Summary Structural details Experimental details Functional details Sequence Neighbor History Downloads

3GMD

Structure-based design of 7-Azaindole-pyrrolidines as inhibitors of 11beta-Hydroxysteroid-Dehydrogenase type I

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	0006704	biological_process	glucocorticoid biosynthetic process
A	0006706	biological_process	steroid catabolic process
A	0006713	biological_process	glucocorticoid catabolic process
A	0008202	biological_process	steroid metabolic process
A	0008212	biological_process	mineralocorticoid metabolic process
A	0016020	cellular_component	membrane
A	0016491	molecular_function	oxidoreductase activity
A	0030324	biological_process	lung development
A	0031965	cellular_component	nuclear membrane
A	0042803	molecular_function	protein homodimerization activity
A	0043231	cellular_component	intracellular membrane-bounded organelle
A	0043456	biological_process	regulation of pentose-phosphate shunt
A	0045177	cellular_component	apical part of cell
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	0006704	biological_process	glucocorticoid biosynthetic process
B	0006706	biological_process	steroid catabolic process
B	0006713	biological_process	glucocorticoid catabolic process
B	0008202	biological_process	steroid metabolic process
B	0008212	biological_process	mineralocorticoid metabolic process
B	0016020	cellular_component	membrane
B	0016491	molecular_function	oxidoreductase activity
B	0030324	biological_process	lung development
B	0031965	cellular_component	nuclear membrane
B	0042803	molecular_function	protein homodimerization activity
B	0043231	cellular_component	intracellular membrane-bounded organelle
B	0043456	biological_process	regulation of pentose-phosphate shunt
B	0045177	cellular_component	apical part of cell
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	0006704	biological_process	glucocorticoid biosynthetic process
C	0006706	biological_process	steroid catabolic process
C	0006713	biological_process	glucocorticoid catabolic process
C	0008202	biological_process	steroid metabolic process
C	0008212	biological_process	mineralocorticoid metabolic process
C	0016020	cellular_component	membrane
C	0016491	molecular_function	oxidoreductase activity
C	0030324	biological_process	lung development
C	0031965	cellular_component	nuclear membrane
C	0042803	molecular_function	protein homodimerization activity
C	0043231	cellular_component	intracellular membrane-bounded organelle
C	0043456	biological_process	regulation of pentose-phosphate shunt
C	0045177	cellular_component	apical part of cell
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	0006704	biological_process	glucocorticoid biosynthetic process
D	0006706	biological_process	steroid catabolic process
D	0006713	biological_process	glucocorticoid catabolic process
D	0008202	biological_process	steroid metabolic process
D	0008212	biological_process	mineralocorticoid metabolic process
D	0016020	cellular_component	membrane
D	0016491	molecular_function	oxidoreductase activity
D	0030324	biological_process	lung development
D	0031965	cellular_component	nuclear membrane
D	0042803	molecular_function	protein homodimerization activity
D	0043231	cellular_component	intracellular membrane-bounded organelle
D	0043456	biological_process	regulation of pentose-phosphate shunt
D	0045177	cellular_component	apical part of cell
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
E	0005496	molecular_function	steroid binding
E	0005783	cellular_component	endoplasmic reticulum
E	0005789	cellular_component	endoplasmic reticulum membrane
E	0006704	biological_process	glucocorticoid biosynthetic process
E	0006706	biological_process	steroid catabolic process
E	0006713	biological_process	glucocorticoid catabolic process
E	0008202	biological_process	steroid metabolic process
E	0008212	biological_process	mineralocorticoid metabolic process
E	0016020	cellular_component	membrane
E	0016491	molecular_function	oxidoreductase activity
E	0030324	biological_process	lung development
E	0031965	cellular_component	nuclear membrane
E	0042803	molecular_function	protein homodimerization activity
E	0043231	cellular_component	intracellular membrane-bounded organelle
E	0043456	biological_process	regulation of pentose-phosphate shunt
E	0045177	cellular_component	apical part of cell
E	0047022	molecular_function	7-beta-hydroxysteroid dehydrogenase (NADP+) activity
E	0050661	molecular_function	NADP binding
E	0070524	molecular_function	11-beta-hydroxysteroid dehydrogenase (NADP+) activity
E	0102196	molecular_function	cortisol dehydrogenase activity
F	0005496	molecular_function	steroid binding
F	0005783	cellular_component	endoplasmic reticulum
F	0005789	cellular_component	endoplasmic reticulum membrane
F	0006704	biological_process	glucocorticoid biosynthetic process
F	0006706	biological_process	steroid catabolic process
F	0006713	biological_process	glucocorticoid catabolic process
F	0008202	biological_process	steroid metabolic process
F	0008212	biological_process	mineralocorticoid metabolic process
F	0016020	cellular_component	membrane
F	0016491	molecular_function	oxidoreductase activity
F	0030324	biological_process	lung development
F	0031965	cellular_component	nuclear membrane
F	0042803	molecular_function	protein homodimerization activity
F	0043231	cellular_component	intracellular membrane-bounded organelle
F	0043456	biological_process	regulation of pentose-phosphate shunt
F	0045177	cellular_component	apical part of cell
F	0047022	molecular_function	7-beta-hydroxysteroid dehydrogenase (NADP+) activity
F	0050661	molecular_function	NADP binding
F	0070524	molecular_function	11-beta-hydroxysteroid dehydrogenase (NADP+) activity
F	0102196	molecular_function	cortisol dehydrogenase activity
G	0005496	molecular_function	steroid binding
G	0005783	cellular_component	endoplasmic reticulum
G	0005789	cellular_component	endoplasmic reticulum membrane
G	0006704	biological_process	glucocorticoid biosynthetic process
G	0006706	biological_process	steroid catabolic process
G	0006713	biological_process	glucocorticoid catabolic process
G	0008202	biological_process	steroid metabolic process
G	0008212	biological_process	mineralocorticoid metabolic process
G	0016020	cellular_component	membrane
G	0016491	molecular_function	oxidoreductase activity
G	0030324	biological_process	lung development
G	0031965	cellular_component	nuclear membrane
G	0042803	molecular_function	protein homodimerization activity
G	0043231	cellular_component	intracellular membrane-bounded organelle
G	0043456	biological_process	regulation of pentose-phosphate shunt
G	0045177	cellular_component	apical part of cell
G	0047022	molecular_function	7-beta-hydroxysteroid dehydrogenase (NADP+) activity
G	0050661	molecular_function	NADP binding
G	0070524	molecular_function	11-beta-hydroxysteroid dehydrogenase (NADP+) activity
G	0102196	molecular_function	cortisol dehydrogenase activity
H	0005496	molecular_function	steroid binding
H	0005783	cellular_component	endoplasmic reticulum
H	0005789	cellular_component	endoplasmic reticulum membrane
H	0006704	biological_process	glucocorticoid biosynthetic process
H	0006706	biological_process	steroid catabolic process
H	0006713	biological_process	glucocorticoid catabolic process
H	0008202	biological_process	steroid metabolic process
H	0008212	biological_process	mineralocorticoid metabolic process
H	0016020	cellular_component	membrane
H	0016491	molecular_function	oxidoreductase activity
H	0030324	biological_process	lung development
H	0031965	cellular_component	nuclear membrane
H	0042803	molecular_function	protein homodimerization activity
H	0043231	cellular_component	intracellular membrane-bounded organelle
H	0043456	biological_process	regulation of pentose-phosphate shunt
H	0045177	cellular_component	apical part of cell
H	0047022	molecular_function	7-beta-hydroxysteroid dehydrogenase (NADP+) activity
H	0050661	molecular_function	NADP binding
H	0070524	molecular_function	11-beta-hydroxysteroid dehydrogenase (NADP+) activity
H	0102196	molecular_function	cortisol dehydrogenase activity

Functional Information from PDB Data

site_id	AC1
Number of Residues	33
Details	BINDING SITE FOR RESIDUE NDP A 300

Chain	Residue
A	2M32
A	THR92
A	MET93
A	ASN119
A	HIS120
A	ILE121
A	VAL142
A	ILE168
A	SER169
A	SER170
A	TYR183
A	GLY41
A	LYS187
A	LEU215
A	GLY216
A	LEU217
A	ILE218
A	THR220
A	THR222
A	ALA223
A	HOH290
A	HOH297
A	SER43
A	HOH306
A	HOH310
A	HOH400
A	HOH468
A	LYS44
A	GLY45
A	ILE46
A	ARG66
A	SER67
A	GLY91

site_id	AC2
Number of Residues	11
Details	BINDING SITE FOR RESIDUE 2M3 A 2

Chain	Residue
A	THR124
A	SER170
A	TYR177
A	TYR183
A	GLY216
A	LEU217
A	THR222
A	ALA223
A	NDP300
A	HOH312
B	TYR284

site_id	AC3
Number of Residues	29
Details	BINDING SITE FOR RESIDUE NDP B 300

Chain	Residue
B	2M31
B	GLY41
B	SER43
B	LYS44
B	GLY45
B	ILE46
B	ARG66
B	SER67
B	THR92
B	MET93
B	ASN119
B	HIS120
B	ILE121
B	ILE168
B	SER169
B	SER170
B	TYR183
B	LYS187
B	LEU215
B	GLY216
B	LEU217
B	ILE218
B	THR220
B	THR222
B	ALA223
B	HOH292
B	HOH309
B	HOH315
B	HOH516

site_id	AC4
Number of Residues	6
Details	BINDING SITE FOR RESIDUE SO4 B 2

Chain	Residue
B	GLY45
B	ARG48
B	THR220
B	GLU221
B	LYS238
B	HOH309

site_id	AC5
Number of Residues	11
Details	BINDING SITE FOR RESIDUE 2M3 B 1

Chain	Residue
A	TYR284
B	THR124
B	LEU126
B	SER170
B	TYR177
B	TYR183
B	GLY216
B	LEU217
B	THR222
B	ALA223
B	NDP300

site_id	AC6
Number of Residues	32
Details	BINDING SITE FOR RESIDUE NDP C 300

Chain	Residue
C	MET93
C	ASN119
C	HIS120
C	ILE121
C	ARG138
C	ILE168
C	SER169
C	SER170
C	TYR183
C	LYS187
C	LEU215
C	GLY216
C	LEU217
C	ILE218
C	THR220
C	THR222
C	ALA223
C	HOH293
C	HOH302
C	HOH324
C	HOH394
C	HOH423
C	HOH520
C	2M34
C	GLY41
C	SER43
C	LYS44
C	GLY45
C	ILE46
C	ARG66
C	SER67
C	THR92

site_id	AC7
Number of Residues	5
Details	BINDING SITE FOR RESIDUE SO4 C 7

Chain	Residue
C	ARG66
C	GLN123
C	ARG138
C	HOH324
C	HOH459

site_id	AC8
Number of Residues	8
Details	BINDING SITE FOR RESIDUE SO4 C 8

Chain	Residue
C	HOH18
C	GLY45
C	ARG48
C	THR220
C	GLU221
C	LYS238
C	HOH346
C	HOH394

site_id	AC9
Number of Residues	15
Details	BINDING SITE FOR RESIDUE 2M3 C 4

Chain	Residue
C	THR124
C	LEU126
C	SER170
C	LEU171
C	TYR177
C	TYR183
C	LEU215
C	GLY216
C	LEU217
C	THR222
C	ALA223
C	ALA226
C	NDP300
C	HOH479
D	TYR284

site_id	BC1
Number of Residues	29
Details	BINDING SITE FOR RESIDUE NDP D 300

Chain	Residue
D	2M33
D	GLY41
D	SER43
D	LYS44
D	GLY45
D	ILE46
D	ALA65
D	ARG66
D	SER67
D	THR92
D	MET93
D	ASN119
D	HIS120
D	ILE121
D	ILE168
D	SER169
D	SER170
D	TYR183
D	LYS187
D	LEU215
D	GLY216
D	LEU217
D	ILE218
D	THR220
D	THR222
D	ALA223
D	HOH294
D	HOH310
D	HOH326

site_id	BC2
Number of Residues	9
Details	BINDING SITE FOR RESIDUE SO4 D 1

Chain	Residue
D	HOH10
D	LYS44
D	GLY45
D	ARG48
D	THR220
D	GLU221
D	LYS238
D	HOH310
D	HOH329

site_id	BC3
Number of Residues	14
Details	BINDING SITE FOR RESIDUE 2M3 D 3

Chain	Residue
C	TYR284
D	THR124
D	LEU126
D	SER170
D	TYR177
D	TYR183
D	LEU215
D	GLY216
D	LEU217
D	THR222
D	ALA223
D	ALA226
D	NDP300
D	HOH332

site_id	BC4
Number of Residues	32
Details	BINDING SITE FOR RESIDUE NDP E 300

Chain	Residue
E	2M37
E	GLY41
E	SER43
E	LYS44
E	GLY45
E	ILE46
E	ALA65
E	ARG66
E	SER67
E	THR92
E	MET93
E	ASN119
E	HIS120
E	ILE121
E	ILE168
E	SER169
E	SER170
E	TYR183
E	LYS187
E	LEU215
E	GLY216
E	LEU217
E	ILE218
E	THR220
E	THR222
E	ALA223
E	HOH291
E	HOH311
E	HOH316
E	HOH461
E	HOH475
E	HOH521

site_id	BC5
Number of Residues	5
Details	BINDING SITE FOR RESIDUE SO4 E 4

Chain	Residue
E	ARG66
E	THR122
E	GLN123
E	ARG138
E	HOH477

site_id	BC6
Number of Residues	13
Details	BINDING SITE FOR RESIDUE 2M3 E 7

Chain	Residue
E	THR124
E	LEU126
E	SER170
E	TYR177
E	TYR183
E	LEU215
E	GLY216
E	LEU217
E	THR222
E	ALA226
E	HOH299
E	NDP300
F	TYR284

site_id	BC7
Number of Residues	32
Details	BINDING SITE FOR RESIDUE NDP F 300

Chain	Residue
F	HOH11
F	GLY41
F	SER43
F	LYS44
F	GLY45
F	ILE46
F	ALA65
F	ARG66
F	SER67
F	THR92
F	MET93
F	ASN119
F	HIS120
F	ILE121
F	ILE168
F	SER169
F	SER170
F	TYR183
F	LYS187
F	LEU215
F	GLY216
F	LEU217
F	ILE218
F	THR220
F	THR222
F	ALA223
F	2M3290
F	HOH295
F	HOH308
F	HOH471
F	HOH472
F	HOH473

site_id	BC8
Number of Residues	6
Details	BINDING SITE FOR RESIDUE SO4 F 5

Chain	Residue
F	GLY45
F	ARG48
F	THR220
F	GLU221
F	LYS238
F	HOH323

site_id	BC9
Number of Residues	11
Details	BINDING SITE FOR RESIDUE 2M3 F 290

Chain	Residue
E	TYR284
F	ILE121
F	THR124
F	LEU126
F	SER170
F	TYR183
F	GLY216
F	LEU217
F	THR222
F	ALA223
F	NDP300

site_id	CC1
Number of Residues	29
Details	BINDING SITE FOR RESIDUE NDP G 300

Chain	Residue
G	2M38
G	GLY41
G	SER43
G	LYS44
G	GLY45
G	ILE46
G	ARG66
G	SER67
G	GLY91
G	THR92
G	MET93
G	ASN119
G	HIS120
G	ILE121
G	ILE168
G	SER169
G	SER170
G	TYR183
G	LYS187
G	LEU215
G	GLY216
G	LEU217
G	ILE218
G	THR220
G	THR222
G	ALA223
G	HOH308
G	HOH311
G	HOH392

site_id	CC2
Number of Residues	6
Details	BINDING SITE FOR RESIDUE SO4 G 9

Chain	Residue
G	LYS44
G	GLY45
G	ARG48
G	THR220
G	GLU221
G	LYS238

site_id	CC3
Number of Residues	12
Details	BINDING SITE FOR RESIDUE 2M3 G 8

Chain	Residue
G	ILE121
G	THR124
G	LEU126
G	SER170
G	TYR177
G	TYR183
G	GLY216
G	LEU217
G	THR222
G	ALA226
G	NDP300
H	TYR284

site_id	CC4
Number of Residues	30
Details	BINDING SITE FOR RESIDUE NDP H 300

Chain	Residue
H	GLY41
H	SER43
H	LYS44
H	GLY45
H	ILE46
H	ALA65
H	ARG66
H	SER67
H	THR92
H	MET93
H	ASN119
H	HIS120
H	ILE121
H	ILE168
H	SER169
H	SER170
H	TYR183
H	LYS187
H	LEU215
H	GLY216
H	LEU217
H	ILE218
H	THR220
H	THR222
H	ALA223
H	2M3290
H	HOH302
H	HOH307
H	HOH480
H	HOH481

site_id	CC5
Number of Residues	1
Details	BINDING SITE FOR RESIDUE SO4 H 3

Chain	Residue
H	LYS225

site_id	CC6
Number of Residues	6
Details	BINDING SITE FOR RESIDUE SO4 H 6

Chain	Residue
H	HOH9
H	GLY45
H	ARG48
H	GLU221
H	LYS238
H	HOH302

site_id	CC7
Number of Residues	14
Details	BINDING SITE FOR RESIDUE 2M3 H 290

Chain	Residue
G	TYR284
H	ILE121
H	THR124
H	SER125
H	LEU126
H	SER170
H	TYR177
H	TYR183
H	LEU215
H	GLY216
H	LEU217
H	THR222
H	ALA226
H	NDP300

Functional Information from PROSITE/UniProt

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

Chain	Residue	Details
A	SER170-ARG198

Functional Information from SwissProt/UniProt

site_id	SWS_FT_FI1
Number of Residues	8
Details	ACT_SITE: Proton acceptor

Chain	Residue	Details
A	TYR183
B	TYR183
C	TYR183
D	TYR183
E	TYR183
F	TYR183
G	TYR183
H	TYR183

site_id	SWS_FT_FI2
Number of Residues	40
Details	BINDING:

Chain	Residue	Details
A	GLY41
B	TYR183
C	GLY41
C	THR92
C	ASN119
C	SER170
C	TYR183
D	GLY41
D	THR92
D	ASN119
D	SER170
A	THR92
D	TYR183
E	GLY41
E	THR92
E	ASN119
E	SER170
E	TYR183
F	GLY41
F	THR92
F	ASN119
F	SER170
A	ASN119
F	TYR183
G	GLY41
G	THR92
G	ASN119
G	SER170
G	TYR183
H	GLY41
H	THR92
H	ASN119
H	SER170
A	SER170
H	TYR183
A	TYR183
B	GLY41
B	THR92
B	ASN119
B	SER170

site_id	SWS_FT_FI3
Number of Residues	8
Details	BINDING: BINDING => ECO:0000250\|UniProtKB:P28845

Chain	Residue	Details
A	ILE218
B	ILE218
C	ILE218
D	ILE218
E	ILE218
F	ILE218
G	ILE218
H	ILE218

site_id	SWS_FT_FI4
Number of Residues	16
Details	CARBOHYD: N-linked (GlcNAc...) asparagine => ECO:0000255

Chain	Residue	Details
A	ASN162
E	ASN207
F	ASN162
F	ASN207
G	ASN162
G	ASN207
H	ASN162
H	ASN207
A	ASN207
B	ASN162
B	ASN207
C	ASN162
C	ASN207
D	ASN162
D	ASN207
E	ASN162

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