SInCRe - Rv2763c

Tuberculist information

Gene name	dfrA
Protein function	Dihydrofolate reductase DfrA (DHFR) (tetrahydrofolate dehydrogenase)
Functional category(tuberculist)	intermediary metabolism and respiration
Gene location(kb)	3073.13
Molecular mass(da)	17640
External sites	TB Database TubercuList WebTB

Protein sequence

Number of amino acids : 159

	  		  	1    MVGLIWAQATSGVIGRGGDIPWRLPEDQAHFREITMGHTIVMGRRTWDSLPAKVRPLPGR   60
			  	61   RNVVLSRQADFMASGAEVVGSLEEALTSPETWVIGGGQVYALALPYATRCEVTEVDIGLP  120
			  	121  REAGDALAPVLDETWRGETGEWRFSRSGLRYRLYSYHRS

Known structures in the PDB

	PDB ID	1DF7
	Total residue count	159
	Number of chains	1
	Method	X-RAY
	Resolution	1.7

	PDB ID	1DG5
	Total residue count	159
	Number of chains	1
	Method	X-RAY
	Resolution	2

	PDB ID	1DG7
	Total residue count	159
	Number of chains	1
	Method	X-RAY
	Resolution	1.8

	PDB ID	1DG8
	Total residue count	159
	Number of chains	1
	Method	X-RAY
	Resolution	2

	PDB ID	2CIG
	Total residue count	159
	Number of chains	1
	Method	X-RAY
	Resolution	1.9

	PDB ID	4KL9
	Total residue count	179
	Number of chains	1
	Method	X-RAY
	Resolution	1.39

	PDB ID	4KLX
	Total residue count	358
	Number of chains	2
	Method	X-RAY
	Resolution	1.23

	PDB ID	4KM0
	Total residue count	358
	Number of chains	2
	Method	X-RAY
	Resolution	1.3

	PDB ID	4KM2
	Total residue count	358
	Number of chains	2
	Method	X-RAY
	Resolution	1.4

	PDB ID	4KNE
	Total residue count	358
	Number of chains	2
	Method	X-RAY
	Resolution	2

Number of amino acids : 159

Domains assigned based on sequence.

Mtb Structural proteome models

CHOPIN models

Profile-based domain assignment

Structural/Functional domain family	Pfam acc.no./SCOP ID	Domain Region
DHFR_1	PF00186	1-158

Mtb Structural Proteome models

Model Number	1
Model name	Rv2763c_1df7_A
Template	1DF7 APDB CREDO
Template coverage	1_159
Template Identity(%)	100.0
Model coverage(%)	99.4
Normalized DOPE score	-1.958

Model Number	2
Model name	Rv2763c
Template	1DF7 APDB CREDO
Template coverage	1_159
Template Identity(%)	100.0
Model coverage(%)	99.4
Normalized DOPE score	-1.685

Structure Models from Chopin

Model Number	1
Profile	c.71.1.1 - 3.40.430.10 Click for model details
zscore	30.16
Residue begin	1
Residue end	159

Binding pockets

STRING

Cytoscape Web will replace the contents of this div with protein-protein interaction network.

Protein interacting with Rv2763c	Gene name	Confidence Score
Rv2764c	thyA	0.999
Rv2447c	folC	0.993
Rv2447c	folC	0.993
Rv1406	fmt	0.99
Rv1406	fmt	0.99
Rv2754c	thyX	0.989
Rv3608c	folP1	0.987
Rv0070c	glyA2	0.983
Rv1093	glyA1	0.982
Rv2211c	gcvT	0.981
Rv2211c	gcvT	0.981
Rv3606c	folK	0.964
Rv2964	purU	0.957
Rv2964	purU	0.957
Rv2124c	metH	0.952
Rv1207	folP2	0.952
Rv2124c	metH	0.952
Rv2124c	metH	0.952
Rv2124c	metH	0.952
Rv2124c	metH	0.952
Rv0389	purT	0.949
Rv0956	purN	0.948
Rv2981c	ddlA	0.936
Rv2981c	ddlA	0.936
Rv2786c	ribF	0.932
Rv2786c	ribF	0.932
Rv2448c	valS	0.918
Rv2448c	valS	0.918
Rv2448c	valS	0.918
Rv3051c	nrdE	0.916
Rv3356c	folD	0.916
Rv3356c	folD	0.916
Rv3051c	nrdE	0.916
Rv3051c	nrdE	0.916
Rv0957	purH	0.912
Rv0957	purH	0.912

Potential ligand/drug binding sites

Protein Model	Pocket Number	Drug Binding Site	PMIN Score	Pvalue PMIN	PMAX Score	Pvalue PMAX
Rv2763c_1df7_A	2	2xkw_P1B_A_1478 PDB CREDO	0.706	0.076	0.655	0.001
Rv2763c_1df7_A	2	1xkk_FMM_A_91 PDB CREDO	0.687	0.091	0.621	0.001
Rv2763c_1df7_A	2	3sm2_478_A_126 PDB CREDO	0.636	0.138	0.606	0.002
Rv2763c_1df7_A	2	3bjw_SVR_B_501 PDB CREDO	0.653	0.121	0.591	0.002
Rv2763c_1df7_A	2	3bjw_SVR_H_504 PDB CREDO	0.653	0.122	0.590	0.003
Rv2763c_1df7_A	2	1ya4_CTX_A_1 PDB CREDO	0.605	0.173	0.590	0.003
Rv2763c_1df7_A	2	3bjw_SVR_F_502 PDB CREDO	0.651	0.124	0.588	0.003
Rv2763c_1df7_A	2	3cs9_NIL_D_600 PDB CREDO	0.680	0.097	0.583	0.003
Rv2763c_1df7_A	2	1t46_STI_A_3 PDB CREDO	0.676	0.100	0.580	0.003
Rv2763c_1df7_A	2	3cs9_NIL_C_600 PDB CREDO	0.676	0.100	0.580	0.003
Rv2763c_1df7_A	2	3b0w_DGX_B_1 PDB CREDO	0.753	0.046	0.580	0.003
Rv2763c_1df7_A	2	1skx_RFP_A_1 PDB CREDO	0.709	0.074	0.576	0.003
Rv2763c_1df7_A	2	3kk6_CEL_A_701 PDB CREDO	0.633	0.142	0.572	0.003
Rv2763c_1df7_A	2	3cs9_NIL_B_600 PDB CREDO	0.703	0.079	0.572	0.003
Rv2763c_1df7_A	2	2qxs_RAL_A_600 PDB CREDO	0.702	0.080	0.571	0.004
Rv2763c_1df7_A	2	2qxs_RAL_B_600 PDB CREDO	0.699	0.082	0.568	0.004
Rv2763c_1df7_A	2	3bjw_SVR_E_503 PDB CREDO	0.680	0.097	0.568	0.004
Rv2763c_1df7_A	2	3cs9_NIL_A_600 PDB CREDO	0.718	0.068	0.568	0.004
Rv2763c_1df7_A	2	3gp0_NIL_A_1 PDB CREDO	0.643	0.131	0.567	0.004
Rv2763c_1df7_A	2	3kk6_CEL_B_1701 PDB CREDO	0.689	0.089	0.560	0.004
Rv2763c_1df7_A	2	1opj_STI_B_4 PDB CREDO	0.707	0.075	0.560	0.004
Rv2763c_1df7_A	2	1tco_FK5_C_509 PDB CREDO	0.600	0.178	0.557	0.004
Rv2763c_1df7_A	2	1opj_STI_A_3 PDB CREDO	0.699	0.081	0.553	0.005
Rv2763c_1df7_A	2	2v0z_C41_C_1328 PDB CREDO	0.581	0.202	0.553	0.005
Rv2763c_1df7_A	2	1c6z_ROC_B_505 PDB CREDO	0.558	0.233	0.544	0.006
Rv2763c_1df7_A	2	3nxu_RIT_A_600 PDB CREDO	0.669	0.107	0.544	0.006
Rv2763c_1df7_A	2	3nxu_RIT_B_600 PDB CREDO	0.663	0.112	0.539	0.006
Rv2763c_1df7_A	2	1uwj_BAX_A_1723 PDB CREDO	0.720	0.067	0.538	0.006
Rv2763c_1df7_A	2	3k5v_STI_A_2 PDB CREDO	0.698	0.082	0.537	0.006
Rv2763c_1df7_A	2	2v0z_C41_O_1327 PDB CREDO	0.603	0.176	0.531	0.007
Rv2763c_1df7_A	2	3mss_STI_B_1 PDB CREDO	0.722	0.065	0.525	0.007
Rv2763c_1df7_A	2	1iep_STI_B_202 PDB CREDO	0.722	0.065	0.525	0.007
Rv2763c_1df7_A	2	3pyy_STI_A_3 PDB CREDO	0.721	0.065	0.525	0.007
Rv2763c_1df7_A	2	3mss_STI_D_1 PDB CREDO	0.721	0.066	0.524	0.008
Rv2763c_1df7_A	2	3mss_STI_A_1 PDB CREDO	0.720	0.066	0.524	0.008
Rv2763c_1df7_A	2	3k5v_STI_B_2 PDB CREDO	0.720	0.067	0.523	0.008
Rv2763c_1df7_A	2	3ms9_STI_A_1 PDB CREDO	0.719	0.067	0.523	0.008
Rv2763c_1df7_A	2	3mss_STI_C_1 PDB CREDO	0.719	0.067	0.523	0.008
Rv2763c_1df7_A	2	1iep_STI_A_201 PDB CREDO	0.718	0.068	0.522	0.008
Rv2763c_1df7_A	2	3gvu_STI_A_1001 PDB CREDO	0.717	0.069	0.521	0.008
Rv2763c_1df7_A	2	2hyy_STI_A_600 PDB CREDO	0.715	0.070	0.520	0.008
Rv2763c_1df7_A	2	3ms9_STI_B_1 PDB CREDO	0.714	0.070	0.519	0.008
Rv2763c_1df7_A	2	3pyy_STI_B_4 PDB CREDO	0.714	0.070	0.519	0.008
Rv2763c_1df7_A	2	2hyy_STI_C_600 PDB CREDO	0.713	0.071	0.519	0.008
Rv2763c_1df7_A	2	2q64_1UN_B_1001 PDB CREDO	0.529	0.274	0.516	0.009
Rv2763c_1df7_A	2	3b0w_DGX_A_1 PDB CREDO	0.753	0.046	0.516	0.009
Rv2763c_1df7_A	2	2hyy_STI_D_600 PDB CREDO	0.710	0.073	0.516	0.009
Rv2763c_1df7_A	2	2w8y_486_A_1000 PDB CREDO	0.752	0.046	0.516	0.009
Rv2763c_1df7_A	2	2pyn_1UN_A_1001 PDB CREDO	0.528	0.275	0.516	0.009
Rv2763c_1df7_A	2	2pym_1UN_A_1001 PDB CREDO	0.528	0.276	0.515	0.009
Rv2763c_1df7_A	2	2qak_1UN_A_1001 PDB CREDO	0.528	0.276	0.515	0.009
Rv2763c_1df7_A	2	2q63_1UN_A_1001 PDB CREDO	0.528	0.276	0.515	0.009
Rv2763c_1df7_A	2	3oez_STI_A_601 PDB CREDO	0.708	0.075	0.515	0.009
Rv2763c_1df7_A	2	1y0x_T44_X_500 PDB CREDO	0.793	0.027	0.512	0.009
Rv2763c_1df7_A	2	3prs_RIT_A_1001 PDB CREDO	0.510	0.303	0.510	0.009
Rv2763c_1df7_A	2	2nnk_ROC_A_401 PDB CREDO	0.535	0.265	0.510	0.009
Rv2763c_1df7_A	2	3ndt_ROC_D_100 PDB CREDO	0.534	0.267	0.509	0.010
Rv2763c_1df7_A	2	3ufn_ROC_A_401 PDB CREDO	0.575	0.210	0.506	0.010
Rv2763c_1df7_A	2	1uwj_BAX_B_1723 PDB CREDO	0.735	0.056	0.504	0.010
Rv2763c_1df7_A	2	3d91_REM_A_350 PDB CREDO	0.734	0.058	0.503	0.010
Rv2763c_1df7_A	2	3d91_REM_B_350 PDB CREDO	0.733	0.058	0.503	0.010
Rv2763c_1df7_A	2	3h52_486_B_1 PDB CREDO	0.755	0.045	0.503	0.010
Rv2763c_1df7_A	2	2oiq_STI_A_1001 PDB CREDO	0.753	0.046	0.501	0.011

Similarity to known drug target from sensitive sequence analysis

No drug targets

List of small molecules tested from TIBLE

View results in TIBLE page

Name	Affinity	Assay description	DOI
CHEMBL1162949	IZ = 5 mm	Inhibition of Mycobacterium tuberculosis DHFR expressed in Saccharomyces cerevisiae TB5 assessed as yeast growth inhibition after 3 days by radial spoke assay	http://www.ncbi.nlm.nih.gov/pubmed/17451962
CHEMBL21408	IZ = 7 mm	Inhibition of Mycobacterium tuberculosis DHFR expressed in Saccharomyces cerevisiae TB5 assessed as yeast growth inhibition after 3 days by radial spoke assay	http://www.ncbi.nlm.nih.gov/pubmed/17451962
CHEMBL22	IZ = 5 mm	Inhibition of Mycobacterium tuberculosis DHFR expressed in Saccharomyces cerevisiae TB5 assessed as yeast growth inhibition after 3 days by radial spoke assay	http://www.ncbi.nlm.nih.gov/pubmed/17451962
CHEMBL226147	IZ = 11 mm	Inhibition of Mycobacterium tuberculosis DHFR expressed in Saccharomyces cerevisiae TB5 assessed as yeast growth inhibition after 3 days by radial spoke assay	http://www.ncbi.nlm.nih.gov/pubmed/17451962
CHEMBL226198	IZ = 7 mm	Inhibition of Mycobacterium tuberculosis DHFR expressed in Saccharomyces cerevisiae TB5 assessed as yeast growth inhibition after 3 days by radial spoke assay	http://www.ncbi.nlm.nih.gov/pubmed/17451962
CHEMBL226199	IZ = 8 mm	Inhibition of Mycobacterium tuberculosis DHFR expressed in Saccharomyces cerevisiae TB5 assessed as yeast growth inhibition after 3 days by radial spoke assay	http://www.ncbi.nlm.nih.gov/pubmed/17451962
CHEMBL226200	IZ = 7 mm	Inhibition of Mycobacterium tuberculosis DHFR expressed in Saccharomyces cerevisiae TB5 assessed as yeast growth inhibition after 3 days by radial spoke assay	http://www.ncbi.nlm.nih.gov/pubmed/17451962
CHEMBL226249	IZ = 7 mm	Inhibition of Mycobacterium tuberculosis DHFR expressed in Saccharomyces cerevisiae TB5 assessed as yeast growth inhibition after 3 days by radial spoke assay	http://www.ncbi.nlm.nih.gov/pubmed/17451962
CHEMBL226250	IZ = 8 mm	Inhibition of Mycobacterium tuberculosis DHFR expressed in Saccharomyces cerevisiae TB5 assessed as yeast growth inhibition after 3 days by radial spoke assay	http://www.ncbi.nlm.nih.gov/pubmed/17451962
CHEMBL226251	IZ = 9 mm	Inhibition of Mycobacterium tuberculosis DHFR expressed in Saccharomyces cerevisiae TB5 assessed as yeast growth inhibition after 3 days by radial spoke assay	http://www.ncbi.nlm.nih.gov/pubmed/17451962
CHEMBL226252	IZ = 8 mm	Inhibition of Mycobacterium tuberculosis DHFR expressed in Saccharomyces cerevisiae TB5 assessed as yeast growth inhibition after 3 days by radial spoke assay	http://www.ncbi.nlm.nih.gov/pubmed/17451962
CHEMBL226312	IZ = 5 mm	Inhibition of Mycobacterium tuberculosis DHFR expressed in Saccharomyces cerevisiae TB5 assessed as yeast growth inhibition after 3 days by radial spoke assay	http://www.ncbi.nlm.nih.gov/pubmed/17451962
CHEMBL278847	IZ = 5 mm	Inhibition of Mycobacterium tuberculosis DHFR expressed in Saccharomyces cerevisiae TB5 assessed as yeast growth inhibition after 3 days by radial spoke assay	http://www.ncbi.nlm.nih.gov/pubmed/17451962
CHEMBL387508	IZ = 9 mm	Inhibition of Mycobacterium tuberculosis DHFR expressed in Saccharomyces cerevisiae TB5 assessed as yeast growth inhibition after 3 days by radial spoke assay	http://www.ncbi.nlm.nih.gov/pubmed/17451962
CHEMBL387509	IZ = 9 mm	Inhibition of Mycobacterium tuberculosis DHFR expressed in Saccharomyces cerevisiae TB5 assessed as yeast growth inhibition after 3 days by radial spoke assay	http://www.ncbi.nlm.nih.gov/pubmed/17451962
CHEMBL388407	IZ = 5 mm	Inhibition of Mycobacterium tuberculosis DHFR expressed in Saccharomyces cerevisiae TB5 assessed as yeast growth inhibition after 3 days by radial spoke assay	http://www.ncbi.nlm.nih.gov/pubmed/17451962
CHEMBL388840	IZ = 8 mm	Inhibition of Mycobacterium tuberculosis DHFR expressed in Saccharomyces cerevisiae TB5 assessed as yeast growth inhibition after 3 days by radial spoke assay	http://www.ncbi.nlm.nih.gov/pubmed/17451962
CHEMBL389063	IZ = 8 mm	Inhibition of Mycobacterium tuberculosis DHFR expressed in Saccharomyces cerevisiae TB5 assessed as yeast growth inhibition after 3 days by radial spoke assay	http://www.ncbi.nlm.nih.gov/pubmed/17451962
CHEMBL427445	IZ = 5 mm	Inhibition of Mycobacterium tuberculosis DHFR expressed in Saccharomyces cerevisiae TB5 assessed as yeast growth inhibition after 3 days by radial spoke assay	http://www.ncbi.nlm.nih.gov/pubmed/17451962
CHEMBL64	Ki = 1 nM	Inhibition of Mycobacterium tuberculosis dihydrofolate reductase	http://www.ncbi.nlm.nih.gov/pubmed/20566771

Off-target activity - ligand based from TIBLE

View results in TIBLE page

Predicted off-target	Method	Summary	Full results
Glutathione-requiring prostaglandin D synthase 1V40	PharmMapper	1 hydroph + 4 HB + 3 pos/neg + 0 arom	Link
Serum albumin 1GNJ	PharmMapper	6 hydroph + 1 HB + 1 pos/neg + 0 arom	Link
Lactoylglutathione lyase 1FRO	PharmMapper	3 hydroph + 4 HB + 2 pos/neg + 0 arom	Link
Cellular retinoic acid-binding protein 2 3CBS	PharmMapper	6 hydroph + 2 HB + 1 pos/neg + 0 arom	Link
Coagulation factor VII 1DAN	PharmMapper	0 hydroph + 7 HB + 5 pos/neg + 0 arom	Link
Maillard reaction	PASS	Pa = 0.795 & SM = CHEMBL64	Link
Peroxidase	PASS	Pa = 0.723 & SM = CHEMBL64	Link
formyl peptide receptor; N-formyl-Met-Leu-Phe receptor [-]	SEA	E_value = 9.83e-19 & MaxTC = 0.37	Link

Small molecules involved in protein-protein complex from TIMBAL .Proteins similar to Mtb based on sequence analysis.

Data not available

STITCH interactions

Chemical Name	Confidence score	Molecular Weight
methotrexatePubChem	0.997	454.439
trimethoprimPubChem	0.997	290.318
dihydrofolatePubChem	0.997	443.413
NADP(H)PubChem	0.997	745.421
NADPPubChem	0.995	744.413
DB04007PubChem	0.979	370.245
tetrahydrofolatePubChem	0.977	445.429
glycerolPubChem	0.977	92.0938
folatePubChem	0.971	441.397
hydroxyl radicalsPubChem	0.966	17.0073
phosphatePubChem	0.961	96.9872
thymidylatePubChem	0.958	322.208
dihydropteroatePubChem	0.947	314.299
sulfatePubChem	0.946	96.0626
H(+)PubChem	0.942	2.01588
deuteriumPubChem	0.941	2.01588
trimetrexatePubChem	0.939	370.426
hydron sulfatePubChem	0.934	196.157
dUMPPubChem	0.932	308.182
H4FPubChem	0.93	445.429
glutamatePubChem	0.929	147.129
5,10-methylenetetrahydrofolatePubChem	0.928	457.44
reduced nicotinamide adenine dinucleotidePubChem	0.923	665.441
N5,N10-methylenetetrahydrofolatePubChem	0.913	457.44
polyglycinePubChem	0.902	75.0666
carbon dioxidePubChem	0.902	44.0095
adenosine diphosphatePubChem	0.901	427.201
1dGPubChem	0.9	850.515
DL-serinePubChem	0.9	105.093
NAD+PubChem	0.9	663.425
L-serinePubChem	0.9	105.093
dihydronicotinamide formycin dinucleotidePubChem	0.9	665.441
protiumPubChem	0.9	2.01576
adenosine triphosphatePubChem	0.9	507.181
ammoniaPubChem	0.9	17.0305
5-deazafolatePubChem	0.879	440.409
piritreximPubChem	0.878	325.365
5,10-dideaza-5,6,7,8-tetrahydrofolic acidPubChem	0.871	443.453
methotrexate polyglutamatePubChem	0.857	454.439
aminopterinPubChem	0.853	440.413
edatrexatePubChem	0.842	467.478
10-ethyl-10-deazaaminopterinPubChem	0.837	467.478
CAS 59-05-2PubChem	0.818	454.439
5-deazafolic acidPubChem	0.818	440.409
7,8-dihydrobiopterinPubChem	0.8	239.231
calciumPubChem	0.794	40.078
DB08234PubChem	0.793	312.366
PT523PubChem	0.792	573.56
53RPubChem	0.781	358.436
(E)-3-[5-[(2,4-diaminopyrimidin-5-yl)methyl]-2,3-dimethoxyphenyl]-1-(1-propyl-1H-phthalazin-2-yl)proPubChem	0.778	486.565
(E)-3-[5-[(2,4-diaminopyrimidin-5-yl)methyl]-2,3-dimethoxyphenyl]-1-[(1S)-1-propyl-1H-phthalazin-2-yPubChem	0.778	486.565
11fPubChem	0.778	358.436
AR-709PubChem	0.777	534.994
CB3717PubChem	0.774	477.469
Propargyl inhibitor, 20PubChem	0.774	342.392
pyrimethaminePubChem	0.773	248.711
Vg9PubChem	0.773	368.433
CB 3717PubChem	0.772	477.469
GW578PubChem	0.771	282.363
trimethoprim-sulfamethoxazolePubChem	0.771	543.595
methylbenzoprimPubChem	0.767	378.428
53TPubChem	0.767	386.489
2,4-diamino-PubChem	0.765	386.489
sulfamethoxazolePubChem	0.764	253.278
iclaprimPubChem	0.756	354.403
52vPubChem	0.755	386.489
5WBPubChem	0.753	358.392
metoprinePubChem	0.747	269.13
5-deazaaminopterinPubChem	0.744	439.425
5WAPubChem	0.737	344.365
Aids032361PubChem	0.727	302.782
CHEMBL13908PubChem	0.727	418.487
CHEMBL23338PubChem	0.727	300.356
CHEMBL60069PubChem	0.727	318.371
CHEMBL14201PubChem	0.727	334.327
CHEMBL23609PubChem	0.727	304.344
10-deazaaminopterinPubChem	0.726	439.425
Ro 11-8958PubChem	0.725	353.418
5,8-dideazafolic acidPubChem	0.717	439.421
2,4-diaminopyrimidinePubChem	0.716	110.117
cycloguanilPubChem	0.714	288.176
brodimoprimPubChem	0.714	339.188
derivative of methotrexatePubChem	0.71	569.527
methotrexate-gamma-aspartatePubChem	0.706	569.527
Aids031008PubChem	0.704	349.218
deazaaminopterinPubChem	0.703	438.437
CHEBI:669256PubChem	0.7	356.419
CHEBI:669926PubChem	0.7	356.419