DP00023: Estradiol 17-beta-dehydrogenase 1FASTA viewXML view

General information
DisProt:DP00023
Name:Estradiol 17-beta-dehydrogenase 1
Synonym(s):DHB1_HUMAN
17-beta-hydroxysteroid dehydrogenase type 1
17-beta-HSD 1
Placental 17-beta-hydroxysteroid dehydrogenase
20 alpha-hydroxysteroid dehydrogenase
20-alpha-HSD
E2DH
EC=1.1.1.62
First appeared in release:Release 3.0 (02/17/2006)
UniProt:P14061
UniGene:Hs.654385
SwissProt: DHB1_HUMAN
TrEMBL:  
NCBI (GI): 118554
Source organism:Homo sapiens (Human)
Sequence length:327
Percent disordered:19%
Homologues: 


Native sequence

        10         20         30         40         50         60
         |          |          |          |          |          |
ARTVVLITGC SSGIGLHLAV RLASDPSQSF KVYATLRDLK TQGRLWEAAR ALACPPGSLE - 60
TLQLDVRDSK SVAAARERVT EGRVDVLVCN AGLGLLGPLE ALGEDAVASV LDVNVVGTVR - 120
MLQAFLPDMK RRGSGRVLVT GSVGGLMGLP FNDVYCASKF ALEGLCESLA VLLLPFGVHL - 180
SLIECGPVHT AFMEKVLGSP EEVLDRTDIH TFHRFYQYLA HSKQVFREAA QNPEEVAEVF - 240
LTALRAPKPT LRYFTTERFL PLLRMRLDDP SGSNYVTAMH REVFGDVPAK AEAGAEAGGG - 300
AGPGAEDEAG RSAVGDPELG DPPAAPQ



Functional narrative    

Human estrogenic 17-beta-hydroxysteroid dehydrogenase 1 (17-beta-HSD 1) mediates the reversible interconvertion of the biologically inactive estrone (E1), to the active estrogen E2, and thus plays a crucial role in the regulation of intracellular levels of active estrogens in a variety of normal and cancerous tissues. 17-beta-HSD 1 functions as a homodimer.

Region 3: 191-195 Region 9: 192-195 Region 8: 190-197 Region 19: 191-197 Region 15: 192-197 Region 13: 191-198 Region 4: 192-198 Region 14: 191-200 Region 17: 190-201 Region 12: 198-201 Region 11: 198-202 Region 10: 199-202 Region 2: 190-207 Region 18: 192-207 Region 16: 286-289 Region 1: 285-327 Region 5: 286-327 Region 6: 288-327 Region 7: 289-327

Map of ordered and disordered regions







Note: 'Mouse' over a region to see the start and stop residues. Click on a region to see detailed information.


Region 1
Type:Disordered - Extended
Name: 
Location:285 - 327
Length:43
Region sequence:

GDVPAKAEAGAEAGGGAGPGAEDEAGRSAVGDPELGDPPAAPQ

Modification type: Native
PDB: 1BHS:_, 1DHT:A, 1EQU:A, 1EQU:B, 1IOL:_, 3DHE:A
Structural/functional type: Relationship to function unknown
Functional classes: Unknown
Functional subclasses: Unknown
Detection methods:
  1. X-ray crystallography

  2. Mass spectrometry-based high resolution hydrogen-deuterium exchange
References:
  1. Azzi A, Rehse PH, Zhu DW, Campbell RL, Labrie F, Lin SX. "Crystal structure of human estrogenic 17 beta-hydroxysteroid dehydrogenase complexed with 17 beta-estradiol." Nat Struct Biol. 1996; 3(8): 665-8. PubMed: 8756321

  2. Ghosh D, Pletnev VZ, Zhu DW, Wawrzak Z, Duax WL, Pangborn W, Labrie F, Lin SX. "Structure of human estrogenic 17 beta-hydroxysteroid dehydrogenase at 2.20 A resolution." Structure. 1995; 3(5): 503-513. PubMed: 7663947

  3. Han Q, Campbell RL, Gangloff A, Huang YW, Lin SX. "Dehydroepiandrosterone and dihydrotestosterone recognition by human estrogenic 17beta-hydroxysteroid dehydrogenase. C-18/c-19 steroid discrimination and enzyme-induced strain." J Biol Chem. 2000; 275(2): 1105-1111. PubMed: 10625652

  4. Sawicki MW, Erman M, Puranen T, Vihko P, Ghosh D. "Structure of the ternary complex of human 17beta-hydroxysteroid dehydrogenase type 1 with 3-hydroxyestra-1,3,5,7-tetraen-17-one (equilin) and NADP+." Proc Natl Acad Sci U S A. 1999; 96(3): 840-845. PubMed: 9927655
Comments:
The 3DHE:A PDB file gives this protein fragment as complexed with Dehydroepiandrosterone.

The 1DHT:A PDB file gives this protein fragment as complexed with Dihydrotestosterone.

The 1EQU:A and B PDB files, give this protein fragment as complexed with NADP+ and 3-hydroxyestra-1,3,5,7-tetraen-17-one, (equilin).

The 1IOL PDB file gives this protein fragment as complexed with Estradiol.

The 1BHS PDB file gives the amino acid sequence for the uncomplexed, unmutated crystal structure of this protein.




Region 2
Type:Disordered - Extended
Name: 
Location:190 - 207
Length:18
Region sequence:

TAFMEKVLGSPEEVLDRT

Modification type: Complex
Native
PDB: 1IOL:_
Structural/functional type: Relationship to function unknown
Functional classes: Unknown
Molecular recognition effectors
Functional subclasses: Substrate/ligand binding
Detection methods:
  1. X-ray crystallography
References:
  1. Azzi A, Rehse PH, Zhu DW, Campbell RL, Labrie F, Lin SX. "Crystal structure of human estrogenic 17 beta-hydroxysteroid dehydrogenase complexed with 17 beta-estradiol." Nat Struct Biol. 1996; 3(8): 665-8. PubMed: 8756321
Comments:
The 1IOL PDB file gives this protein fragment as complexed with Estradiol.


Region 3
Type:Disordered - Extended
Name: 
Location:191 - 195
Length:5
Region sequence:

AFMEK

Modification type: Complex
PDB: 1FDS:_, 1FDT:_
Structural/functional type: Function arises from the disordered state
Functional classes: Molecular recognition effectors
Functional subclasses: Disordered region is not essential for protein function
Substrate/ligand binding
Detection methods:
  1. X-ray crystallography

  2. Mass spectrometry-based high resolution hydrogen-deuterium exchange
References:
  1. Breton R, Housset D, Mazza C, Fontecilla-Camps JC. "The structure of a complex of human 17beta-hydroxysteroid dehydrogenase with estradiol and NADP+ identifies two principal targets for the design of inhibitors." Structure. 1996; 4(8): 905-15. PubMed: 8805577
Comments:
The 1FDT PDB gives this protein fragment as complexed with 17-Beta-Estradiol and NADP+ at low temperature, 123 K.

The 1FDS PDB file gives this protein fragment as complexed with 17-Beta-Estradiol at room temperature.


Region 4
Type:Disordered - Extended
Name: 
Location:192 - 198
Length:7
Region sequence:

FMEKVLG

Modification type: Complex
PDB: 1FDS:_, 1FDT:_
Structural/functional type: Function arises from the disordered state
Functional classes: Molecular recognition effectors
Functional subclasses: Disordered region is not essential for protein function
Substrate/ligand binding
Detection methods:
  1. X-ray crystallography

  2. Mass spectrometry-based high resolution hydrogen-deuterium exchange
References:
  1. Breton R, Housset D, Mazza C, Fontecilla-Camps JC. "The structure of a complex of human 17beta-hydroxysteroid dehydrogenase with estradiol and NADP+ identifies two principal targets for the design of inhibitors." Structure. 1996; 4(8): 905-15. PubMed: 8805577
Comments:
The 1FDT PDB gives this protein fragment as complexed with 17-Beta-Estradiol and NADP+ at low temperature, 123 K.

The 1FDS PDB file gives this protein fragment as complexed with 17-Beta-Estradiol at room temperature.


Region 5
Type:Disordered - Extended
Name: 
Location:286 - 327
Length:42
Region sequence:

DVPAKAEAGAEAGGGAGPGAEDEAGRSAVGDPELGDPPAAPQ

Modification type: Complex
PDB: 1FDS:_, 1FDT:_, 1FDU:A, 1FDU:B, 1FDU:C, 1FDU:D, 1FDV:A, 1FDV:B, 1FDV:C, 1FDV:D, 1FDW:_, 1I5R:A, 1JTV:A
Structural/functional type: Relationship to function unknown
Functional classes: Unknown
Functional subclasses: Disordered region is not essential for protein function
Protein-lipid interaction
Detection methods:
  1. Fourier transform infrared spectroscopy (FTIR), aka infrared spectroscopy)

  2. Mass spectrometry-based high resolution hydrogen-deuterium exchange

  3. Nuclear magnetic resonance (NMR)

  4. X-ray crystallography
References:
  1. Breton R, Housset D, Mazza C, Fontecilla-Camps JC. "The structure of a complex of human 17beta-hydroxysteroid dehydrogenase with estradiol and NADP+ identifies two principal targets for the design of inhibitors." Structure. 1996; 4(8): 905-15. PubMed: 8805577

  2. Gangloff A, Shi R, Nahoum V, Lin SX. "Pseudo-symmetry of C19 steroids, alternative binding orientations, and multispecificity in human estrogenic 17beta-hydroxysteroid dehydrogenase." Faseb J. 2003; 17(2): 274-276. PubMed: 12490543

  3. Mazza C, Breton R, Housset D, Fontecilla-Camps JC. "Unusual charge stabilization of NADP+ in 17beta-hydroxysteroid dehydrogenase." J Biol Chem. 1998; 273(14): 8145-8152. PubMed: 9525918

  4. Qiu W, Campbell RL, Gangloff A, Dupuis P, Boivin RP, Tremblay MR, Poirier D, Lin SX. "A concerted, rational design of type 1 17beta-hydroxysteroid dehydrogenase inhibitors: estradiol-adenosine hybrids with high affinity." Faseb J. 2002; 16(13): 1829-1831. PubMed: 12223444
Comments:
The 1I5R:A PDB file gives this protein as complexed with an 8-methylene-based inhibitor- an EM-1745 complex.

The 1JTV:A PDB file gives this protein fragment as complexed with testosterone.

The 1FDW PDB file gives this protein fragment as complexed with Estradiol and has the mutation H221Q.

The 1FDV PDB file gives this protein fragment as complexed with NAD+ and has the mutation H221L.

The 1FDU PDB file gives this protein fragment as complexed with Estradiol and NADP+ and has the mutation H221L.

The 1FDT PDB file gives this protein fragment as complexed with 17-Beta-Estradiol and NADP+ at low temperature, 123 K.

The 1FDS PDB file gives this protein fragment as complexed with 17-Beta-Estradiol at room temperature.

The experimental sequence used for the PDB ID 1FDU contained a H221L substitution.

The experimental sequence used for PDB ID 1FDV contained a H221L substitution.


Region 6
Type:Disordered - Extended
Name: 
Location:288 - 327
Length:40
Region sequence:

PAKAEAGAEAGGGAGPGAEDEAGRSAVGDPELGDPPAAPQ

Modification type: Complex
PDB: 1FDS:_, 1FDT:_
Structural/functional type: Relationship to function unknown
Functional classes: Unknown
Functional subclasses: Disordered region is not essential for protein function
Protein-lipid interaction
Detection methods:
  1. X-ray crystallography

  2. Mass spectrometry-based high resolution hydrogen-deuterium exchange
References:
  1. Breton R, Housset D, Mazza C, Fontecilla-Camps JC. "The structure of a complex of human 17beta-hydroxysteroid dehydrogenase with estradiol and NADP+ identifies two principal targets for the design of inhibitors." Structure. 1996; 4(8): 905-15. PubMed: 8805577
Comments:
The 1FDT PDB gives this protein fragment as complexed with 17-Beta-Estradiol and NADP+ at low temperature, 123 K.

The 1FDS PDB file gives this protein fragment as complexed with 17-Beta-Estradiol at room temperature.




Region 7
Type:Disordered - Extended
Name: 
Location:289 - 327
Length:39
Region sequence:

AKAEAGAEAGGGAGPGAEDEAGRSAVGDPELGDPPAAPQ

Modification type: Complex
PDB: 1FDS:_, 1FDT:_
Structural/functional type: Relationship to function unknown
Functional classes: Unknown
Functional subclasses: Disordered region is not essential for protein function
Protein-lipid interaction
Detection methods:
  1. X-ray crystallography

  2. Mass spectrometry-based high resolution hydrogen-deuterium exchange
References:
  1. Breton R, Housset D, Mazza C, Fontecilla-Camps JC. "The structure of a complex of human 17beta-hydroxysteroid dehydrogenase with estradiol and NADP+ identifies two principal targets for the design of inhibitors." Structure. 1996; 4(8): 905-15. PubMed: 8805577
Comments:
The 1FDT PDB gives this protein fragment as complexed with 17-Beta-Estradiol and NADP+ at low temperature, 123 K.

The 1FDS PDB file gives this protein fragment as complexed with 17-Beta-Estradiol at room temperature.




Region 8
Type:Disordered
Name: 
Location:190 - 197
Length:8
Region sequence:

TAFMEKVL

Modification type: Complex
PDB: 1FDT:_
Structural/functional type: Function arises from the disordered state
Functional classes: Molecular recognition effectors
Functional subclasses: Substrate/ligand binding
Detection methods:
  1. X-ray crystallography (123 K; )

  2. Mass spectrometry-based high resolution hydrogen-deuterium exchange
References:
  1. Breton R, Housset D, Mazza C, Fontecilla-Camps JC. "The structure of a complex of human 17beta-hydroxysteroid dehydrogenase with estradiol and NADP+ identifies two principal targets for the design of inhibitors." Structure. 1996; 4(8): 905-15. PubMed: 8805577
Comments:
The 1FDT PDB gives this protein fragment as complexed with 17-Beta-Estradiol and NADP+ at low temperature, 123 K.




Region 9
Type:Disordered
Name: 
Location:192 - 195
Length:4
Region sequence:

FMEK

Modification type: Complex
PDB: 1FDT:_
Structural/functional type: Function arises from the disordered state
Functional classes: Molecular recognition effectors
Functional subclasses: Substrate/ligand binding
Detection methods:
  1. X-ray crystallography (123 K; )

  2. Mass spectrometry-based high resolution hydrogen-deuterium exchange
References:
  1. Breton R, Housset D, Mazza C, Fontecilla-Camps JC. "The structure of a complex of human 17beta-hydroxysteroid dehydrogenase with estradiol and NADP+ identifies two principal targets for the design of inhibitors." Structure. 1996; 4(8): 905-15. PubMed: 8805577
Comments:
The 1FDT PDB gives this protein fragment as complexed with 17-Beta-Estradiol and NADP+ at low temperature, 123 K.




Region 10
Type:Disordered - Extended
Name: 
Location:199 - 202
Length:4
Region sequence:

SPEE

Modification type: Complex
Engineered
PDB: 1FDU:A
Structural/functional type: Function arises from the disordered state
Functional classes: Molecular recognition effectors
Functional subclasses: Disordered region is not essential for protein function
Substrate/ligand binding
Detection methods:
  1. X-ray crystallography
References:
  1. Mazza C, Breton R, Housset D, Fontecilla-Camps JC. "Unusual charge stabilization of NADP+ in 17beta-hydroxysteroid dehydrogenase." J Biol Chem. 1998; 273(14): 8145-8152. PubMed: 9525918
Comments:
The experimental sequence used for the PDB ID 1FDU contained a H221L substitution.




Region 11
Type:Disordered - Extended
Name: 
Location:198 - 202
Length:5
Region sequence:

GSPEE

Modification type: Complex
Engineered
PDB: 1FDU:B
Structural/functional type: Function arises from the disordered state
Functional classes: Molecular recognition effectors
Functional subclasses: Substrate/ligand binding
Detection methods:
  1. X-ray crystallography
References:
  1. Mazza C, Breton R, Housset D, Fontecilla-Camps JC. "Unusual charge stabilization of NADP+ in 17beta-hydroxysteroid dehydrogenase." J Biol Chem. 1998; 273(14): 8145-8152. PubMed: 9525918
Comments:
The experimental sequence included a H221L substitution.




Region 12
Type:Disordered - Extended
Name: 
Location:198 - 201
Length:4
Region sequence:

GSPE

Modification type: Complex
Engineered
PDB: 1FDU:D
Structural/functional type: Function arises from the disordered state
Functional classes: Molecular recognition effectors
Functional subclasses: Substrate/ligand binding
Detection methods:
  1. X-ray crystallography
References:
  1. Mazza C, Breton R, Housset D, Fontecilla-Camps JC. "Unusual charge stabilization of NADP+ in 17beta-hydroxysteroid dehydrogenase." J Biol Chem. 1998; 273(14): 8145-8152. PubMed: 9525918
Comments:
The experimental sequence included a H221L substitution.




Region 13
Type:Disordered - Extended
Name: 
Location:191 - 198
Length:8
Region sequence:

AFMEKVLG

Modification type: Complex
Engineered
PDB: 1FDV:A, 1FDV:B, 1FDV:C, 1FDV:D
Structural/functional type: Function arises from the disordered state
Functional classes: Molecular recognition effectors
Functional subclasses: Substrate/ligand binding
Detection methods:
  1. X-ray crystallography

  2. Mass spectrometry-based high resolution hydrogen-deuterium exchange
References:
  1. Mazza C, Breton R, Housset D, Fontecilla-Camps JC. "Unusual charge stabilization of NADP+ in 17beta-hydroxysteroid dehydrogenase." J Biol Chem. 1998; 273(14): 8145-8152. PubMed: 9525918
Comments:
The experimental sequence used for PDB ID 1FDV contained a H221L substitution.


Region 14
Type:Disordered - Extended
Name: 
Location:191 - 200
Length:10
Region sequence:

AFMEKVLGSP

Modification type: Complex
Engineered
PDB: 1FDV:A, 1FDV:B, 1FDV:C, 1FDV:D
Structural/functional type: Relationship to function unknown
Functional classes: Molecular recognition effectors
Functional subclasses: Substrate/ligand binding
Detection methods:
  1. X-ray crystallography

  2. Mass spectrometry-based high resolution hydrogen-deuterium exchange
References:
  1. Mazza C, Breton R, Housset D, Fontecilla-Camps JC. "Unusual charge stabilization of NADP+ in 17beta-hydroxysteroid dehydrogenase." J Biol Chem. 1998; 273(14): 8145-8152. PubMed: 9525918
Comments:
The experimental sequence used for PDB ID 1FDV contained a H221L substitution.


Region 15
Type:Disordered - Extended
Name: 
Location:192 - 197
Length:6
Region sequence:

FMEKVL

Modification type: Complex
Engineered
PDB: 1FDW:_
Structural/functional type: Function arises from the disordered state
Functional classes: Molecular recognition effectors
Functional subclasses: Disordered region is not essential for protein function
Substrate/ligand binding
Detection methods:
  1. X-ray crystallography
References:
  1. Mazza C, Breton R, Housset D, Fontecilla-Camps JC. "Unusual charge stabilization of NADP+ in 17beta-hydroxysteroid dehydrogenase." J Biol Chem. 1998; 273(14): 8145-8152. PubMed: 9525918
Comments:
The sequence used for PDB ID 1FDW contained a H221Q substitution.


Region 16
Type:Disordered
Name: 
Location:286 - 289
Length:4
Region sequence:

DVPA

Modification type: Complex
Engineered
Fragment
PDB: 1A27:_
Structural/functional type: Relationship to function unknown
Functional classes: Unknown
Functional subclasses: Disordered region is not essential for protein function
Protein-lipid interaction
Detection methods:
  1. X-ray crystallography
References:
  1. Mazza C, Breton R, Housset D, Fontecilla-Camps JC. "Unusual charge stabilization of NADP+ in 17beta-hydroxysteroid dehydrogenase." J Biol Chem. 1998; 273(14): 8145-8152. PubMed: 9525918
Comments:
The 1A27 PDB file gives this protein fragment as complexed with Estradiol and NADP+. It also has a C-terminal deletion mutation.




Region 17
Type:Disordered
Name: 
Location:190 - 201
Length:12
Region sequence:

TAFMEKVLGSPE

Modification type: Complex
PDB: 1EQU:A, 1EQU:B
Structural/functional type: Function arises from the disordered state
Functional classes: Molecular recognition effectors
Functional subclasses: Substrate/ligand binding
Detection methods:
  1. X-ray crystallography
References:
  1. Sawicki MW, Erman M, Puranen T, Vihko P, Ghosh D. "Structure of the ternary complex of human 17beta-hydroxysteroid dehydrogenase type 1 with 3-hydroxyestra-1,3,5,7-tetraen-17-one (equilin) and NADP+." Proc Natl Acad Sci U S A. 1999; 96(3): 840-845. PubMed: 9927655
Comments:
 



Region 18
Type:Disordered - Extended
Name: 
Location:192 - 207
Length:16
Region sequence:

FMEKVLGSPEEVLDRT

Modification type: Complex
Native
PDB: 1DHT:A, 3DHE:A
Structural/functional type: Relationship to function unknown
Functional classes: Molecular recognition effectors
Functional subclasses: Disordered region is not essential for protein function
Substrate/ligand binding
Detection methods:
  1. X-ray crystallography
References:
  1. Han Q, Campbell RL, Gangloff A, Huang YW, Lin SX. "Dehydroepiandrosterone and dihydrotestosterone recognition by human estrogenic 17beta-hydroxysteroid dehydrogenase. C-18/c-19 steroid discrimination and enzyme-induced strain." J Biol Chem. 2000; 275(2): 1105-1111. PubMed: 10625652
Comments:
The 3DHE PDB file gives this protein fragment as complexed with Dehydroepiandrosterone.

The 1DHT PDB file gives this protein fragment as complexed with Dihydrotestosterone.


Region 19
Type:Disordered
Name: 
Location:191 - 197
Length:7
Region sequence:

AFMEKVL

Modification type: Complex
PDB: 1JTV:A
Structural/functional type: Function arises from the disordered state
Functional classes: Molecular recognition effectors
Functional subclasses: Substrate/ligand binding
Detection methods:
  1. X-ray crystallography
References:
  1. Gangloff A, Shi R, Nahoum V, Lin SX. "Pseudo-symmetry of C19 steroids, alternative binding orientations, and multispecificity in human estrogenic 17beta-hydroxysteroid dehydrogenase." Faseb J. 2003; 17(2): 274-276. PubMed: 12490543
Comments:
The 1JTV PDB file gives this protein fragment as complexed with testosterone.




Comments


UniGene, Hs.655222


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