4XYC

NANOMOLAR INHIBITORS OF MYCOBACTERIUM TUBERCULOSIS GLUTAMINE SYNTHETASE 1: SYNTHESIS, BIOLOGICAL EVALUATION AND X-RAY CRYSTALLOGRAPHIC STUDIES

Functional Information from GO Data

Chain	GOid	namespace	contents
A	0000166	molecular_function	nucleotide binding
A	0003824	molecular_function	catalytic activity
A	0004356	molecular_function	glutamine synthetase activity
A	0005524	molecular_function	ATP binding
A	0005737	cellular_component	cytoplasm
A	0006542	biological_process	glutamine biosynthetic process
A	0016020	cellular_component	membrane
A	0016874	molecular_function	ligase activity
A	0019740	biological_process	nitrogen utilization
A	0046872	molecular_function	metal ion binding
B	0000166	molecular_function	nucleotide binding
B	0003824	molecular_function	catalytic activity
B	0004356	molecular_function	glutamine synthetase activity
B	0005524	molecular_function	ATP binding
B	0005737	cellular_component	cytoplasm
B	0006542	biological_process	glutamine biosynthetic process
B	0016020	cellular_component	membrane
B	0016874	molecular_function	ligase activity
B	0019740	biological_process	nitrogen utilization
B	0046872	molecular_function	metal ion binding
C	0000166	molecular_function	nucleotide binding
C	0003824	molecular_function	catalytic activity
C	0004356	molecular_function	glutamine synthetase activity
C	0005524	molecular_function	ATP binding
C	0005737	cellular_component	cytoplasm
C	0006542	biological_process	glutamine biosynthetic process
C	0016020	cellular_component	membrane
C	0016874	molecular_function	ligase activity
C	0019740	biological_process	nitrogen utilization
C	0046872	molecular_function	metal ion binding
D	0000166	molecular_function	nucleotide binding
D	0003824	molecular_function	catalytic activity
D	0004356	molecular_function	glutamine synthetase activity
D	0005524	molecular_function	ATP binding
D	0005737	cellular_component	cytoplasm
D	0006542	biological_process	glutamine biosynthetic process
D	0016020	cellular_component	membrane
D	0016874	molecular_function	ligase activity
D	0019740	biological_process	nitrogen utilization
D	0046872	molecular_function	metal ion binding
E	0000166	molecular_function	nucleotide binding
E	0003824	molecular_function	catalytic activity
E	0004356	molecular_function	glutamine synthetase activity
E	0005524	molecular_function	ATP binding
E	0005737	cellular_component	cytoplasm
E	0006542	biological_process	glutamine biosynthetic process
E	0016020	cellular_component	membrane
E	0016874	molecular_function	ligase activity
E	0019740	biological_process	nitrogen utilization
E	0046872	molecular_function	metal ion binding
F	0000166	molecular_function	nucleotide binding
F	0003824	molecular_function	catalytic activity
F	0004356	molecular_function	glutamine synthetase activity
F	0005524	molecular_function	ATP binding
F	0005737	cellular_component	cytoplasm
F	0006542	biological_process	glutamine biosynthetic process
F	0016020	cellular_component	membrane
F	0016874	molecular_function	ligase activity
F	0019740	biological_process	nitrogen utilization
F	0046872	molecular_function	metal ion binding
G	0000166	molecular_function	nucleotide binding
G	0003824	molecular_function	catalytic activity
G	0004356	molecular_function	glutamine synthetase activity
G	0005524	molecular_function	ATP binding
G	0005737	cellular_component	cytoplasm
G	0006542	biological_process	glutamine biosynthetic process
G	0016020	cellular_component	membrane
G	0016874	molecular_function	ligase activity
G	0019740	biological_process	nitrogen utilization
G	0046872	molecular_function	metal ion binding
H	0000166	molecular_function	nucleotide binding
H	0003824	molecular_function	catalytic activity
H	0004356	molecular_function	glutamine synthetase activity
H	0005524	molecular_function	ATP binding
H	0005737	cellular_component	cytoplasm
H	0006542	biological_process	glutamine biosynthetic process
H	0016020	cellular_component	membrane
H	0016874	molecular_function	ligase activity
H	0019740	biological_process	nitrogen utilization
H	0046872	molecular_function	metal ion binding
I	0000166	molecular_function	nucleotide binding
I	0003824	molecular_function	catalytic activity
I	0004356	molecular_function	glutamine synthetase activity
I	0005524	molecular_function	ATP binding
I	0005737	cellular_component	cytoplasm
I	0006542	biological_process	glutamine biosynthetic process
I	0016020	cellular_component	membrane
I	0016874	molecular_function	ligase activity
I	0019740	biological_process	nitrogen utilization
I	0046872	molecular_function	metal ion binding
J	0000166	molecular_function	nucleotide binding
J	0003824	molecular_function	catalytic activity
J	0004356	molecular_function	glutamine synthetase activity
J	0005524	molecular_function	ATP binding
J	0005737	cellular_component	cytoplasm
J	0006542	biological_process	glutamine biosynthetic process
J	0016020	cellular_component	membrane
J	0016874	molecular_function	ligase activity
J	0019740	biological_process	nitrogen utilization
J	0046872	molecular_function	metal ion binding
K	0000166	molecular_function	nucleotide binding
K	0003824	molecular_function	catalytic activity
K	0004356	molecular_function	glutamine synthetase activity
K	0005524	molecular_function	ATP binding
K	0005737	cellular_component	cytoplasm
K	0006542	biological_process	glutamine biosynthetic process
K	0016020	cellular_component	membrane
K	0016874	molecular_function	ligase activity
K	0019740	biological_process	nitrogen utilization
K	0046872	molecular_function	metal ion binding
L	0000166	molecular_function	nucleotide binding
L	0003824	molecular_function	catalytic activity
L	0004356	molecular_function	glutamine synthetase activity
L	0005524	molecular_function	ATP binding
L	0005737	cellular_component	cytoplasm
L	0006542	biological_process	glutamine biosynthetic process
L	0016020	cellular_component	membrane
L	0016874	molecular_function	ligase activity
L	0019740	biological_process	nitrogen utilization
L	0046872	molecular_function	metal ion binding
M	0000166	molecular_function	nucleotide binding
M	0003824	molecular_function	catalytic activity
M	0004356	molecular_function	glutamine synthetase activity
M	0005524	molecular_function	ATP binding
M	0005737	cellular_component	cytoplasm
M	0006542	biological_process	glutamine biosynthetic process
M	0016020	cellular_component	membrane
M	0016874	molecular_function	ligase activity
M	0019740	biological_process	nitrogen utilization
M	0046872	molecular_function	metal ion binding
N	0000166	molecular_function	nucleotide binding
N	0003824	molecular_function	catalytic activity
N	0004356	molecular_function	glutamine synthetase activity
N	0005524	molecular_function	ATP binding
N	0005737	cellular_component	cytoplasm
N	0006542	biological_process	glutamine biosynthetic process
N	0016020	cellular_component	membrane
N	0016874	molecular_function	ligase activity
N	0019740	biological_process	nitrogen utilization
N	0046872	molecular_function	metal ion binding
O	0000166	molecular_function	nucleotide binding
O	0003824	molecular_function	catalytic activity
O	0004356	molecular_function	glutamine synthetase activity
O	0005524	molecular_function	ATP binding
O	0005737	cellular_component	cytoplasm
O	0006542	biological_process	glutamine biosynthetic process
O	0016020	cellular_component	membrane
O	0016874	molecular_function	ligase activity
O	0019740	biological_process	nitrogen utilization
O	0046872	molecular_function	metal ion binding
P	0000166	molecular_function	nucleotide binding
P	0003824	molecular_function	catalytic activity
P	0004356	molecular_function	glutamine synthetase activity
P	0005524	molecular_function	ATP binding
P	0005737	cellular_component	cytoplasm
P	0006542	biological_process	glutamine biosynthetic process
P	0016020	cellular_component	membrane
P	0016874	molecular_function	ligase activity
P	0019740	biological_process	nitrogen utilization
P	0046872	molecular_function	metal ion binding
Q	0000166	molecular_function	nucleotide binding
Q	0003824	molecular_function	catalytic activity
Q	0004356	molecular_function	glutamine synthetase activity
Q	0005524	molecular_function	ATP binding
Q	0005737	cellular_component	cytoplasm
Q	0006542	biological_process	glutamine biosynthetic process
Q	0016020	cellular_component	membrane
Q	0016874	molecular_function	ligase activity
Q	0019740	biological_process	nitrogen utilization
Q	0046872	molecular_function	metal ion binding
R	0000166	molecular_function	nucleotide binding
R	0003824	molecular_function	catalytic activity
R	0004356	molecular_function	glutamine synthetase activity
R	0005524	molecular_function	ATP binding
R	0005737	cellular_component	cytoplasm
R	0006542	biological_process	glutamine biosynthetic process
R	0016020	cellular_component	membrane
R	0016874	molecular_function	ligase activity
R	0019740	biological_process	nitrogen utilization
R	0046872	molecular_function	metal ion binding
S	0000166	molecular_function	nucleotide binding
S	0003824	molecular_function	catalytic activity
S	0004356	molecular_function	glutamine synthetase activity
S	0005524	molecular_function	ATP binding
S	0005737	cellular_component	cytoplasm
S	0006542	biological_process	glutamine biosynthetic process
S	0016020	cellular_component	membrane
S	0016874	molecular_function	ligase activity
S	0019740	biological_process	nitrogen utilization
S	0046872	molecular_function	metal ion binding
T	0000166	molecular_function	nucleotide binding
T	0003824	molecular_function	catalytic activity
T	0004356	molecular_function	glutamine synthetase activity
T	0005524	molecular_function	ATP binding
T	0005737	cellular_component	cytoplasm
T	0006542	biological_process	glutamine biosynthetic process
T	0016020	cellular_component	membrane
T	0016874	molecular_function	ligase activity
T	0019740	biological_process	nitrogen utilization
T	0046872	molecular_function	metal ion binding
U	0000166	molecular_function	nucleotide binding
U	0003824	molecular_function	catalytic activity
U	0004356	molecular_function	glutamine synthetase activity
U	0005524	molecular_function	ATP binding
U	0005737	cellular_component	cytoplasm
U	0006542	biological_process	glutamine biosynthetic process
U	0016020	cellular_component	membrane
U	0016874	molecular_function	ligase activity
U	0019740	biological_process	nitrogen utilization
U	0046872	molecular_function	metal ion binding
V	0000166	molecular_function	nucleotide binding
V	0003824	molecular_function	catalytic activity
V	0004356	molecular_function	glutamine synthetase activity
V	0005524	molecular_function	ATP binding
V	0005737	cellular_component	cytoplasm
V	0006542	biological_process	glutamine biosynthetic process
V	0016020	cellular_component	membrane
V	0016874	molecular_function	ligase activity
V	0019740	biological_process	nitrogen utilization
V	0046872	molecular_function	metal ion binding
W	0000166	molecular_function	nucleotide binding
W	0003824	molecular_function	catalytic activity
W	0004356	molecular_function	glutamine synthetase activity
W	0005524	molecular_function	ATP binding
W	0005737	cellular_component	cytoplasm
W	0006542	biological_process	glutamine biosynthetic process
W	0016020	cellular_component	membrane
W	0016874	molecular_function	ligase activity
W	0019740	biological_process	nitrogen utilization
W	0046872	molecular_function	metal ion binding
X	0000166	molecular_function	nucleotide binding
X	0003824	molecular_function	catalytic activity
X	0004356	molecular_function	glutamine synthetase activity
X	0005524	molecular_function	ATP binding
X	0005737	cellular_component	cytoplasm
X	0006542	biological_process	glutamine biosynthetic process
X	0016020	cellular_component	membrane
X	0016874	molecular_function	ligase activity
X	0019740	biological_process	nitrogen utilization
X	0046872	molecular_function	metal ion binding

Functional Information from PDB Data

site_id	AC1
Number of Residues	8
Details	binding site for residue 2K9 A 900

Chain	Residue
A	TYR125
A	PHE228
A	HIS274
A	SER276
A	TRP278
A	LYS357
A	ALA358
A	ARG360

---

site_id	AC2
Number of Residues	6
Details	binding site for residue 2K9 B 900

Chain	Residue
B	HIS274
B	SER276
B	TRP278
B	LYS357
B	ARG360
B	PHE228

---

site_id	AC3
Number of Residues	8
Details	binding site for residue 2K9 C 900

Chain	Residue
C	TYR125
C	PHE228
C	HIS274
C	SER276
C	TRP278
C	LYS357
C	ALA358
C	ARG360

---

site_id	AC4
Number of Residues	8
Details	binding site for residue 2K9 D 900

Chain	Residue
D	TYR125
D	GLY127
D	PHE228
D	HIS274
D	SER276
D	TRP278
D	LYS357
D	ALA358

---

site_id	AC5
Number of Residues	8
Details	binding site for residue 2K9 E 900

Chain	Residue
E	TYR125
E	PHE228
E	HIS274
E	SER276
E	TRP278
E	LYS357
E	ALA358
E	ARG360

---

site_id	AC6
Number of Residues	7
Details	binding site for residue 2K9 F 900

Chain	Residue
F	TYR125
F	PHE228
F	HIS274
F	SER276
F	TRP278
F	ALA358
F	ARG360

---

site_id	AC7
Number of Residues	8
Details	binding site for residue 2K9 G 900

Chain	Residue
G	TYR125
G	PHE228
G	HIS274
G	SER276
G	TRP278
G	LYS357
G	ALA358
G	ARG360

---

site_id	AC8
Number of Residues	9
Details	binding site for residue 2K9 H 900

Chain	Residue
H	TYR125
H	PHE228
H	HIS274
H	GLN275
H	SER276
H	TRP278
H	LYS357
H	ALA358
H	ARG360

---

site_id	AC9
Number of Residues	7
Details	binding site for residue 2K9 I 900

Chain	Residue
I	TYR125
I	PHE228
I	HIS274
I	SER276
I	TRP278
I	LYS357
I	ARG360

---

site_id	AD1
Number of Residues	8
Details	binding site for residue 2K9 J 900

Chain	Residue
J	TYR125
J	PHE228
J	HIS274
J	SER276
J	TRP278
J	LYS357
J	ALA358
J	ARG360

---

site_id	AD2
Number of Residues	8
Details	binding site for residue 2K9 K 900

Chain	Residue
K	TYR125
K	PHE228
K	HIS274
K	SER276
K	TRP278
K	LYS357
K	ALA358
K	ARG360

---

site_id	AD3
Number of Residues	8
Details	binding site for residue 2K9 L 900

Chain	Residue
L	TYR125
L	PHE228
L	HIS274
L	SER276
L	TRP278
L	LYS357
L	ALA358
L	ARG360

---

site_id	AD4
Number of Residues	7
Details	binding site for residue 2K9 M 900

Chain	Residue
M	ARG360
M	TYR125
M	PHE228
M	HIS274
M	GLN275
M	SER276
M	TRP278

---

site_id	AD5
Number of Residues	6
Details	binding site for residue 2K9 N 900

Chain	Residue
N	TYR125
N	PHE228
N	HIS274
N	TRP278
N	ALA358
N	ARG360

---

site_id	AD6
Number of Residues	6
Details	binding site for residue 2K9 O 900

Chain	Residue
O	TYR125
O	PHE228
O	HIS274
O	SER276
O	TRP278
O	ALA358

---

site_id	AD7
Number of Residues	8
Details	binding site for residue 2K9 P 900

Chain	Residue
P	TYR125
P	PHE228
P	HIS274
P	SER276
P	TRP278
P	LYS357
P	ALA358
P	ARG360

---

site_id	AD8
Number of Residues	5
Details	binding site for residue 2K9 Q 900

Chain	Residue
Q	TYR125
Q	PHE228
Q	SER276
Q	TRP278
Q	ALA358

---

site_id	AD9
Number of Residues	9
Details	binding site for residue 2K9 R 900

Chain	Residue
R	TYR125
R	GLY127
R	PHE228
R	HIS274
R	SER276
R	TRP278
R	LYS357
R	ALA358
R	ARG360

---

site_id	AE1
Number of Residues	7
Details	binding site for residue 2K9 S 900

Chain	Residue
S	TYR125
S	PHE228
S	HIS274
S	SER276
S	TRP278
S	ALA358
S	ARG360

---

site_id	AE2
Number of Residues	8
Details	binding site for residue 2K9 T 900

Chain	Residue
T	TYR125
T	GLY127
T	PHE228
T	HIS274
T	SER276
T	TRP278
T	LYS357
T	ARG360

---

site_id	AE3
Number of Residues	7
Details	binding site for residue 2K9 U 900

Chain	Residue
U	TYR125
U	PHE228
U	HIS274
U	SER276
U	TRP278
U	ALA358
U	ARG360

---

site_id	AE4
Number of Residues	9
Details	binding site for residue 2K9 V 900

Chain	Residue
V	TYR125
V	LYS211
V	PHE228
V	HIS274
V	SER276
V	TRP278
V	LYS357
V	ALA358
V	ARG360

---

site_id	AE5
Number of Residues	8
Details	binding site for residue 2K9 W 900

Chain	Residue
W	TYR125
W	PHE228
W	HIS274
W	SER276
W	TRP278
W	LYS357
W	ALA358
W	ARG360

---

site_id	AE6
Number of Residues	9
Details	binding site for residue 2K9 X 900

Chain	Residue
X	TYR125
X	GLY127
X	PHE228
X	HIS274
X	SER276
X	TRP278
X	LYS357
X	ALA358
X	ARG360

---

Functional Information from PROSITE/UniProt

site_id	PS00180
Number of Residues	19
Details	GLNA_1 Glutamine synthetase signature 1. FDGSSirgfqsihESDmlL

Chain	Residue	Details
A	PHE49-LEU67

---

site_id	PS00181
Number of Residues	16
Details	GLNA_ATP Glutamine synthetase putative ATP-binding region signature. KPLfgd..NGSGmHchqS

Chain	Residue	Details
A	LYS261-SER276

---

site_id	PS00182
Number of Residues	13
Details	GLNA_ADENYLATION Glutamine synthetase class-I adenylation site. KIepqapVDKDLY

Chain	Residue	Details
A	LYS390-TYR402

---

Functional Information from SwissProt/UniProt

site_id	SWS_FT_FI1
Number of Residues	8880
Details	Domain: {"description":"GS catalytic","evidences":[{"source":"PROSITE-ProRule","id":"PRU01331","evidenceCode":"ECO:0000255"}]}

Chain

Residue

Details

---

site_id	SWS_FT_FI2
Number of Residues	384
Details	Binding site: {"evidences":[{"source":"UniProtKB","id":"P9WN39","evidenceCode":"ECO:0000250"}]}

Chain

Residue

Details

---

site_id	SWS_FT_FI3
Number of Residues	24
Details	Binding site: {"evidences":[{"source":"UniProtKB","id":"P12425","evidenceCode":"ECO:0000250"}]}

Chain

Residue

Details

---

site_id	SWS_FT_FI4
Number of Residues	48
Details	Binding site: {"evidences":[{"source":"UniProtKB","id":"P77961","evidenceCode":"ECO:0000250"}]}

Chain

Residue

Details

---

site_id	SWS_FT_FI5
Number of Residues	24
Details	Binding site: {"evidences":[{"source":"UniProtKB","id":"P0A1P6","evidenceCode":"ECO:0000250"}]}

Chain

Residue

Details

---

site_id	SWS_FT_FI6
Number of Residues	24
Details	Modified residue: {"description":"O-AMP-tyrosine","evidences":[{"source":"UniProtKB","id":"P9WN39","evidenceCode":"ECO:0000250"}]}

Chain

Residue

Details

---