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Fluorine in PDB 5pgw: Crystal Structure of 11BETA-HSD1 Double Mutant (L262R, F278E) Complexed with 2-[(1R,3S,5R,7S)-2-[4-(4-Fluorophenyl)Phenyl]-6- Hydroxyadamantan-2-Yl]-1-(3- Hydroxyazetidin-1-Yl)Ethan-1-One

Enzymatic activity of Crystal Structure of 11BETA-HSD1 Double Mutant (L262R, F278E) Complexed with 2-[(1R,3S,5R,7S)-2-[4-(4-Fluorophenyl)Phenyl]-6- Hydroxyadamantan-2-Yl]-1-(3- Hydroxyazetidin-1-Yl)Ethan-1-One

All present enzymatic activity of Crystal Structure of 11BETA-HSD1 Double Mutant (L262R, F278E) Complexed with 2-[(1R,3S,5R,7S)-2-[4-(4-Fluorophenyl)Phenyl]-6- Hydroxyadamantan-2-Yl]-1-(3- Hydroxyazetidin-1-Yl)Ethan-1-One:
1.1.1.146;

Protein crystallography data

The structure of Crystal Structure of 11BETA-HSD1 Double Mutant (L262R, F278E) Complexed with 2-[(1R,3S,5R,7S)-2-[4-(4-Fluorophenyl)Phenyl]-6- Hydroxyadamantan-2-Yl]-1-(3- Hydroxyazetidin-1-Yl)Ethan-1-One, PDB code: 5pgw was solved by S.Sheriff, with X-Ray Crystallography technique. A brief refinement statistics is given in the table below:

Resolution Low / High (Å) 38.24 / 2.37
Space group P 21 21 21
Cell size a, b, c (Å), α, β, γ (°) 74.300, 92.800, 162.000, 90.00, 90.00, 90.00
R / Rfree (%) 21.7 / 23.8

Fluorine Binding Sites:

The binding sites of Fluorine atom in the Crystal Structure of 11BETA-HSD1 Double Mutant (L262R, F278E) Complexed with 2-[(1R,3S,5R,7S)-2-[4-(4-Fluorophenyl)Phenyl]-6- Hydroxyadamantan-2-Yl]-1-(3- Hydroxyazetidin-1-Yl)Ethan-1-One (pdb code 5pgw). This binding sites where shown within 5.0 Angstroms radius around Fluorine atom.
In total 4 binding sites of Fluorine where determined in the Crystal Structure of 11BETA-HSD1 Double Mutant (L262R, F278E) Complexed with 2-[(1R,3S,5R,7S)-2-[4-(4-Fluorophenyl)Phenyl]-6- Hydroxyadamantan-2-Yl]-1-(3- Hydroxyazetidin-1-Yl)Ethan-1-One, PDB code: 5pgw:
Jump to Fluorine binding site number: 1; 2; 3; 4;

Fluorine binding site 1 out of 4 in 5pgw

Go back to Fluorine Binding Sites List in 5pgw
Fluorine binding site 1 out of 4 in the Crystal Structure of 11BETA-HSD1 Double Mutant (L262R, F278E) Complexed with 2-[(1R,3S,5R,7S)-2-[4-(4-Fluorophenyl)Phenyl]-6- Hydroxyadamantan-2-Yl]-1-(3- Hydroxyazetidin-1-Yl)Ethan-1-One


Mono view


Stereo pair view

A full contact list of Fluorine with other atoms in the F binding site number 1 of Crystal Structure of 11BETA-HSD1 Double Mutant (L262R, F278E) Complexed with 2-[(1R,3S,5R,7S)-2-[4-(4-Fluorophenyl)Phenyl]-6- Hydroxyadamantan-2-Yl]-1-(3- Hydroxyazetidin-1-Yl)Ethan-1-One within 5.0Å range:
probe atom residue distance (Å) B Occ
A:F302

b:49.9
occ:1.00
 F31 A:8KA302 0.0 49.9 1.0
C28 A:8KA302 1.4 47.1 1.0
C29 A:8KA302 2.3 45.2 1.0
C27 A:8KA302 2.4 45.2 1.0
H60 A:8KA302 2.6 45.2 0.0
H59 A:8KA302 2.6 45.2 0.0
O B:SER283 3.4 81.7 1.0
C30 A:8KA302 3.6 43.3 1.0
C26 A:8KA302 3.6 44.0 1.0
CD A:PRO178 3.8 40.8 1.0
CD1 B:TYR280 3.9 68.2 1.0
CE A:MET179 4.0 50.4 1.0
CG A:PRO178 4.1 44.8 1.0
C25 A:8KA302 4.1 43.4 1.0
CE1 B:TYR280 4.2 69.1 1.0
CG B:TYR280 4.4 66.0 1.0
CD2 B:TYR284 4.4 88.1 1.0
CD2 A:TYR177 4.5 43.7 1.0
O B:TYR280 4.5 64.5 1.0
H61 A:8KA302 4.5 43.3 0.0
H58 A:8KA302 4.5 44.0 0.0
C B:SER283 4.5 82.1 1.0
OG B:SER283 4.6 88.2 1.0
CG B:TYR284 4.7 86.4 1.0
CB B:TYR284 4.8 82.9 1.0
CB B:TYR280 4.8 63.3 1.0
O A:PRO178 4.8 38.8 1.0
CZ B:TYR280 4.9 74.9 1.0
N A:PRO178 4.9 38.8 1.0
CB B:SER283 5.0 80.9 1.0

Fluorine binding site 2 out of 4 in 5pgw

Go back to Fluorine Binding Sites List in 5pgw
Fluorine binding site 2 out of 4 in the Crystal Structure of 11BETA-HSD1 Double Mutant (L262R, F278E) Complexed with 2-[(1R,3S,5R,7S)-2-[4-(4-Fluorophenyl)Phenyl]-6- Hydroxyadamantan-2-Yl]-1-(3- Hydroxyazetidin-1-Yl)Ethan-1-One


Mono view


Stereo pair view

A full contact list of Fluorine with other atoms in the F binding site number 2 of Crystal Structure of 11BETA-HSD1 Double Mutant (L262R, F278E) Complexed with 2-[(1R,3S,5R,7S)-2-[4-(4-Fluorophenyl)Phenyl]-6- Hydroxyadamantan-2-Yl]-1-(3- Hydroxyazetidin-1-Yl)Ethan-1-One within 5.0Å range:
probe atom residue distance (Å) B Occ
B:F302

b:30.1
occ:1.00
 F31 B:8KA302 0.0 30.1 1.0
C28 B:8KA302 1.4 28.2 1.0
C27 B:8KA302 2.4 28.3 1.0
C29 B:8KA302 2.4 22.4 1.0
H59 B:8KA302 2.6 28.3 0.0
H60 B:8KA302 2.6 22.3 0.0
CD1 A:TYR284 3.0 47.4 1.0
CE1 A:TYR284 3.2 47.9 1.0
O A:TYR280 3.2 49.5 1.0
C26 B:8KA302 3.6 25.2 1.0
C30 B:8KA302 3.6 22.5 1.0
CD B:PRO178 4.0 21.8 1.0
CG A:TYR284 4.0 46.2 1.0
C25 B:8KA302 4.1 22.7 1.0
C A:TYR280 4.2 48.5 1.0
CZ A:TYR284 4.2 54.8 1.0
CD2 B:TYR177 4.2 22.4 1.0
CG B:PRO178 4.2 26.0 1.0
CB A:TYR280 4.4 44.7 1.0
H58 B:8KA302 4.5 25.2 0.0
CE B:MET179 4.5 30.6 1.0
H61 B:8KA302 4.5 22.5 0.0
O A:HOH422 4.5 22.4 1.0
CB A:TYR284 4.7 45.5 1.0
CG2 B:VAL231 4.8 30.0 1.0
CE2 B:TYR177 4.8 22.8 1.0
CD2 A:TYR284 4.9 47.4 1.0
OH A:TYR284 4.9 54.8 1.0
CA A:TYR280 4.9 42.6 1.0
CE2 A:TYR284 4.9 48.4 1.0

Fluorine binding site 3 out of 4 in 5pgw

Go back to Fluorine Binding Sites List in 5pgw
Fluorine binding site 3 out of 4 in the Crystal Structure of 11BETA-HSD1 Double Mutant (L262R, F278E) Complexed with 2-[(1R,3S,5R,7S)-2-[4-(4-Fluorophenyl)Phenyl]-6- Hydroxyadamantan-2-Yl]-1-(3- Hydroxyazetidin-1-Yl)Ethan-1-One


Mono view


Stereo pair view

A full contact list of Fluorine with other atoms in the F binding site number 3 of Crystal Structure of 11BETA-HSD1 Double Mutant (L262R, F278E) Complexed with 2-[(1R,3S,5R,7S)-2-[4-(4-Fluorophenyl)Phenyl]-6- Hydroxyadamantan-2-Yl]-1-(3- Hydroxyazetidin-1-Yl)Ethan-1-One within 5.0Å range:
probe atom residue distance (Å) B Occ
D:F302

b:21.6
occ:1.00
 F31 D:8KA302 0.0 21.6 1.0
C28 D:8KA302 1.4 22.9 1.0
C29 D:8KA302 2.4 19.4 1.0
C27 D:8KA302 2.4 22.7 1.0
H60 D:8KA302 2.6 19.4 0.0
H59 D:8KA302 2.6 22.6 0.0
CB E:SER283 3.4 83.7 1.0
C30 D:8KA302 3.6 19.5 1.0
C26 D:8KA302 3.6 19.0 1.0
CE D:MET179 4.0 28.3 1.0
CD D:PRO178 4.1 18.4 1.0
C25 D:8KA302 4.1 18.0 1.0
CG2 D:VAL231 4.2 33.5 1.0
CG D:PRO178 4.2 22.8 1.0
O E:TYR280 4.2 72.6 1.0
H61 D:8KA302 4.5 19.5 0.0
H58 D:8KA302 4.5 19.0 0.0
CD2 D:TYR177 4.7 16.6 1.0
CA E:SER283 4.8 79.6 1.0

Fluorine binding site 4 out of 4 in 5pgw

Go back to Fluorine Binding Sites List in 5pgw
Fluorine binding site 4 out of 4 in the Crystal Structure of 11BETA-HSD1 Double Mutant (L262R, F278E) Complexed with 2-[(1R,3S,5R,7S)-2-[4-(4-Fluorophenyl)Phenyl]-6- Hydroxyadamantan-2-Yl]-1-(3- Hydroxyazetidin-1-Yl)Ethan-1-One


Mono view


Stereo pair view

A full contact list of Fluorine with other atoms in the F binding site number 4 of Crystal Structure of 11BETA-HSD1 Double Mutant (L262R, F278E) Complexed with 2-[(1R,3S,5R,7S)-2-[4-(4-Fluorophenyl)Phenyl]-6- Hydroxyadamantan-2-Yl]-1-(3- Hydroxyazetidin-1-Yl)Ethan-1-One within 5.0Å range:
probe atom residue distance (Å) B Occ
E:F302

b:43.5
occ:1.00
 F31 E:8KA302 0.0 43.5 1.0
C28 E:8KA302 1.4 40.3 1.0
C27 E:8KA302 2.3 38.7 1.0
C29 E:8KA302 2.3 36.0 1.0
H60 E:8KA302 2.6 36.0 0.0
H59 E:8KA302 2.6 38.7 0.0
C26 E:8KA302 3.6 37.0 1.0
C30 E:8KA302 3.6 33.3 1.0
CB D:TYR284 3.8 85.7 1.0
CG2 E:VAL231 3.9 53.8 1.0
CG E:PRO178 3.9 20.4 1.0
CD E:PRO178 3.9 16.7 1.0
C25 E:8KA302 4.1 35.0 1.0
CE E:MET179 4.2 33.0 1.0
O D:TYR280 4.3 57.2 1.0
H58 E:8KA302 4.5 37.1 0.0
H61 E:8KA302 4.5 33.2 0.0
N D:TYR284 4.6 62.1 1.0
CD2 E:TYR177 4.7 24.7 1.0
CB D:SER283 4.7 64.9 1.0
CA D:TYR284 4.8 84.5 1.0
CG1 E:VAL231 4.9 53.7 1.0
O E:PRO178 4.9 19.2 1.0

Reference:

X.Y.Ye, S.Y.Chen, S.Wu, D.S.Yoon, H.Wang, Z.Hong, S.P.O'connor, J.Li, J.J.Li, L.J.Kennedy, S.J.Walker, A.Nayeem, S.Sheriff, D.M.Camac, V.Ramamurthy, P.E.Morin, R.Zebo, J.R.Taylor, N.N.Morgan, R.P.Ponticiello, T.Harrity, A.Apedo, R.Golla, R.Seethala, M.Wang, T.W.Harper, B.G.Sleczka, B.He, M.Kirby, D.K.Leahy, J.Li, R.L.Hanson, Z.Guo, Y.X.Li, J.D.Dimarco, R.Scaringe, B.Maxwell, F.Moulin, J.C.Barrish, D.A.Gordon, J.A.Robl. Discovery of Clinical Candidate 2-((2S,6S)-2-Phenyl-6-Hydroxyadamantan-2-Yl) -1-(3'-Hydroxyazetidin-1-Yl)Ethanone [Bms-816336], An Orally Active Novel Selective 11 Beta-Hydroxysteroid Dehydrogenase Type 1 Inhibitor. J. Med. Chem. V. 60 4932 2017.
ISSN: ISSN 1520-4804
PubMed: 28537398
DOI: 10.1021/ACS.JMEDCHEM.7B00211
Page generated: Thu Aug 1 12:46:27 2024

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