription elongation factor complex nucleus membrane-enclosed lumen nuclear protein-containing complex intracellular membrane-bounded organelle elongin complex intracellular organelle lumen intracellular organelle cellular anatomical structure nucleoplasm organelle lumen membrane-bounded organelle protein-containing complex intracellular anatomical structure transcription elongation factor complex nucleus membrane-enclosed lumen nuclear protein-containing complex intracellular membrane-bounded organelle elongin complex intracellular organelle lumen intracellular organelle cellular anatomical structure nucleoplasm organelle lumen organelle nuclear lumen cytoplasm cytosol cullin-RING ubiquitin ligase complex ubiquitin ligase complex catalytic complex transferase complex intracellular protein-containing complex Cul5-RING ubiquitin ligase complex Cul2-RING ubiquitin ligase complex
C [auth I], F, I [auth C], L	von Hippel-Lindau disease tumor suppressor	ubiquitin-like ligase-substrate adaptor activity enzyme-substrate adaptor activity protein-macromolecule adaptor activity molecular adaptor activity transcription corepressor activity transcription regulator activity transcription coregulator activity transcription factor binding protein binding binding DNA-binding transcription factor binding transcription elongation factor activity aminoacyltransferase activity ubiquitin-like protein transferase activity ubiquitin-like ligase-substrate adaptor activity enzyme-substrate adaptor activity protein-macromolecule adaptor activity molecular adaptor activity transcription corepressor activity transcription regulator activity transcription coregulator activity transcription factor binding protein binding binding DNA-binding transcription factor binding transcription elongation factor activity aminoacyltransferase activity ubiquitin-like protein transferase activity catalytic activity, acting on a protein acyltransferase activity transferase activity catalytic activity ubiquitin-protein transferase activity enzyme binding	cellular response to stimulus regulation of signaling regulation of biological process regulation of cellular process response to stimulus negative regulation of signaling signaling negative regulation of response to stimulus biological regulation negative regulation of biological process regulation of signal transduction negative regulation of signal transduction negative regulation of cell communication cell communication regulation of response to stimulus cellular response to stimulus regulation of signaling regulation of biological process regulation of cellular process response to stimulus negative regulation of signaling signaling negative regulation of response to stimulus biological regulation negative regulation of biological process regulation of signal transduction negative regulation of signal transduction negative regulation of cell communication cell communication regulation of response to stimulus negative regulation of cellular process regulation of cell communication cellular process signal transduction regulation of protein stability regulation of biological quality protein stabilization negative regulation of programmed cell death regulation of apoptotic process regulation of programmed cell death cell death negative regulation of apoptotic process apoptotic process programmed cell death response to decreased oxygen levels cellular response to oxygen levels cellular response to hypoxia cellular response to decreased oxygen levels cellular response to chemical stimulus cellular response to stress response to hypoxia response to stress response to chemical response to oxygen levels response to abiotic stimulus cellular component organization metabolic process primary metabolic process protein metabolic process macromolecule metabolic process cellular component organization or biogenesis supramolecular fiber organization amyloid fibril formation regulation of biosynthetic process regulation of macromolecule metabolic process gene expression macromolecule biosynthetic process regulation of gene expression biosynthetic process regulation of macromolecule biosynthetic process regulation of metabolic process transcription elongation by RNA polymerase II RNA metabolic process negative regulation of transcription elongation by RNA polymerase II 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 transcription by RNA polymerase II 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 DNA-templated transcription elongation negative regulation of DNA-templated transcription regulation of transcription elongation by RNA polymerase II negative regulation of metabolic process nucleobase-containing compound biosynthetic process nucleic acid metabolic process negative regulation of DNA-templated transcription, elongation DNA-templated transcription elongation negative regulation of biosynthetic process negative regulation of macromolecule biosynthetic process regulation of DNA-templated transcription negative regulation of RNA metabolic process protein ubiquitination macromolecule modification post-translational protein modification protein modification process protein modification by small protein conjugation protein modification by small protein conjugation or removal developmental process regulation of developmental process cellular developmental process positive regulation of biological process regulation of cell differentiation positive regulation of developmental process positive regulation of cell differentiation cell differentiation positive regulation of cellular process catabolic process proteolysis involved in protein catabolic process proteasomal protein catabolic process protein catabolic process proteasome-mediated ubiquitin-dependent protein catabolic process macromolecule catabolic process modification-dependent macromolecule catabolic process modification-dependent protein catabolic process proteolysis ubiquitin-dependent protein catabolic process cell surface receptor signaling pathway via STAT regulation of receptor signaling pathway via JAK-STAT negative regulation of receptor signaling pathway via JAK-STAT cell surface receptor signaling pathway negative regulation of receptor signaling pathway via STAT regulation of receptor signaling pathway via STAT cell surface receptor signaling pathway via JAK-STAT regulation of cellular response to hypoxia regulation of cellular response to stress regulation of response to stress anatomical structure morphogenesis anatomical structure development cell morphogenesis negative regulation of cell population proliferation cell population proliferation regulation of cell population proliferation negative regulation of catabolic process autophagy regulation of catabolic process regulation of autophagy negative regulation of autophagy process utilizing autophagic mechanism negative regulation of intracellular signal transduction intracellular signal transduction negative regulation of TORC1 signaling regulation of intracellular signal transduction negative regulation of TOR signaling regulation of TORC1 signaling TOR signaling regulation of TOR signaling TORC1 signaling positive regulation of DNA-templated transcription positive regulation of macromolecule biosynthetic process positive regulation of metabolic process positive regulation of biosynthetic process positive regulation of macromolecule metabolic process positive regulation of nucleobase-containing compound metabolic process positive regulation of RNA metabolic process positive regulation of RNA biosynthetic process negative regulation of gene expression regulation of transcription by RNA polymerase II negative regulation of transcription by RNA polymerase II	membrane-bounded organelle intracellular organelle cellular anatomical structure intracellular anatomical structure mitochondrion organelle cytoplasm intracellular membrane-bounded organelle cytosol cell periphery plasma membrane membrane membraneless organelle intracellular membraneless organelle membrane-bounded organelle intracellular organelle cellular anatomical structure intracellular anatomical structure mitochondrion organelle cytoplasm intracellular membrane-bounded organelle cytosol cell periphery plasma membrane membrane membraneless organelle intracellular membraneless organelle nucleus membrane-enclosed lumen intracellular organelle lumen nucleoplasm organelle lumen nuclear lumen endoplasmic reticulum endomembrane system

InterPro: Protein Family Classification InterPro Database Homepage

Chains	Accession	Name	Type
A [auth G], D, G [auth A], J	IPR000626	Ubiquitin-like domain	Domain
A [auth G], D, G [auth A], J	IPR039049	Elongin B	Family
A [auth G], D, G [auth A], J	IPR029071	Ubiquitin-like domain superfamily	Homologous Superfamily
B [auth H], E, H [auth B], K	IPR016073	SKP1 component, POZ domain	Domain
B [auth H], E, H [auth B], K	IPR001232	S-phase kinase-associated protein 1-like	Family
B [auth H], E, H [auth B], K	IPR039948	Elongin-C	Family
B [auth H], E, H [auth B], K	IPR011333	SKP1/BTB/POZ domain superfamily	Homologous Superfamily
C [auth I], F, I [auth C], L	IPR037139	von Hippel-Lindau disease tumour suppressor, alpha domain superfamily	Homologous Superfamily
C [auth I], F, I [auth C], L	IPR022772	von Hippel-Lindau disease tumour suppressor, beta/alpha domain	Domain
C [auth I], F, I [auth C], L	IPR024053	von Hippel-Lindau disease tumour suppressor, beta domain	Domain
C [auth I], F, I [auth C], L	IPR024048	von Hippel-Lindau disease tumour suppressor, alpha domain	Domain
C [auth I], F, I [auth C], L	IPR036208	VHL superfamily	Homologous Superfamily
C [auth I], F, I [auth C], L	IPR037140	von Hippel-Lindau disease tumour suppressor, beta domain superfamily	Homologous Superfamily

Pharos: Disease Associations Pharos Homepage Annotation

Chains	Drug Target	Associated Disease
A [auth G], D, G [auth A], J	Pharos: Q15370	acute myeloid leukemia ovarian cancer diabetes mellitus plasma cell myeloma lymphoplasmacytic lymphoma
B [auth H], E, H [auth B], K	Pharos: Q15369	papillary renal cell carcinoma sarcomatoid renal cell carcinoma collecting duct carcinoma chromophobe renal cell carcinoma renal cell carcinoma astrocytic tumor clear cell renal carcinoma dermatomyositis breast cancer invasive ductal breast carcinoma plasma cell myeloma Conventional (Clear Cell) Renal Cell Carcinoma ovarian cancer
C [auth I], F, I [auth C], L	Pharos: P40337	von Hippel-Lindau disease renal cell carcinoma kidney Wilms tumor Chuvash polycythemia familial polycythemia phaeochromocytoma Pheochromocytoma renal carcinoma sarcomatoid renal cell carcinoma kidney cancer microcystic adenoma nonpapillary renal cell carcinoma papillary adenoma clear cell renal carcinoma adenoma von Hippel-Lindau disease renal cell carcinoma kidney Wilms tumor Chuvash polycythemia familial polycythemia phaeochromocytoma Pheochromocytoma renal carcinoma sarcomatoid renal cell carcinoma kidney cancer microcystic adenoma nonpapillary renal cell carcinoma papillary adenoma clear cell renal carcinoma adenoma cancer papillary renal cell carcinoma chromophobe renal cell carcinoma collecting duct carcinoma sarcomatoid carcinoma follicular thyroid adenoma carcinoma paraganglioma erythropoietin polycythemia hemangioblastoma acquired polycythemia vera lung benign neoplasm adrenal medulla cancer benign neoplasm Perlman syndrome extra-adrenal sympathetic paraganglioma undifferentiated carcinoma hemangioma kidney neoplasm neuroendocrine carcinoma benign neoplasm of adrenal gland oligodendroglioma polycythemia diabetes mellitus hereditary Wilms tumor malignant ependymoma adrenal gland pheochromocytoma astrocytic tumor ovarian cancer

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.