SInCRe - Rv0006

Tuberculist information

Gene name	gyrA
Protein function	DNA gyrase (subunit A) GyrA (DNA topoisomerase (ATP-hydrolysing)) (DNA topoisomerase II) (type II DNA topoisomerase)
Functional category(tuberculist)	information pathways
Gene location(kb)	7.302
Molecular mass(da)	92274.3
External sites	TB Database TubercuList WebTB

Protein sequence

Number of amino acids : 838

	  		  	1    MTDTTLPPDDSLDRIEPVDIEQEMQRSYIDYAMSVIVGRALPEVRDGLKPVHRRVLYAMF   60
			  	61   DSGFRPDRSHAKSARSVAETMGNYHPHGDASIYDSLVRMAQPWSLRYPLVDGQGNFGSPG  120
			  	121  NDPPAAMRYTEARLTPLAMEMLREIDEETVDFIPNYDGRVQEPTVLPSRFPNLLANGSGG  180
			  	181  IAVGMATNIPPHNLRELADAVFWALENHDADEEETLAAVMGRVKGPDFPTAGLIVGSQGT  240
			  	241  ADAYKTGRGSIRMRGVVEVEEDSRGRTSLVITELPYQVNHDNFITSIAEQVRDGKLAGIS  300
			  	301  NIEDQSSDRVGLRIVIEIKRDAVAKVVINNLYKHTQLQTSFGANMLAIVDGVPRTLRLDQ  360
			  	361  LIRYYVDHQLDVIVRRTTYRLRKANERAHILRGLVKALDALDEVIALIRASETVDIARAG  420
			  	421  LIELLDIDEIQAQAILDMQLRRLAALERQRIIDDLAKIEAEIADLEDILAKPERQRGIVR  480
			  	481  DELAEIVDRHGDDRRTRIIAADGDVSDEDLIAREDVVVTITETGYAKRTKTDLYRSQKRG  540
			  	541  GKGVQGAGLKQDDIVAHFFVCSTHDLILFFTTQGRVYRAKAYDLPEASRTARGQHVANLL  600
			  	601  AFQPEERIAQVIQIRGYTDAPYLVLATRNGLVKKSKLTDFDSNRSGGIVAVNLRDNDELV  660
			  	661  GAVLCSAGDDLLLVSANGQSIRFSATDEALRPMGRATSGVQGMRFNIDDRLLSLNVVREG  720
			  	721  TYLLVATSGGYAKRTAIEEYPVQGRGGKGVLTVMYDRRRGRLVGALIVDDDSELYAVTSG  780
			  	781  GGVIRTAARQVRKAGRQTKGVRLMNLGEGDTLLAIARNAEESGDDNAVDANGADQTGN

Known structures in the PDB

	PDB ID	3IFZ
	Total residue count	1016
	Number of chains	2
	Method	X-RAY
	Resolution	2.7

	PDB ID	3ILW
	Total residue count	940
	Number of chains	2
	Method	X-RAY
	Resolution	1.6

	PDB ID	3UC1
	Total residue count	327
	Number of chains	1
	Method	X-RAY
	Resolution	1.65

	PDB ID	4G3N
	Total residue count	327
	Number of chains	1
	Method	X-RAY
	Resolution	1.4

Number of amino acids : 838

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
DNA_topoisoIV	PF00521	39-484
DNA_gyraseA_C	PF03989	515-562
DNA_gyraseA_C	PF03989	565-603
DNA_gyraseA_C	PF03989	621-666
DNA_gyraseA_C	PF03989	669-718
DNA_gyraseA_C	PF03989	721-769
DNA_gyraseA_C	PF03989	772-817

Mtb Structural Proteome models

Model Number	1
Model name	Rv0006_3ilw_A
Template	3ILW APDB CREDO
Template coverage	37_500
Template Identity(%)	100.0
Model coverage(%)	55.3
Normalized DOPE score	-1.77

Model Number	2
Model name	Rv0006.4
Template	1SUU APDB CREDO
Template coverage	506_807
Template Identity(%)	27.8
Model coverage(%)	36.2
Normalized DOPE score	-0.49

Model Number	3
Model name	Rv0006.3
Template	1WP5 APDB CREDO
Template coverage	1_317
Template Identity(%)	25.9
Model coverage(%)	38.2
Normalized DOPE score	-0.086

Model Number	4
Model name	Rv0006
Template	1ZVU APDB CREDO
Template coverage	28_737
Template Identity(%)	34.5
Model coverage(%)	86.4
Normalized DOPE score	0.351

Structure Models from Chopin

Model Number	1
Profile	e.11.1.1 - 1.10.268.10 Click for model details
zscore	70.53
Residue begin	39
Residue end	484

Model Number	2
Profile	b.68.10.1 - 2.120.10.90 Click for model details
zscore	11.3
Residue begin	1
Residue end	46

Model Number	3
Profile	b.68.10.1 - 2.120.10.90 Click for model details
zscore	11.3
Residue begin	515
Residue end	560

Model Number	4
Profile	b.68.10.1 - 2.120.10.90 Click for model details
zscore	11.3
Residue begin	621
Residue end	666

Model Number	5
Profile	b.68.10.1 - 2.120.10.90 Click for model details
zscore	11.3
Residue begin	669
Residue end	714

Model Number	6
Profile	b.68.10.1 - 2.120.10.90 Click for model details
zscore	11.3
Residue begin	721
Residue end	766

Model Number	7
Profile	b.68.10.1 - 2.120.10.90 Click for model details
zscore	11.3
Residue begin	772
Residue end	817

Binding pockets

STRING

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

Protein interacting with Rv0006	Gene name	Confidence Score
Rv0005	gyrB	0.999
Rv0005	gyrB	0.999
Rv0005	gyrB	0.999
Rv0005	gyrB	0.999
Rv0002	dnaN	0.996
Rv0002	dnaN	0.996
Rv0002	dnaN	0.996
Rv0003	recF	0.996
Rv0001	dnaA	0.993
Rv0001	dnaA	0.993
Rv0667	rpoB	0.979
Rv0667	rpoB	0.979
Rv0667	rpoB	0.979
Rv0667	rpoB	0.979
Rv0667	rpoB	0.979
Rv0667	rpoB	0.979
Rv0058	dnaB	0.978
Rv0058	dnaB	0.978
Rv0058	dnaB	0.978
Rv0058	dnaB	0.978
Rv1656	argF	0.972
Rv1656	argF	0.972
Rv0682	rpsL	0.97
Rv1630	rpsA	0.967
Rv0440	groEL2	0.957
Rv3834c	serS	0.955
Rv3834c	serS	0.955
Rv2428	ahpC	0.954
Rv2678c	hemE	0.95
Rv2043c	pncA	0.939
Rv3100c	smpB	0.939
Rv1908c	katG	0.938
Rv0054	ssb	0.938
Rv1649	pheS	0.938
Rv1649	pheS	0.938
Rv2720	lexA	0.933
Rv2720	lexA	0.933
Rv1547	dnaE1	0.932
Rv1547	dnaE1	0.932
Rv1547	dnaE1	0.932
Rv1007c	metS	0.932
Rv1547	dnaE1	0.932
Rv3608c	folP1	0.931
Rv0684	fusA1	0.93
Rv0684	fusA1	0.93
Rv0684	fusA1	0.93
Rv0684	fusA1	0.93
Rv0684	fusA1	0.93
Rv3646c	topA	0.926
Rv3646c	topA	0.926
Rv3646c	topA	0.926
Rv0350	dnaK	0.924
Rv3924c	rpmH	0.923
Rv2538c	aroB	0.92
Rv1638	uvrA	0.915
Rv3674c	nth	0.906
Rv3674c	nth	0.906
Rv3674c	nth	0.906
Rv2737c	recA	0.905
Rv2737c	recA	0.905
Rv0685	tuf	0.902
Rv0685	tuf	0.902
Rv0685	tuf	0.902
Rv1650	pheT	0.901
Rv1650	pheT	0.901
Rv1650	pheT	0.901
Rv1650	pheT	0.901

Potential ligand/drug binding sites

Protein Model	Pocket Number	Drug Binding Site	PMIN Score	Pvalue PMIN	PMAX Score	Pvalue PMAX
Rv0006.3	10	2itz_IRE_A_2021 PDB CREDO	0.686	0.092	0.580	0.003
Rv0006.3	10	1rv7_AB1_B_1001 PDB CREDO	0.638	0.137	0.561	0.004
Rv0006.3	10	3ads_IMN_B_3 PDB CREDO	0.584	0.199	0.559	0.004
Rv0006.3	10	2ity_IRE_A_2020 PDB CREDO	0.688	0.090	0.558	0.004
Rv0006_3ilw_A	2	1fr6_AZR_A_362 PDB CREDO	0.579	0.205	0.557	0.004
Rv0006_3ilw_A	2	2c49_ADN_A_1301 PDB CREDO	0.553	0.240	0.553	0.005
Rv0006_3ilw_A	2	2w26_RIV_A_1001 PDB CREDO	0.548	0.246	0.548	0.005
Rv0006_3ilw_A	2	1fr6_AZR_B_362 PDB CREDO	0.569	0.218	0.548	0.005
Rv0006_3ilw_A	1	2xn3_ID8_A_1356 PDB CREDO	0.611	0.166	0.544	0.005
Rv0006.3	10	1ie4_T44_A_128 PDB CREDO	0.608	0.170	0.535	0.006
Rv0006_3ilw_A	2	3fuu_ADN_A_0 PDB CREDO	0.533	0.268	0.533	0.007
Rv0006.3	10	3uq6_ADN_A_401 PDB CREDO	0.610	0.167	0.532	0.007
Rv0006_3ilw_A	2	1jin_KTN_A_801 PDB CREDO	0.553	0.240	0.532	0.007
Rv0006_3ilw_A	1	2w03_ADN_A_1588 PDB CREDO	0.663	0.112	0.529	0.007
Rv0006_3ilw_A	2	1bx4_ADN_A_350 PDB CREDO	0.677	0.099	0.529	0.007
Rv0006.3	10	3sxr_1N1_B_2 PDB CREDO	0.625	0.150	0.528	0.007
Rv0006_3ilw_A	2	4e3a_ADN_B_500 PDB CREDO	0.565	0.224	0.523	0.008
Rv0006_3ilw_A	1	2it4_PPF_A_500 PDB CREDO	0.522	0.284	0.522	0.008
Rv0006.3	10	3uq6_ADN_B_401 PDB CREDO	0.598	0.181	0.522	0.008
Rv0006.3	10	1m17_AQ4_A_999 PDB CREDO	0.589	0.192	0.519	0.008
Rv0006_3ilw_A	1	3s23_CER_A_359 PDB CREDO	0.585	0.198	0.517	0.008
Rv0006_3ilw_A	1	3ijx_HCZ_D_800 PDB CREDO	0.579	0.205	0.516	0.009
Rv0006_3ilw_A	2	4e3a_ADN_A_500 PDB CREDO	0.582	0.202	0.516	0.009
Rv0006_3ilw_A	2	1dwc_MIT_H_1 PDB CREDO	0.535	0.266	0.515	0.009
Rv0006_3ilw_A	2	3u9f_CLM_R_221 PDB CREDO	0.514	0.296	0.514	0.009
Rv0006.3	10	2ito_IRE_A_2020 PDB CREDO	0.684	0.093	0.514	0.009
Rv0006.3	10	1r9o_FLP_A_501 PDB CREDO	0.561	0.228	0.513	0.009
Rv0006.3	10	3r9c_ECL_A_451 PDB CREDO	0.717	0.069	0.513	0.009
Rv0006_3ilw_A	2	3nrr_D16_B_530 PDB CREDO	0.553	0.240	0.511	0.009
Rv0006_3ilw_A	2	3u9f_CLM_J_221 PDB CREDO	0.511	0.302	0.511	0.009
Rv0006.3	10	3ug2_IRE_A_1 PDB CREDO	0.644	0.131	0.510	0.009
Rv0006_3ilw_A	2	1a27_EST_A_350 PDB CREDO	0.509	0.304	0.509	0.009
Rv0006_3ilw_A	2	3g0e_B49_A_9000 PDB CREDO	0.550	0.244	0.508	0.010
Rv0006.3	10	3ri5_IVM_E_349 PDB CREDO	0.626	0.149	0.508	0.010
Rv0006.3	10	1ict_T44_C_128 PDB CREDO	0.575	0.210	0.506	0.010
Rv0006.3	5	2y7j_B49_C_1294 PDB CREDO	0.531	0.272	0.505	0.010
Rv0006.3	10	1uay_ADN_A_1001 PDB CREDO	0.551	0.243	0.503	0.010
Rv0006.3	10	3sxr_1N1_A_1 PDB CREDO	0.619	0.157	0.503	0.010
Rv0006_3ilw_A	2	1lhu_EST_A_301 PDB CREDO	0.605	0.173	0.503	0.011

Similarity to known drug target from sensitive sequence analysis

DrugBank ID	Drug Name
DB00218DrugBank	Moxifloxacin
DB00467DrugBank	Enoxacin
DB00487DrugBank	Pefloxacin
DB00537DrugBank	Ciprofloxacin
DB00685DrugBank	Trovafloxacin
DB00817DrugBank	Rosoxacin
DB00978DrugBank	Lomefloxacin
DB01044DrugBank	Gatifloxacin
DB01059DrugBank	Norfloxacin
DB01137DrugBank	Levofloxacin
DB01155DrugBank	Gemifloxacin
DB01165DrugBank	Ofloxacin
DB01208DrugBank	Sparfloxacin
DB04576DrugBank	Fleroxacin
DB06771DrugBank	Besifloxacin

List of small molecules tested from TIBLE

View results in TIBLE page

Name	Affinity	Assay description	DOI
CHEMBL1256993	IC50 = 2.9 uM	Inhibition of DNA supercoiling activity of wild type Mycobacterium tuberculosis DNA gyrase A	http://www.ncbi.nlm.nih.gov/pubmed/20516287
CHEMBL31	IC50 = 9.4 uM	Inhibition of DNA supercoiling activity of wild type Mycobacterium tuberculosis DNA gyrase A	http://www.ncbi.nlm.nih.gov/pubmed/20516287
CHEMBL32	IC50 = 9.2 uM	Inhibition of DNA supercoiling activity of wild type Mycobacterium tuberculosis DNA gyrase A	http://www.ncbi.nlm.nih.gov/pubmed/20516287
CHEMBL33	IC50 = 52 uM	Inhibition of DNA supercoiling activity of wild type Mycobacterium tuberculosis DNA gyrase A	http://www.ncbi.nlm.nih.gov/pubmed/20516287
CDD-1419972	None	None	None
CDD-151	None	None	None
CDD-341142	None	None	None
CDD-341143	None	None	None
CDD-341144	None	None	None
CDD-341145	None	None	None
CDD-341146	None	None	None
CDD-341147	None	None	None
CDD-341148	None	None	None
CDD-341150	None	None	None
CDD-341151	None	None	None
CDD-341152	None	None	None
CDD-341153	None	None	None
CDD-341154	None	None	None
CDD-341155	None	None	None
CDD-341156	None	None	None
CDD-341173	None	None	None
CDD-341174	None	None	None
CDD-341175	None	None	None
CDD-341176	None	None	None
CDD-341177	None	None	None
CDD-46615	None	None	None
CDD-633	None	None	None

Off-target activity - ligand based from TIBLE

View results in TIBLE page

Predicted off-target	Method	Summary	Full results
Cellular retinoic acid-binding protein 2 1CBS	PharmMapper	7 hydroph + 2 HB + 1 pos/neg + 0 arom	Link
Heat shock protein HSP 90-alpha 1UYH	PharmMapper	5 hydroph + 5 HB + 0 pos/neg + 0 arom	Link
GTPase HRas 5P21	PharmMapper	0 hydroph + 13 HB + 2 pos/neg + 0 arom	Link
GTPase HRas 5P21	PharmMapper	0 hydroph + 13 HB + 2 pos/neg + 0 arom	Link
Dipeptidyl peptidase 4 1RWQ	PharmMapper	4 hydroph + 2 HB + 1 pos/neg + 0 arom	Link
Topoisomerase II	PASS	Pa = 0.98 & SM = CHEMBL1256993	Link
DNA topoisomerase IV	PASS	Pa = 0.861 & SM = CHEMBL1256993	Link
DNA topoisomerase II alpha	SEA	E_value = 8.05e-99 & MaxTC = 0.47	Link
Penem	SEA	E_value = 2.35e-50 & MaxTC = 0.57	Link
Taq polymerase 1	SEA	E_value = 4.75e-38 & MaxTC = 0.44	Link
Oxacephem	SEA	E_value = 1.56e-24 & MaxTC = 0.36	Link
Topoisomerase Inhibitor	SEA	E_value = 2.58e-18 & MaxTC = 0.6	Link
Dihydrofolate Reductase Inhibitor	SEA	E_value = 2.8e-16 & MaxTC = 0.45	Link
penicillin-insensitive transglycosylase; penicillin-sensitive transpeptidase [-]	SEA	E_value = 1.91e-14 & MaxTC = 0.51	Link
peptidoglycan synthetase ftsI precursor; peptidoglycan glycosyltransferase 3; penicillin-binding protein 3 [-]	SEA	E_value = 8.49e-11 & MaxTC = 0.51	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
glycerolPubChem	0.978	92.0938
ciprofloxacinPubChem	0.962	331.342
moxifloxacinPubChem	0.956	401.431
ofloxacinPubChem	0.955	361.367
levofloxacinPubChem	0.942	361.367
gatifloxacinPubChem	0.926	375.394
sparfloxacinPubChem	0.925	392.4
sitafloxacinPubChem	0.909	409.814
rifampicinPubChem	0.909	822.94
novobiocinPubChem	0.9	611.616
2-methyl-2,4-pentanediolPubChem	0.9	118.174
(4s)-2-Methyl-2,4-PentanediolPubChem	0.9	118.174
Na(+)PubChem	0.9	22.9898
nalidixic acidPubChem	0.891	232.235
streptomycinPubChem	0.868	581.574
clinafloxacinPubChem	0.864	402.248
garenoxacinPubChem	0.855	426.413
trovafloxacinPubChem	0.835	416.353
tetracyclinePubChem	0.804	444.435
kanamycinPubChem	0.798	484.499
norfloxacinPubChem	0.797	319.331
trioctylphosphine oxidePubChem	0.796	386.635
DU-6859aPubChem	0.795	409.814
erythromycinPubChem	0.789	733.927
oxolinic acidPubChem	0.783	261.23
enrofloxacinPubChem	0.782	359.395
ACH-702PubChem	0.78	432.512
Phe-Arg beta-naphthylamide dihydrochloridePubChem	0.78	446.545
penicillinPubChem	0.779	334.39
pefloxacinPubChem	0.778	333.357
methicillinPubChem	0.773	379.408
gemifloxacinPubChem	0.773	389.381
pazufloxacinPubChem	0.767	318.3
coumermycinPubChem	0.765	1110.08
SmaIPubChem	0.764	147.217
OFLPubChem	0.758	281.23
B-17PubChem	0.757	422.515
chloramphenicolPubChem	0.756	323.129
carbonyl cyanide m-chlorophenylhydrazonePubChem	0.754	204.616
amikacinPubChem	0.751	585.603
ampicillinPubChem	0.749	348.397
grepafloxacinPubChem	0.743	359.395
tosufloxacinPubChem	0.738	404.343
isoniazidPubChem	0.731	137.139
amoxicillinPubChem	0.73	365.404
metronidazolePubChem	0.725	171.154
lomefloxacinPubChem	0.725	351.348
PAEsPubChem	0.724	189.706
tigecyclinePubChem	0.724	585.649
ethambutolPubChem	0.722	204.31
enoxacinPubChem	0.715	320.319
nitratePubChem	0.714	62.0049
clindamycinPubChem	0.713	424.983
ceftriaxonePubChem	0.711	552.564
pyrazinamidePubChem	0.708	123.113
clarithromycinPubChem	0.708	747.953
reserpinePubChem	0.707	608.679
azithromycinPubChem	0.703	748.984