Summary Structural details Experimental details Functional details Sequence Neighbor History Downloads

4BB5

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

Functional Information from GO Data

Chain	GOid	namespace	contents
A	0005496	molecular_function	steroid binding
A	0005783	cellular_component	endoplasmic reticulum
A	0005789	cellular_component	endoplasmic reticulum membrane
A	0006706	biological_process	steroid catabolic process
A	0008202	biological_process	steroid metabolic process
A	0016020	cellular_component	membrane
A	0016491	molecular_function	oxidoreductase activity
A	0030324	biological_process	lung development
A	0042803	molecular_function	protein homodimerization activity
A	0043231	cellular_component	intracellular membrane-bounded organelle
A	0047022	molecular_function	7-beta-hydroxysteroid dehydrogenase (NADP+) activity
A	0050661	molecular_function	NADP binding
A	0070524	molecular_function	11-beta-hydroxysteroid dehydrogenase (NADP+) activity
A	0102196	molecular_function	cortisol dehydrogenase activity
B	0005496	molecular_function	steroid binding
B	0005783	cellular_component	endoplasmic reticulum
B	0005789	cellular_component	endoplasmic reticulum membrane
B	0006706	biological_process	steroid catabolic process
B	0008202	biological_process	steroid metabolic process
B	0016020	cellular_component	membrane
B	0016491	molecular_function	oxidoreductase activity
B	0030324	biological_process	lung development
B	0042803	molecular_function	protein homodimerization activity
B	0043231	cellular_component	intracellular membrane-bounded organelle
B	0047022	molecular_function	7-beta-hydroxysteroid dehydrogenase (NADP+) activity
B	0050661	molecular_function	NADP binding
B	0070524	molecular_function	11-beta-hydroxysteroid dehydrogenase (NADP+) activity
B	0102196	molecular_function	cortisol dehydrogenase activity
C	0005496	molecular_function	steroid binding
C	0005783	cellular_component	endoplasmic reticulum
C	0005789	cellular_component	endoplasmic reticulum membrane
C	0006706	biological_process	steroid catabolic process
C	0008202	biological_process	steroid metabolic process
C	0016020	cellular_component	membrane
C	0016491	molecular_function	oxidoreductase activity
C	0030324	biological_process	lung development
C	0042803	molecular_function	protein homodimerization activity
C	0043231	cellular_component	intracellular membrane-bounded organelle
C	0047022	molecular_function	7-beta-hydroxysteroid dehydrogenase (NADP+) activity
C	0050661	molecular_function	NADP binding
C	0070524	molecular_function	11-beta-hydroxysteroid dehydrogenase (NADP+) activity
C	0102196	molecular_function	cortisol dehydrogenase activity
D	0005496	molecular_function	steroid binding
D	0005783	cellular_component	endoplasmic reticulum
D	0005789	cellular_component	endoplasmic reticulum membrane
D	0006706	biological_process	steroid catabolic process
D	0008202	biological_process	steroid metabolic process
D	0016020	cellular_component	membrane
D	0016491	molecular_function	oxidoreductase activity
D	0030324	biological_process	lung development
D	0042803	molecular_function	protein homodimerization activity
D	0043231	cellular_component	intracellular membrane-bounded organelle
D	0047022	molecular_function	7-beta-hydroxysteroid dehydrogenase (NADP+) activity
D	0050661	molecular_function	NADP binding
D	0070524	molecular_function	11-beta-hydroxysteroid dehydrogenase (NADP+) activity
D	0102196	molecular_function	cortisol dehydrogenase activity

Functional Information from PDB Data

site_id	AC1
Number of Residues	34
Details	BINDING SITE FOR RESIDUE NAP A 1290

Chain	Residue
A	GLY41
A	THR92
A	MET93
A	ASN119
A	ILE121
A	VAL168
A	SER169
A	SER170
A	TYR183
A	LYS187
A	LEU215
A	ALA42
A	GLY216
A	LEU217
A	ILE218
A	THR220
A	THR222
A	ALA223
A	HD21291
A	HOH2002
A	HOH2003
A	HOH2004
A	SER43
A	HOH2010
A	HOH2033
A	HOH2077
A	HOH2097
A	HOH2098
A	LYS44
A	GLY45
A	ILE46
A	ALA65
A	ARG66
A	SER67

site_id	AC2
Number of Residues	15
Details	BINDING SITE FOR RESIDUE HD2 A 1291

Chain	Residue
A	ILE121
A	THR124
A	SER170
A	LEU171
A	TYR183
A	LEU215
A	GLY216
A	LEU217
A	THR222
A	ALA226
A	VAL231
A	NAP1290
A	HOH2035
A	HOH2097
B	TYR284

site_id	AC3
Number of Residues	34
Details	BINDING SITE FOR RESIDUE NAP B 1290

Chain	Residue
B	GLY41
B	ALA42
B	SER43
B	GLY45
B	ILE46
B	ALA65
B	ARG66
B	SER67
B	THR92
B	MET93
B	ASN119
B	ILE121
B	VAL168
B	SER169
B	SER170
B	TYR183
B	LYS187
B	LEU215
B	GLY216
B	LEU217
B	ILE218
B	THR220
B	THR222
B	ALA223
B	HD21291
B	HOH2005
B	HOH2006
B	HOH2008
B	HOH2019
B	HOH2043
B	HOH2045
B	HOH2073
B	HOH2088
B	HOH2089

site_id	AC4
Number of Residues	16
Details	BINDING SITE FOR RESIDUE HD2 B 1291

Chain	Residue
A	TYR280
A	TYR284
B	THR124
B	SER170
B	LEU171
B	TYR177
B	TYR183
B	LEU215
B	GLY216
B	LEU217
B	THR222
B	ALA226
B	VAL231
B	NAP1290
B	HOH2046
B	HOH2088

site_id	AC5
Number of Residues	33
Details	BINDING SITE FOR RESIDUE NAP C 1280

Chain	Residue
C	GLY41
C	ALA42
C	SER43
C	LYS44
C	GLY45
C	ILE46
C	ALA65
C	ARG66
C	SER67
C	THR92
C	MET93
C	ASN119
C	ILE121
C	VAL168
C	SER169
C	SER170
C	TYR183
C	LYS187
C	LEU215
C	GLY216
C	LEU217
C	ILE218
C	THR220
C	THR222
C	ALA223
C	HD21281
C	HOH2008
C	HOH2009
C	HOH2010
C	HOH2022
C	HOH2074
C	HOH2089
C	HOH2090

site_id	AC6
Number of Residues	14
Details	BINDING SITE FOR RESIDUE HD2 C 1281

Chain	Residue
C	THR124
C	SER170
C	LEU171
C	TYR183
C	GLY216
C	LEU217
C	THR222
C	VAL231
C	MET233
C	NAP1280
C	HOH2044
C	HOH2089
D	TYR280
D	TYR284

site_id	AC7
Number of Residues	28
Details	BINDING SITE FOR RESIDUE NAP D 1291

Chain	Residue
D	GLY41
D	ALA42
D	SER43
D	LYS44
D	GLY45
D	ILE46
D	ALA65
D	ARG66
D	SER67
D	THR92
D	MET93
D	ASN119
D	ILE121
D	VAL168
D	SER169
D	SER170
D	TYR183
D	LYS187
D	LEU215
D	GLY216
D	ILE218
D	THR220
D	THR222
D	ALA223
D	HD21292
D	HOH2001
D	HOH2002
D	HOH2009

site_id	AC8
Number of Residues	13
Details	BINDING SITE FOR RESIDUE HD2 D 1292

Chain	Residue
D	ILE121
D	THR124
D	SER170
D	LEU171
D	TYR177
D	TYR183
D	LEU215
D	GLY216
D	LEU217
D	THR222
D	ALA226
D	MET233
D	NAP1291

Functional Information from PROSITE/UniProt

site_id	PS00061
Number of Residues	29
Details	ADH_SHORT Short-chain dehydrogenases/reductases family signature. SlagkvayplVaaYSASKFALdGFFsSIR

Chain	Residue	Details
A	SER170-ARG198

Functional Information from SwissProt/UniProt

site_id	SWS_FT_FI1
Number of Residues	24
Details	TOPO_DOM: Cytoplasmic => ECO:0000255

Chain	Residue	Details
A	MET1-TYR7
B	MET1-TYR7
C	MET1-TYR7
D	MET1-TYR7

site_id	SWS_FT_FI2
Number of Residues	64
Details	TRANSMEM: Helical; Signal-anchor for type II membrane protein => ECO:0000255

Chain	Residue	Details
A	LEU8-ASN24
B	LEU8-ASN24
C	LEU8-ASN24
D	LEU8-ASN24

site_id	SWS_FT_FI3
Number of Residues	1068
Details	TOPO_DOM: Lumenal => ECO:0000255

Chain	Residue	Details
A	GLU25-LYS292
B	GLU25-LYS292
C	GLU25-LYS292
D	GLU25-LYS292

site_id	SWS_FT_FI4
Number of Residues	4
Details	ACT_SITE: Proton acceptor

Chain	Residue	Details
A	TYR183
B	TYR183
C	TYR183
D	TYR183

site_id	SWS_FT_FI5
Number of Residues	20
Details	BINDING: BINDING => ECO:0000269\|PubMed:15513927, ECO:0000269\|PubMed:17919905, ECO:0000269\|PubMed:18069989, ECO:0000269\|PubMed:18485702, ECO:0000269\|PubMed:18553955, ECO:0000269\|PubMed:19217779

Chain	Residue	Details
A	GLY41
B	ILE218
C	GLY41
C	THR92
C	ASN119
C	TYR183
C	ILE218
D	GLY41
D	THR92
D	ASN119
D	TYR183
A	THR92
D	ILE218
A	ASN119
A	TYR183
A	ILE218
B	GLY41
B	THR92
B	ASN119
B	TYR183

site_id	SWS_FT_FI6
Number of Residues	4
Details	BINDING: BINDING => ECO:0000269\|PubMed:15513927, ECO:0007744\|PDB:1XU7, ECO:0007744\|PDB:1XU9

Chain	Residue	Details
A	SER170
B	SER170
C	SER170
D	SER170

site_id	SWS_FT_FI7
Number of Residues	8
Details	CARBOHYD: N-linked (GlcNAc...) asparagine => ECO:0000269\|PubMed:19159218

Chain	Residue	Details
A	ASN123
A	ASN162
B	ASN123
B	ASN162
C	ASN123
C	ASN162
D	ASN123
D	ASN162

site_id	SWS_FT_FI8
Number of Residues	4
Details	CARBOHYD: N-linked (GlcNAc...) asparagine => ECO:0000255

Chain	Residue	Details
A	ASN207
B	ASN207
C	ASN207
D	ASN207

		Sequence (fasta)
		PDBx/mmCIF
		PDBML format (no-atom)
		PDB format (full)
		Validation report (PDF)
		EDMap 2fo-fc (MTZ)