Chlorine in PDB 7mbo: Factor Xia (Pichia Pastoris; C500S [C122S]) in Complex with the Inhibitor Milvexian (Bms-986177), Iupac Name:(6R,10S)-10-{4-[5- Chloro-2-(4-Chloro-1H-1,2,3-Triazol-1-Yl)Phenyl]-6- Oxopyrimidin- 1(6H)-Yl}-1-(Difluoromethyl)-6-Methyl-1,4,7,8,9,10-Hexahydro-15,11- (Metheno)Pyrazolo[4,3-B][1,7]Diazacyclotetradecin-5(6H)-One

Enzymatic activity of Factor Xia (Pichia Pastoris; C500S [C122S]) in Complex with the Inhibitor Milvexian (Bms-986177), Iupac Name:(6R,10S)-10-{4-[5- Chloro-2-(4-Chloro-1H-1,2,3-Triazol-1-Yl)Phenyl]-6- Oxopyrimidin- 1(6H)-Yl}-1-(Difluoromethyl)-6-Methyl-1,4,7,8,9,10-Hexahydro-15,11- (Metheno)Pyrazolo[4,3-B][1,7]Diazacyclotetradecin-5(6H)-One

All present enzymatic activity of Factor Xia (Pichia Pastoris; C500S [C122S]) in Complex with the Inhibitor Milvexian (Bms-986177), Iupac Name:(6R,10S)-10-{4-[5- Chloro-2-(4-Chloro-1H-1,2,3-Triazol-1-Yl)Phenyl]-6- Oxopyrimidin- 1(6H)-Yl}-1-(Difluoromethyl)-6-Methyl-1,4,7,8,9,10-Hexahydro-15,11- (Metheno)Pyrazolo[4,3-B][1,7]Diazacyclotetradecin-5(6H)-One:
3.4.21.27;

Protein crystallography data

The structure of Factor Xia (Pichia Pastoris; C500S [C122S]) in Complex with the Inhibitor Milvexian (Bms-986177), Iupac Name:(6R,10S)-10-{4-[5- Chloro-2-(4-Chloro-1H-1,2,3-Triazol-1-Yl)Phenyl]-6- Oxopyrimidin- 1(6H)-Yl}-1-(Difluoromethyl)-6-Methyl-1,4,7,8,9,10-Hexahydro-15,11- (Metheno)Pyrazolo[4,3-B][1,7]Diazacyclotetradecin-5(6H)-One, PDB code: 7mbo was solved by S.Sheriff, with X-Ray Crystallography technique. A brief refinement statistics is given in the table below:

Resolution Low / High (Å) 53.88 / 0.92
Space group P 21 21 21
Cell size a, b, c (Å), α, β, γ (°) 39.025, 69.588, 85.127, 90, 90, 90
R / Rfree (%) 16.2 / 16.8

Other elements in 7mbo:

The structure of Factor Xia (Pichia Pastoris; C500S [C122S]) in Complex with the Inhibitor Milvexian (Bms-986177), Iupac Name:(6R,10S)-10-{4-[5- Chloro-2-(4-Chloro-1H-1,2,3-Triazol-1-Yl)Phenyl]-6- Oxopyrimidin- 1(6H)-Yl}-1-(Difluoromethyl)-6-Methyl-1,4,7,8,9,10-Hexahydro-15,11- (Metheno)Pyrazolo[4,3-B][1,7]Diazacyclotetradecin-5(6H)-One also contains other interesting chemical elements:

Fluorine (F) 2 atoms

Chlorine Binding Sites:

The binding sites of Chlorine atom in the Factor Xia (Pichia Pastoris; C500S [C122S]) in Complex with the Inhibitor Milvexian (Bms-986177), Iupac Name:(6R,10S)-10-{4-[5- Chloro-2-(4-Chloro-1H-1,2,3-Triazol-1-Yl)Phenyl]-6- Oxopyrimidin- 1(6H)-Yl}-1-(Difluoromethyl)-6-Methyl-1,4,7,8,9,10-Hexahydro-15,11- (Metheno)Pyrazolo[4,3-B][1,7]Diazacyclotetradecin-5(6H)-One (pdb code 7mbo). This binding sites where shown within 5.0 Angstroms radius around Chlorine atom.
In total 2 binding sites of Chlorine where determined in the Factor Xia (Pichia Pastoris; C500S [C122S]) in Complex with the Inhibitor Milvexian (Bms-986177), Iupac Name:(6R,10S)-10-{4-[5- Chloro-2-(4-Chloro-1H-1,2,3-Triazol-1-Yl)Phenyl]-6- Oxopyrimidin- 1(6H)-Yl}-1-(Difluoromethyl)-6-Methyl-1,4,7,8,9,10-Hexahydro-15,11- (Metheno)Pyrazolo[4,3-B][1,7]Diazacyclotetradecin-5(6H)-One, PDB code: 7mbo:
Jump to Chlorine binding site number: 1; 2;

Chlorine binding site 1 out of 2 in 7mbo

Go back to Chlorine Binding Sites List in 7mbo
Chlorine binding site 1 out of 2 in the Factor Xia (Pichia Pastoris; C500S [C122S]) in Complex with the Inhibitor Milvexian (Bms-986177), Iupac Name:(6R,10S)-10-{4-[5- Chloro-2-(4-Chloro-1H-1,2,3-Triazol-1-Yl)Phenyl]-6- Oxopyrimidin- 1(6H)-Yl}-1-(Difluoromethyl)-6-Methyl-1,4,7,8,9,10-Hexahydro-15,11- (Metheno)Pyrazolo[4,3-B][1,7]Diazacyclotetradecin-5(6H)-One


Mono view


Stereo pair view

A full contact list of Chlorine with other atoms in the Cl binding site number 1 of Factor Xia (Pichia Pastoris; C500S [C122S]) in Complex with the Inhibitor Milvexian (Bms-986177), Iupac Name:(6R,10S)-10-{4-[5- Chloro-2-(4-Chloro-1H-1,2,3-Triazol-1-Yl)Phenyl]-6- Oxopyrimidin- 1(6H)-Yl}-1-(Difluoromethyl)-6-Methyl-1,4,7,8,9,10-Hexahydro-15,11- (Metheno)Pyrazolo[4,3-B][1,7]Diazacyclotetradecin-5(6H)-One within 5.0Å range:
probe atom residue distance (Å) B Occ
A:Cl302

b:7.6
occ:1.00
 CL1 A:YXG302 0.0 7.6 1.0
C15 A:YXG302 1.7 7.5 1.0
C7 A:YXG302 2.7 7.3 1.0
C4 A:YXG302 2.7 8.1 1.0
H45 A:YXG302 2.8 8.0 1.0
H48 A:YXG302 2.8 7.4 1.0
HA3 A:GLY226 3.0 7.9 1.0
HB3 A:ALA190 3.0 8.2 1.0
HG23 A:THR213 3.0 6.1 1.0
H A:VAL227 3.1 7.2 1.0
HA2 A:GLY226 3.4 7.9 1.0
H A:SER214 3.4 6.2 1.0
O A:TRP215 3.5 7.9 1.0
O A:VAL227 3.6 7.1 1.0
CA A:GLY226 3.6 7.9 1.0
N A:VAL227 3.6 7.2 1.0
H A:TRP215 3.6 7.2 1.0
CZ A:TYR228 3.7 7.5 1.0
HG22 A:THR213 3.8 6.1 1.0
HH A:TYR228 3.8 8.3 1.0
OH A:TYR228 3.8 8.2 1.0
CG2 A:THR213 3.8 6.1 1.0
CE1 A:TYR228 3.8 7.5 1.0
CB A:ALA190 3.9 8.2 1.0
C A:GLY226 3.9 7.4 1.0
HE1 A:TYR228 4.0 7.5 1.0
C3 A:YXG302 4.0 8.4 1.0
C12 A:YXG302 4.0 7.5 1.0
HA A:THR213 4.0 5.9 1.0
C A:TRP215 4.0 7.6 1.0
HB2 A:ALA190 4.0 8.2 1.0
N A:TRP215 4.0 7.2 1.0
N A:SER214 4.1 6.2 1.0
OD1 A:ASP189 4.1 13.6 1.0
CE2 A:TYR228 4.2 7.2 1.0
HB1 A:ALA190 4.2 8.3 1.0
C A:VAL227 4.2 7.0 1.0
H A:ALA190 4.4 8.7 1.0
CD1 A:TYR228 4.4 7.3 1.0
HG21 A:THR213 4.4 6.1 1.0
HE2 A:TYR228 4.5 7.2 1.0
C13 A:YXG302 4.5 8.2 1.0
CA A:TRP215 4.5 7.6 1.0
CA A:VAL227 4.5 7.3 1.0
O A:HOH431 4.6 13.4 1.0
HA A:TRP215 4.6 7.6 1.0
CA A:THR213 4.7 5.8 1.0
CD2 A:TYR228 4.7 6.8 1.0
HA3 A:GLY216 4.7 9.7 1.0
C A:SER214 4.7 6.9 1.0
H44 A:YXG302 4.7 8.4 1.0
CB A:THR213 4.8 5.9 1.0
C A:THR213 4.8 5.8 1.0
CG A:TYR228 4.8 7.1 1.0
N A:GLY216 4.8 8.3 1.0
HD1 A:TYR228 4.8 7.3 1.0
N A:GLY226 4.9 8.5 1.0
O A:GLY226 4.9 7.8 1.0
CA A:ALA190 5.0 8.1 1.0

Chlorine binding site 2 out of 2 in 7mbo

Go back to Chlorine Binding Sites List in 7mbo
Chlorine binding site 2 out of 2 in the Factor Xia (Pichia Pastoris; C500S [C122S]) in Complex with the Inhibitor Milvexian (Bms-986177), Iupac Name:(6R,10S)-10-{4-[5- Chloro-2-(4-Chloro-1H-1,2,3-Triazol-1-Yl)Phenyl]-6- Oxopyrimidin- 1(6H)-Yl}-1-(Difluoromethyl)-6-Methyl-1,4,7,8,9,10-Hexahydro-15,11- (Metheno)Pyrazolo[4,3-B][1,7]Diazacyclotetradecin-5(6H)-One


Mono view


Stereo pair view

A full contact list of Chlorine with other atoms in the Cl binding site number 2 of Factor Xia (Pichia Pastoris; C500S [C122S]) in Complex with the Inhibitor Milvexian (Bms-986177), Iupac Name:(6R,10S)-10-{4-[5- Chloro-2-(4-Chloro-1H-1,2,3-Triazol-1-Yl)Phenyl]-6- Oxopyrimidin- 1(6H)-Yl}-1-(Difluoromethyl)-6-Methyl-1,4,7,8,9,10-Hexahydro-15,11- (Metheno)Pyrazolo[4,3-B][1,7]Diazacyclotetradecin-5(6H)-One within 5.0Å range:
probe atom residue distance (Å) B Occ
A:Cl302

b:15.9
occ:1.00
 CL2 A:YXG302 0.0 15.9 1.0
C18 A:YXG302 1.7 11.3 1.0
N33 A:YXG302 2.7 11.0 1.0
C10 A:YXG302 2.8 10.2 1.0
HD11 A:LEU147 2.9 20.2 1.0
H51 A:YXG302 3.1 10.2 1.0
HA2 A:GLY218 3.2 12.5 1.0
O A:HOH562 3.3 18.1 1.0
HD12 A:LEU147 3.3 20.2 1.0
CD1 A:LEU147 3.4 20.2 1.0
HE3 A:LYS192 3.5 14.3 1.0
HD13 A:LEU147 3.5 20.2 1.0
H A:GLY218 3.5 12.3 1.0
O A:HOH613 3.8 21.0 1.0
N34 A:YXG302 3.8 9.9 1.0
N36 A:YXG302 3.8 8.9 1.0
CA A:GLY218 3.9 12.5 1.0
HE2 A:LYS192 3.9 14.3 1.0
N A:GLY218 4.1 12.3 1.0
CE A:LYS192 4.2 14.3 1.0
C A:GLY218 4.2 11.8 1.0
SG A:CYS219 4.4 13.3 1.0
HG3 A:LYS192 4.4 10.2 1.0
O A:GLY218 4.4 12.0 1.0
HG2 A:LYS192 4.6 10.2 1.0
HA3 A:GLY218 4.8 12.5 1.0
CG A:LEU147 4.9 19.7 1.0
N A:CYS219 4.9 12.4 1.0
HZ1 A:LYS192 4.9 16.1 1.0
CG A:LYS192 4.9 10.2 1.0

Reference:

A.K.Dilger, K.B.Pabbisetty, J.R.Corte, T.Fang, W.Yang, D.J.P.Pinto, Y.Wang, Y.Zhu, A.Mathur, J.Li, X.Hou, D.Smith, D.Sun, H.Zhang, S.Krishnananthan, D.R.Wu, J.E.Myers, S.Sheriff, K.A.Rossi, S.Chacko, J.J.Zheng, M.A.Galella, T.Ziemba, E.A.Dierks, J.M.Bozarth, Y.Wu, E.Crain, P.C.Wong, J.M.Luettgen, R.R.Wexler, W.R.Ewing. Discovery of Milvexian, A High-Affinity, Orally Bioavailable Inhibitor of Factor Xia in Clinical Studies For Antithrombotic Therapy Journal of Medicinal 2021CHEMISTRY.
DOI: 10.1021/ACS.JMEDCHEM.1C00613
Page generated: Tue Jul 30 00:27:28 2024

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