4BB5

Free-Wilson and Structural Approaches to Co-optimising Human and Rodent Isoform Potency for 11b-Hydroxysteroid Dehydrogenase Type 1 11b-HSD1 Inhibitors

External Resource: Annotation

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

Domain Annotation: SCOP/SCOPe Classification SCOP-e Database Homepage

Chains	Domain Info	Class	Fold	Superfamily	Family	Domain	Species	Provenance Source (Version)
A	d4bb5a_	Alpha and beta proteins (a/b)	NAD(P)-binding Rossmann-fold domains	NAD(P)-binding Rossmann-fold domains	Tyrosine-dependent oxidoreductases	automated matches	HUMAN (Homo sapiens ) [TaxId: 9606 ],	SCOPe (2.08)
C	d4bb5c_	Alpha and beta proteins (a/b)	NAD(P)-binding Rossmann-fold domains	NAD(P)-binding Rossmann-fold domains	Tyrosine-dependent oxidoreductases	automated matches	HUMAN (Homo sapiens ) [TaxId: 9606 ],	SCOPe (2.08)
B	d4bb5b_	Alpha and beta proteins (a/b)	NAD(P)-binding Rossmann-fold domains	NAD(P)-binding Rossmann-fold domains	Tyrosine-dependent oxidoreductases	automated matches	HUMAN (Homo sapiens ) [TaxId: 9606 ],	SCOPe (2.08)
D	d4bb5d_	Alpha and beta proteins (a/b)	NAD(P)-binding Rossmann-fold domains	NAD(P)-binding Rossmann-fold domains	Tyrosine-dependent oxidoreductases	automated matches	HUMAN (Homo sapiens ) [TaxId: 9606 ],	SCOPe (2.08)

Domain Annotation: SCOP2 Classification SCOP2 Database Homepage

Chains	Type	Family Name	Domain Identifier	Family Identifier	Provenance Source (Version)
A	SCOP2B Superfamily	SDR-like	8057143	3000038	SCOP2B (2022-06-29)
C	SCOP2B Superfamily	SDR-like	8057143	3000038	SCOP2B (2022-06-29)
B	SCOP2B Superfamily	SDR-like	8057143	3000038	SCOP2B (2022-06-29)
D	SCOP2B Superfamily	SDR-like	8057143	3000038	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	adh_short_C2	e4bb5A2	A: a/b three-layered sandwiches	X: Rossmann-like	H: Rossmann-related	T: NAD(P)-binding Rossmann-fold domains	F: adh_short_C2	ECOD (1.6)
C	adh_short_C2	e4bb5C2	A: a/b three-layered sandwiches	X: Rossmann-like	H: Rossmann-related	T: NAD(P)-binding Rossmann-fold domains	F: adh_short_C2	ECOD (1.6)
B	adh_short_C2	e4bb5B2	A: a/b three-layered sandwiches	X: Rossmann-like	H: Rossmann-related	T: NAD(P)-binding Rossmann-fold domains	F: adh_short_C2	ECOD (1.6)
D	adh_short_C2	e4bb5D2	A: a/b three-layered sandwiches	X: Rossmann-like	H: Rossmann-related	T: NAD(P)-binding Rossmann-fold domains	F: adh_short_C2	ECOD (1.6)

Domain Annotation: CATH CATH Database Homepage

Chain	Domain	Class	Architecture	Topology	Homology	Provenance Source (Version)
A	3.40.50.720	Alpha Beta	3-Layer(aba) Sandwich	Rossmann fold	NAD(P)-binding Rossmann-like Domain	CATH (4.3.0)
C	3.40.50.720	Alpha Beta	3-Layer(aba) Sandwich	Rossmann fold	NAD(P)-binding Rossmann-like Domain	CATH (4.3.0)
B	3.40.50.720	Alpha Beta	3-Layer(aba) Sandwich	Rossmann fold	NAD(P)-binding Rossmann-like Domain	CATH (4.3.0)
D	3.40.50.720	Alpha Beta	3-Layer(aba) Sandwich	Rossmann fold	NAD(P)-binding Rossmann-like Domain	CATH (4.3.0)

Protein Family Annotation Pfam Database Homepage

Chains	Accession	Name	Description	Comments	Source
A, B, C, D	PF00106	short chain dehydrogenase (adh_short)	short chain dehydrogenase	This family contains a wide variety of dehydrogenases.	Domain

Gene Ontology: Gene Product Annotation Gene Ontology Database Homepage

Chains	Polymer	Molecular Function	Biological Process	Cellular Component
A, B, C, D	CORTICOSTEROID 11-BETA-DEHYDROGENASE ISOZYME 1	binding nucleoside phosphate binding purine nucleotide binding organic cyclic compound binding adenyl nucleotide binding nucleotide binding heterocyclic compound binding NADP binding small molecule binding identical protein binding protein binding protein homodimerization activity protein dimerization activity steroid dehydrogenase activity binding nucleoside phosphate binding purine nucleotide binding organic cyclic compound binding adenyl nucleotide binding nucleotide binding heterocyclic compound binding NADP binding small molecule binding identical protein binding protein binding protein homodimerization activity protein dimerization activity steroid dehydrogenase activity oxidoreductase activity oxidoreductase activity, acting on the CH-OH group of donors, NAD or NADP as acceptor 7-beta-hydroxysteroid dehydrogenase (NADP+) activity oxidoreductase activity, acting on CH-OH group of donors steroid dehydrogenase activity, acting on the CH-OH group of donors, NAD or NADP as acceptor catalytic activity 11-beta-hydroxysteroid dehydrogenase [NAD(P)+] activity cortisol dehydrogenase activity 11-beta-hydroxysteroid dehydrogenase (NADP+) activity steroid binding lipid binding	steroid catabolic process lipid catabolic process catabolic process steroid metabolic process metabolic process cellular process primary metabolic process lipid metabolic process developmental process multicellular organism development multicellular organismal process tube development anatomical structure development animal organ development steroid catabolic process lipid catabolic process catabolic process steroid metabolic process metabolic process cellular process primary metabolic process lipid metabolic process developmental process multicellular organism development multicellular organismal process tube development anatomical structure development animal organ development respiratory tube development lung development respiratory system development system development	cellular anatomical structure membrane membrane-bounded organelle intracellular organelle intracellular anatomical structure organelle intracellular membrane-bounded organelle organelle subcompartment endomembrane system endoplasmic reticulum subcompartment nuclear outer membrane-endoplasmic reticulum membrane network endoplasmic reticulum cytoplasm organelle membrane cellular anatomical structure membrane membrane-bounded organelle intracellular organelle intracellular anatomical structure organelle intracellular membrane-bounded organelle organelle subcompartment endomembrane system endoplasmic reticulum subcompartment nuclear outer membrane-endoplasmic reticulum membrane network endoplasmic reticulum cytoplasm organelle membrane endoplasmic reticulum membrane

InterPro: Protein Family Classification InterPro Database Homepage

Chains	Accession	Name	Type
A, B, C, D	IPR002347	Short-chain dehydrogenase/reductase SDR	Family
A, B, C, D	IPR020904	Short-chain dehydrogenase/reductase, conserved site	Conserved Site
A, B, C, D	IPR051253	11-beta-hydroxysteroid dehydrogenase	Family
A, B, C, D	IPR036291	NAD(P)-binding domain superfamily	Homologous Superfamily

Pharos: Disease Associations Pharos Homepage Annotation

Chains	Drug Target	Associated Disease
A, B, C, D	Pharos: P28845	obesity disorder Insulin Resistance cortisone reductase deficiency rheumatoid arthritis hypertensive disorder allergic contact dermatitis cortisone reductase deficiency 2 hyperglycemia inflammatory bowel disease interstitial cystitis malignant ependymoma malignant pancreatic neoplasm adrenal cortex adenoma osteosarcoma pancreatic intraductal papillary-mucinous carcinoma obesity disorder Insulin Resistance cortisone reductase deficiency rheumatoid arthritis hypertensive disorder allergic contact dermatitis cortisone reductase deficiency 2 hyperglycemia inflammatory bowel disease interstitial cystitis malignant ependymoma malignant pancreatic neoplasm adrenal cortex adenoma osteosarcoma pancreatic intraductal papillary-mucinous carcinoma breast carcinoma peptic ulcer disease cleft lip depressive disorder psoriasis gastric carcinoma lung adenocarcinoma malignant mesothelioma adrenal cortex carcinoma ovarian cancer astrocytic tumor pancreatic intraductal papillary-mucinous neoplasm breast fibroadenoma Pick disease head and neck cancer lung cancer non-small cell lung carcinoma pancreatic ductal adenocarcinoma atopic eczema pancreatic intraductal papillary-mucinous neoplasm with low grade dysplasia chronic obstructive pulmonary disease pituitary cancer ductal breast carcinoma in situ sarcoidosis ulcerative colitis

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.