5V9T

Crystal structure of selective pyrrolidine amide KDM5a inhibitor N-{(3R)-1-[3-(propan-2-yl)-1H-pyrazole-5-carbonyl]pyrrolidin-3-yl}cyclopropanecarboxamide (compound 48)

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	SCOP2B Superfamily	ARID-like	8074032	3001026	SCOP2B (2022-06-29)
B	SCOP2B Superfamily	ARID-like	8074032	3001026	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	KOG1246_1st,JmjC	e5v9tA3	A: beta sandwiches	X: jelly-roll	H: Double-stranded beta-helix (From Topology)	T: Double-stranded beta-helix	F: KOG1246_1st,JmjC	ECOD (1.6)
A	ARID	e5v9tA2	A: alpha arrays	X: HTH	H: HTH	T: tri-helical	F: ARID	ECOD (1.6)
A	zf-C5HC2,KOG1246_1st	e5v9tA1	A: few secondary structure elements	X: Glucocorticoid receptor-like	H: LIM domain-like	T: LIM domain-like	F: zf-C5HC2,KOG1246_1st	ECOD (1.6)
B	JmjC	e5v9tB4	A: beta sandwiches	X: jelly-roll	H: Double-stranded beta-helix (From Topology)	T: Double-stranded beta-helix	F: JmjC	ECOD (1.6)
B	ARID	e5v9tB5	A: alpha arrays	X: HTH	H: HTH	T: tri-helical	F: ARID	ECOD (1.6)
B	zf-C5HC2	e5v9tB3	A: few secondary structure elements	X: Glucocorticoid receptor-like	H: LIM domain-like	T: LIM domain-like	F: zf-C5HC2	ECOD (1.6)

Protein Family Annotation Pfam Database Homepage

Chains	Accession	Name	Description	Comments	Source
A, B	PF21323	Lysine-specific demethylase 5, C-terminal helical domain (KDM5_C-hel)	Lysine-specific demethylase 5, C-terminal helical domain	This is the C-terminal helical domain from Lysine-specific demethylase 5 subfamily (KDM5), which is localised between the Jumonji C (JmjC) domain and the C5HC2 zinc finger motif (Pfam:PF02928) [1-5].	Domain
A, B	PF02928	C5HC2 zinc finger (zf-C5HC2)	C5HC2 zinc finger	Predicted zinc finger with eight potential zinc ligand binding residues. This domain is found in Jumonji [1]. This domain may have a DNA binding function.	Domain
A, B	PF02373	JmjC domain, hydroxylase (JmjC)	JmjC domain, hydroxylase	The JmjC domain belongs to the Cupin superfamily [3]. JmjC-domain proteins may be protein hydroxylases that catalyse a novel histone modification [4]. This is confirmed to be a hydroxylase: the human JmjC protein named Tyw5p unexpectedly acts in the ...	The JmjC domain belongs to the Cupin superfamily [3]. JmjC-domain proteins may be protein hydroxylases that catalyse a novel histone modification [4]. This is confirmed to be a hydroxylase: the human JmjC protein named Tyw5p unexpectedly acts in the biosynthesis of a hypermodified nucleoside, hydroxy-wybutosine, in tRNA-Phe by catalysing hydroxylation [5].	Domain
A, B	PF02375	jmjN domain (JmjN)	jmjN domain	-	Family
A, B	PF08429	PLU-1-like protein (PLU-1)	PLU-1-like protein	-	Family
A, B	PF01388	ARID/BRIGHT DNA binding domain (ARID)	ARID/BRIGHT DNA binding domain	This domain is know as ARID for AT-Rich Interaction Domain [1], and also known as the BRIGHT domain [3].	Domain

Gene Ontology: Gene Product Annotation Gene Ontology Database Homepage

Chains	Polymer	Molecular Function	Biological Process	Cellular Component
A, B	Lysine-specific demethylase 5A	protein binding binding histone binding DNA binding sequence-specific DNA binding sequence-specific double-stranded DNA binding transcription cis-regulatory region binding double-stranded DNA binding organic cyclic compound binding nucleic acid binding transcription regulatory region nucleic acid binding enzyme regulator activity molecular function inhibitor activity molecular function regulator activity protein binding binding histone binding DNA binding sequence-specific DNA binding sequence-specific double-stranded DNA binding transcription cis-regulatory region binding double-stranded DNA binding organic cyclic compound binding nucleic acid binding transcription regulatory region nucleic acid binding enzyme regulator activity molecular function inhibitor activity molecular function regulator activity enzyme inhibitor activity transcription coactivator activity transcription regulator activity transcription coregulator activity protein-macromolecule adaptor activity molecular adaptor activity protein-containing complex binding chromatin binding chromatin DNA binding catalytic activity, acting on a protein protein demethylase activity histone modifying activity histone demethylase activity catalytic activity demethylase activity cation binding transition metal ion binding zinc ion binding ion binding metal ion binding small molecule binding histone H3K4me/H3K4me2/H3K4me3 demethylase activity oxidoreductase activity, acting on paired donors, with incorporation or reduction of molecular oxygen dioxygenase activity oxidoreductase activity histone H3 demethylase activity 2-oxoglutarate-dependent dioxygenase activity histone H3K4 demethylase activity methylated histone binding modification-dependent protein binding methylation-dependent protein binding	regulation of cellular process cellular biosynthetic process RNA metabolic process regulation of primary metabolic process nucleobase-containing compound metabolic process RNA biosynthetic process nucleic acid biosynthetic process DNA-templated transcription regulation of RNA metabolic process organic substance metabolic process organic substance biosynthetic process regulation of nucleobase-containing compound metabolic process regulation of RNA biosynthetic process regulation of biosynthetic process regulation of cellular process cellular biosynthetic process RNA metabolic process regulation of primary metabolic process nucleobase-containing compound metabolic process RNA biosynthetic process nucleic acid biosynthetic process DNA-templated transcription regulation of RNA metabolic process organic substance metabolic process organic substance biosynthetic process regulation of nucleobase-containing compound metabolic process regulation of RNA biosynthetic process regulation of biosynthetic process regulation of biological process cellular metabolic process biological regulation primary metabolic process regulation of cellular metabolic process regulation of macromolecule metabolic process nucleobase-containing compound biosynthetic process gene expression macromolecule biosynthetic process nucleic acid metabolic process regulation of cellular biosynthetic process organic cyclic compound metabolic process regulation of gene expression regulation of molecular function biosynthetic process regulation of DNA-binding transcription factor activity organic cyclic compound biosynthetic process metabolic process regulation of macromolecule biosynthetic process cellular process regulation of DNA-templated transcription macromolecule metabolic process regulation of metabolic process rhythmic process circadian regulation of gene expression circadian rhythm negative regulation of biological process negative regulation of cellular metabolic process protein-DNA complex organization cellular component organization chromatin organization negative regulation of cellular process chromatin remodeling cellular component organization or biogenesis negative regulation of macromolecule metabolic process heterochromatin formation protein-containing complex organization epigenetic regulation of gene expression negative regulation of metabolic process negative regulation of cellular biosynthetic process negative regulation of gene expression negative regulation of biosynthetic process negative regulation of macromolecule biosynthetic process facultative heterochromatin formation negative regulation of gene expression, epigenetic positive regulation of macromolecule biosynthetic process positive regulation of metabolic process positive regulation of macromolecule metabolic process positive regulation of nucleobase-containing compound metabolic process positive regulation of RNA metabolic process positive regulation of DNA-templated transcription positive regulation of biological process positive regulation of cellular metabolic process positive regulation of biosynthetic process positive regulation of cellular process positive regulation of RNA biosynthetic process positive regulation of cellular biosynthetic process negative regulation of RNA biosynthetic process transcription by RNA polymerase II negative regulation of nucleobase-containing compound metabolic process regulation of transcription by RNA polymerase II negative regulation of DNA-templated transcription negative regulation of transcription by RNA polymerase II negative regulation of RNA metabolic process	membrane-bounded organelle intracellular anatomical structure nucleus membrane-enclosed lumen intracellular membrane-bounded organelle cellular anatomical entity nucleolus intracellular organelle lumen intracellular organelle organelle lumen organelle intracellular non-membrane-bounded organelle nuclear lumen non-membrane-bounded organelle membrane-bounded organelle intracellular anatomical structure nucleus membrane-enclosed lumen intracellular membrane-bounded organelle cellular anatomical entity nucleolus intracellular organelle lumen intracellular organelle organelle lumen organelle intracellular non-membrane-bounded organelle nuclear lumen non-membrane-bounded organelle nucleoplasm protein-containing complex protein-DNA complex chromatin chromosome
C [auth G]	Lysine-specific demethylase 5A	-	-	-

InterPro: Protein Family Classification InterPro Database Homepage

Chains	Accession	Name	Type
A, B	IPR001965	Zinc finger, PHD-type	Domain
A, B	IPR048615	Lysine-specific demethylase 5, C-terminal helical domain	Domain
A, B	IPR003347	JmjC domain	Domain
A, B	IPR003349	JmjN domain	Domain
A, B	IPR001606	ARID DNA-binding domain	Domain
A, B	IPR019787	Zinc finger, PHD-finger	Domain
A, B	IPR011011	Zinc finger, FYVE/PHD-type	Homologous Superfamily
A, B	IPR047970	Lysine-specific demethylase 5A, second PHD finger	Domain
A, B	IPR019786	Zinc finger, PHD-type, conserved site	Conserved Site
A, B	IPR047973	Lysine-specific demethylase 5A, first PHD-finger	Domain
A, B	IPR013637	Lysine-specific demethylase-like domain	Domain
A, B	IPR047972	Lysine-specific demethylase 5A, third PHD-finger	Domain
A, B	IPR013083	Zinc finger, RING/FYVE/PHD-type	Homologous Superfamily
A, B	IPR004198	Zinc finger, C5HC2-type	Domain
A, B	IPR036431	ARID DNA-binding domain superfamily	Homologous Superfamily
A, B	IPR047974	Lysine-specific demethylase 5A, ARID domain	Domain

Pharos: Disease Associations Pharos Homepage Annotation

Chains	Drug Target	Associated Disease
A, B	Pharos: P29375	intellectual disability pancreatic intraductal papillary-mucinous neoplasm with low grade dysplasia Profound Mental Retardation tuberculosis Alzheimer disease autism spectrum disorder glioblastoma large cell medulloblastoma medulloblastoma osteosarcoma pancreatic intraductal papillary-mucinous carcinoma Pick disease psoriasis ulcerative colitis astrocytic tumor intellectual disability pancreatic intraductal papillary-mucinous neoplasm with low grade dysplasia Profound Mental Retardation tuberculosis Alzheimer disease autism spectrum disorder glioblastoma large cell medulloblastoma medulloblastoma osteosarcoma pancreatic intraductal papillary-mucinous carcinoma Pick disease psoriasis ulcerative colitis astrocytic tumor breast cancer hepatocellular carcinoma malignant ependymoma ovarian cancer pancreatic intraductal papillary-mucinous neoplasm primitive neuroectodermal tumor rheumatoid arthritis atypical teratoid rhabdoid tumor dermatomyositis malignant glioma pancreatic ductal adenocarcinoma

RCSB PDB Core Operations are funded by the National Science Foundation (DBI-1832184), 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 R01GM133198.