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mbtN | Acyl-CoA dehydrogenase MbtN; Catalyzes the dehydrogenation at the alpha-beta position of ACP-bound acyl chains. This results in the introduction of a double bond in the lipidic chain, which is further transferred to the epsilon- amino group of lysine residue in the mycobactin core by MbtK. Belongs to the acyl-CoA dehydrogenase family. (386 aa) | ||||
cysD | Rv1285, (MTCY373.04), len: 332 aa. Probable cysD,sulfate adenylyltransferase subunit 2 (see Wooff et al.,2002), homology suggests start site at aa 24 or 28, similar to e.g. CYSD_ECOLI|P21156 sulfate adenylate transferase subunit 2 from Escherichia coli (302 aa), FASTA score: opt: 973, E():0, (52.5% identity in 303 aa overlap). Also similar to Mycobacterium tuberculosis Rv2392,3'-phosphoadenylylsulfate reductase. Belongs to the PAPS reductase family. CYSD subfamily. Thought to be differentially expressed within host cells (see Triccas et al., 1999). (332 aa) | ||||
fadB | Rv0860, (MTV043.53), len: 720 aa. Probable fadB,fatty oxidation protein, equivalent to NP_302422.1|NC_002677 putative fatty oxidation complex alpha subunit from Mycobacterium leprae (714 aa). Also highly similar to others and various proteins involved in fatty acid metabolism, e.g. T35429 probable fatty oxidation protein from Streptomyces coelicolor (733 aa); NP_250428.1|NC_002516 probable 3-hydroxyacyl-CoA dehydrogenase from Pseudomonas aeruginosa (714 aa); NP_418895.1|NC_002696 fatty oxidation complex alpha subunit from Caulobacter crescentus (709 aa); P40939|ECHA_HUMAN trifunctional [...] (720 aa) | ||||
fadA | Rv0859, (MTV043.52), len: 403 aa. Possible fadA,acyl-CoA thiolase, equivalent to NP_302423.1|NC_002677 putative beta-ketoadipyl CoA thiolase from Mycobacterium leprae (403 aa). Also highly similar to acyl/acetyl-CoA thiolases and beta-ketoadipyl CoA thiolases, e.g. T35428 probable acetyl CoA acetyltransferase (thiolase) from Streptomyces coelicolor (404 aa); NP_250427.1|NC_002516 probable acyl-CoA thiolase from Pseudomonas aeruginosa (401 aa); NP_106253.1|NC_002678 probable acyl-CoA thiolase from Mesorhizobium loti (402 aa); NP_248919.1|NC_002516|PcaF beta-ketoadipyl CoA thiolase PcaF [...] (403 aa) | ||||
mmpL4 | Probable conserved transmembrane transport protein MmpL4; Part of an export system, which is required for biosynthesis and secretion of siderophores. Essential for normal replication during the active-growth phase of the murine tuberculosis model. (967 aa) | ||||
pks6 | Rv0405, (MTCY22G10.01), len: 1402 aa. Probable pks6,membrane-bound polyketide synthase (see citation below),highly similar to others e.g. CAC29643.1|AL583917 putative polyketide synthase from Mycobacterium leprae (2103 aa); Y06K_MYCTU|Q10977 probable polyketide synthase (1876 aa),FASTA scores: opt: 2303, E(): 0, (38.7% identity in 1232 aa overlap); etc. Contains PS00606 Beta-ketoacyl synthases active site, 2 x PS00017 ATP/GTP-binding site motif A (P-loop), and PS00012 Phosphopantetheine attachment site. (1402 aa) | ||||
eccE3 | ESX-3 secretion system protein EccE3; Part of the ESX-3 specialized secretion system, which is important for iron and zinc uptake or homeostasis. Belongs to the EccE family. (331 aa) | ||||
eccA3 | ESX conserved component EccA3. ESX-3 type VII secretion system protein; Part of the ESX-3 specialized secretion system, which is important for iron and zinc uptake or homeostasis. EccA3 exhibits ATPase activity and may provide energy for the export of ESX-3 substrates (By similarity). Belongs to the CbxX/CfxQ family. (631 aa) | ||||
fadE5 | Rv0244c, (MTV034.10c), len: 611 aa. Probable fadE5,acyl-CoA dehydrogenase, equivalent to AL022486|MLCB1883_15 from Mycobacterium leprae (611 aa), FASTA scores: opt: 3598, E(): 0, (89.4% identity in 611 aa overlap). Also highly similar to AL0211|MTV007.14 from Mycobacterium tuberculosis (609 aa), FASTA scores: opt: 2576, E(): 0,(64.6% identity in 611 aa overlap); and to various other bacterial proteins described as putative acyl-CoA dehydrogenases e.g. AE0010|AE001025_6 from Archaeoglobus fulgidus (387 aa), FASTA scores: opt: 229, E(): 6.8e-08,(29.8% identity in 409 aa overlap); etc. (611 aa) | ||||
fabG4 | Rv0242c, (MTV034.08c), len: 454 aa. Probable fabG4,3-oxoacyl-[acyl-carrier protein] reductase, equivalent to 3063883|CAA18568.1|AL022486|MLCB1883_13|T44878 3-oxoacyl-[acyl-carrier protein] reductase homolog from Mycobacterium leprae (454 aa), FASTA scores: opt: 2486,E(): 0, (84.8% identity in 454 aa overlap). C-terminal part highly similar to many FabG proteins e.g. U39441|VHU3944 1_2 from Vibrio harveyi (244 aa), FASTA scores: opt: 562,E(): 3.4e-28, (40.2% identity in 241 aa overlap); U91631|PAU91631_3 from Pseudomonas aeruginosa (247 aa),FASTA scores: opt: 584, E(): 1.5e-29, (44.4% i [...] (454 aa) | ||||
cysM | O-phosphoserine sulfhydrylase; Catalyzes the formation of a covalent CysO-cysteine adduct via a sulfur transfer, using the thiocarboxylated sulfur carrier protein CysO-COSH as sulfur donor and O-phospho-L-serine (OPS) as sulfur acceptor. Can also use sodium sulfide as sulfur donor in vitro, albeit with less efficiency, but not thiosulfate or thio-nitro- benzoate. O-acetylserine (OAS) is a very poor substrate in comparison with OPS. May be of particular importance for cysteine biosynthesis in the persistent phase of M.tuberculosis; Belongs to the cysteine synthase/cystathionine beta- sy [...] (323 aa) | ||||
mbtK | Lysine N-acetyltransferase MbtK; Acyltransferase required for the direct transfer of medium- to long-chain fatty acyl moieties from a carrier protein (MbtL) on to the epsilon-amino group of lysine residue in the mycobactin core. (210 aa) | ||||
irtA | Iron-regulated transporter IrtA; Part of the ABC transporter complex IrtAB involved in iron import. Transmembrane domains (TMD) form a pore in the membrane and the ATP-binding domain (NBD) is responsible for energy generation. Required for replication in human macrophages and in mouse lungs. (859 aa) | ||||
irtB | Iron-regulated transporter IrtB; Part of the ABC transporter complex IrtAB involved in iron import. Transmembrane domains (TMD) form a pore in the membrane and the ATP-binding domain (NBD) is responsible for energy generation. Required for replication in human macrophages and in mouse lungs. Belongs to the ABC transporter superfamily. Siderophore- Fe(3+) uptake transporter (SIUT) (TC 3.A.1.21) family. (579 aa) | ||||
fadA4 | Rv1323, (MTCY130.08), len: 389 aa. Probable fadA4,acetyl-CoA acetyltransferase, equivalent to THIL_MYCLE|P46707 possible acetyl-CoA C-acetyltransferase from Mycobacterium leprae (393 aa), FASTA scores: opt: 2218, E(): 0, (87.0% identity in 392 aa overlap). Also highly similar to others e.g. CAB70629.1|AL137242 probable acetoacetyl-CoA thiolase from Streptomyces coelicolor (401 aa); T51772 acetyl-CoA C-acetyltransferase [validated] from Alcaligenes latus (392 aa); etc. Some homologies indicate ATA start codon. Contains PS00098 Thiolases acyl-enzyme intermediate signature, PS00737 Thiola [...] (389 aa) | ||||
pks8 | Rv1662, (MTCY275.01-MTCY06H11.27), len: 1602 aa. Probable pks8, polyketide synthase, similar to many polyketide synthases e.g. ERY2_SACER|Q03132 erythronolide synthase, modules 3 and 4 from Saccharopolyspora erythraea (Streptomyces erythraeus) (3567 aa), FASTA scores: opt: 3319, E(): 0, (45.8% identity in 1619 aa overlap). Also similar to other Mycobacterium tuberculosis probable polyketide synthases e.g. pks7 and pks12. Contains PS00606 Beta-ketoacyl synthases active site and PS01162 Quinone oxidoreductase/zeta-crystallin signature. Note that the similarity extends into the downstream [...] (1602 aa) | ||||
fadB3 | Rv1715, (MTV048.02), len: 304 aa. Probable fadB3,3-hydroxybutyryl-CoA dehydrogenase, highly similar to many e.g. NP_107236.1|NC_002678 3-hydroxybutyryl-CoA dehydrogenase from Mesorhizobium loti (309 aa); NP_250319.1|NC_002516 probable 3-hydroxyacyl-CoA dehydrogenase from Pseudomonas aeruginosa (509 aa); P45856|HBD_BACSU probable 3-hydroxybutyryl-CoA dehydrogenase from Bacillus subtilis (287 aa), FASTA scores: opt: 488, E(): 1.5e-24, (38.7% identity in 279 aa overlap); etc. Could belong to the 3-hydroxyacyl-CoA dehydrogenase family. (304 aa) | ||||
narX | Probable nitrate reductase NarX; Does not seem to have nitrate reductase activity. In the N-terminal section; belongs to the nitrate reductase alpha subunit family. In the C-terminal section; belongs to the nitrate reductase gamma subunit family. (652 aa) | ||||
narK2 | Possible nitrate/nitrite transporter NarK2; Permits nitrate and nitrate transport into E.coli. Belongs to the major facilitator superfamily. Nitrate/nitrite porter (TC 2.A.1.8) family. (395 aa) | ||||
bfrA | Probable bacterioferritin BfrA; Iron-storage protein, whose ferroxidase center binds Fe(2+) ions, oxidizes them by dioxygen to Fe(3+), and participates in the subsequent Fe(3+) oxide mineral core formation within the central cavity of the protein complex. (159 aa) | ||||
katG | Catalase-peroxidase-peroxynitritase T KatG; Bifunctional enzyme with both catalase and broad-spectrum peroxidase activity, oxidizing various electron donors including NADP(H). Protects M.tuberculosis against toxic reactive oxygen species (ROS) including hydrogen peroxide as well as organic peroxides and thus contributes to its survival within host macrophages by countering the phagocyte oxidative burst. Also displays efficient peroxynitritase activity, which may help the bacterium to persist in macrophages. Catalyzes the oxidative activation of the antitubercular pro- drug isoniazid (I [...] (740 aa) | ||||
kasB | 3-oxoacyl-[acyl-carrier protein] synthase 2 KasB (beta-ketoacyl-ACP synthase) (KAS I); Catalyzes the condensation reaction of fatty acid synthesis by the addition to an acyl acceptor of two carbons from malonyl-ACP. (438 aa) | ||||
mbtD | Polyketide synthetase MbtD (polyketide synthase); Rv2381c, (MTCY22H8.04), len: 1004 aa. MbtD,polyketide synthase (see citations below), similar in part to several synthases e.g. Q03132|ERY2_SACER|ERYA erythronolide synthase, modules 3 and 4 from Saccharopolyspora erythraea (Streptomyces erythraeus) (3567 aa), FASTA scores: opt: 971, E(): 1e-46, (29.35% identity in 1043 aa overlap); Q9F829|megaii megalomicin 6-deoxyerythronolide B synthase 2 from Micromonospora megalomicea subsp. nigra (3562 aa), FASTA scores: opt: 787,E(): 2.4e-36, (29.35% identity in 1032 aa overlap); Q9L4W4|NYSB poly [...] (1004 aa) | ||||
mbtA | Bifunctional enzyme MbtA: salicyl-AMP ligase (SAL-AMP ligase) + salicyl-S-ArCP synthetase; Involved in the initial steps of the mycobactin biosynthetic pathway. Catalyzes the salicylation of the aryl carrier protein (ArCP) domain of MbtB through a two-step reaction. The first step is the ATP- dependent adenylation of salicylate to generate a salicyl-AMP intermediate. The second step is the transfer of this activated salicylate to MbtB to form a salicyl-ArCP domain thioester. (565 aa) | ||||
mbtJ | Rv2385, (MTCY253.36c), len: 306 aa. Putative mbtJ,acetyl hydrolase (see citations below), showing some similarity with various hydrolases including acetyl hydrolases e.g. Q9ZBM4|MLCB1450.08|ML0314 putative hydrolase/esterase from Mycobacterium leprae (335 aa),FASTA scores: opt: 449, E(): 6.7e-21, (33.85% identity in 313 aa overlap); AAK47950|MT3591 Esterase from M. tuberculosis strain CDC1551 (327 aa), FASTA scores: opt: 469, E(): 3.6e-22, (35% identity in 283 aa overlap); Q9X8J4|SCE9.22 putative esterase from Streptomyces coelicolor (266 aa), FASTA scores: opt: 430,E(): 8.5e-20,(38% i [...] (306 aa) | ||||
ideR | Iron-dependent repressor and activator IdeR; Metal-dependent DNA-binding protein that controls transcription of many genes involved in iron metabolism. Acts as a repressor of siderophore biosynthesis and as a positive modulator of iron storage. Also regulates expression of transporters, proteins involved in siderophore synthesis, iron storage and transcriptional regulators. (230 aa) | ||||
tgs4 | Putative triacylglycerol synthase (diacylglycerol acyltransferase) Tgs4; Required for maintaining the appropriate mycolic acid composition and permeability of the envelope on its exposure to acidic pH. Upon expression in E.coli functions as a triacylglycerol synthase, making triacylglycerol (TG) from diolein and long-chain fatty acyl-CoA. Has very weak wax synthase activity, incorporating palmityl alcohol into wax esters in the presence of palmitoyl-CoA. (474 aa) | ||||
fadD13 | Probable chain-fatty-acid-CoA ligase FadD13 (fatty-acyl-CoA synthetase); Required for maintaining the appropriate mycolic acid composition and permeability of the envelope on its exposure to acidic pH. Catalyzes the activation of long-chain fatty acids as acyl-coenzyme A (acyl-CoA), which are then transferred to the multifunctional polyketide synthase (PKS) type III for further chain extension. It has preference for the fatty acid with long chain length in the following order: hexacosanoic acid (C26), tetracosanoic acid (C24) and palmitic acid (C16); Belongs to the ATP-dependent AMP-bi [...] (503 aa) | ||||
tgs1 | Triacylglycerol synthase (diacylglycerol acyltransferase) Tgs1; Catalyzes the terminal and only committed step in triacylglycerol synthesis by using diacylglycerol and fatty acyl CoA as substrates. Required for storage lipid synthesis (Probable). (463 aa) | ||||
devR | Two component transcriptional regulatory protein DevR (probably LuxR/UhpA-family); Member of the two-component regulatory system DevR/DevS (also called DosR/DosS) involved in onset of the dormancy response. Regulates an approximately 48-member regulon. When phosphorylated binds and activates the promoter of DevR regulon genes in response to hypoxia. The presence of target DNA increases stability of phospho-DevR in vitro. Activates its own transcription under hypoxic but not aerobic conditions, probably binds as a dimer to tandem binding sites within the devR and hspX promoters. Accepts [...] (217 aa) | ||||
ctpC | Probable metal cation-transporting P-type ATPase C CtpC; High affinity, slow turnover Mn(2+) transporting ATPase, which is required for virulence. Controls the Mn(2+) cytoplasmic quota and is involved in the uploading of Mn(2+) into secreted metalloproteins. Required for tolerance to Zn(2+) and oxidative stress. Plays a crucial role in the ability to resist zinc poisoning in human macrophages. Shows a preference for Mn(2+), but Zn(2+), Co(2+) and Cu(2+) can act as alternative substrates although at slower turnover rates ; Belongs to the cation transport ATPase (P-type) (TC 3.A.3) famil [...] (718 aa) | ||||
Rv3371 | Possible triacylglycerol synthase (diacylglycerol acyltransferase); Catalyzes the terminal and only committed step in triacylglycerol synthesis by using diacylglycerol and fatty acyl CoA as substrates. Required for storage lipid synthesis (By similarity). (446 aa) | ||||
whiB3 | Transcriptional regulatory protein WhiB-like WhiB3. Contains [4FE-4S] cluster; A redox-sensitive transcriptional regulator. Maintains intracellular redox homeostasis by regulating catabolic metabolism and polyketide biosynthesis. Regulates expression of the redox buffer ergothioneine (ERG) in a carbon-source- dependent manner; loss of ERG or mycothiol (MSH, the other major redox buffer in this bacteria) leads to respiratory alterations and bioenergetic deficiencies that negatively impact virulence. In response to low external pH (like that found in host macrophage phagosomes) alters en [...] (102 aa) | ||||
fadA6 | Rv3556c, (MTCY06G11.03), len: 386 aa. Probable fadA6, acetyl-CoA acetyltransferase, similar to many e.g. Q9K409|2SCG61.06c from Streptomyces coelicolor (389 aa),FASTA scores: opt: 1091, E(): 2.9e-58, (48.1% identity in 399 aa overlap); Q9AAT4|CC0510 from Caulobacter crescentus (391 aa), FASTA scores: opt: 902, E(): 6.6e-47, (40.25% identity in 395 aa overlap); P45359|THL_CLOAB from Clostridium acetobutylicum (392 aa), FASTA scores: opt: 872, E(): 4.2e-45, (37.9% identity in 396 aa overlap); Q9I2A8|ATOB|PA2001 from Pseudomonas aeruginosa (393 aa),FASTA scores: opt: 872, E(): 4.2e-45, (4 [...] (386 aa) | ||||
pks2 | Polyketide synthase Pks2; Catalyzes the synthesis of the hepta- and octamethyl phthioceranic acids and/or hydroxyphthioceranic acids that are the major acyl constituents of sulfolipids. (2126 aa) | ||||
bfrB | Bacterioferritin BfrB; Iron-storage protein that displays ferroxidase activity, catalyzing the oxidation of Fe(2+) ions into Fe(3+) ions, that can then be deposited as a ferric-oxide mineral core within the central cavity of the protein complex; Belongs to the ferritin family. Prokaryotic subfamily. (181 aa) | ||||
cysN | Sulfate adenylyltransferase subunit 1; ATP sulfurylase may be the GTPase, regulating ATP sulfurylase activity; In the C-terminal section; belongs to the APS kinase family. (614 aa) |