2.02012-07-30 14:55:04 -06002015-06-03 17:20:58 -0600ECMDB21235M2MDB001643KDO(2)-lipid IV(A)Kdo(2)-lipid iv(a) belongs to the class of Polysaccharide Phosphates. These are polysaccharides in which a phosphate group is bound to at least one carbohydrate unit. (inferred from compound structure)(2R,4R,5R,6R)-2-(2R,4R,5R,6R)-2-Carboxy-6-(1R)-1,2-dihydroxyethyl-5-hydroxy-2-(2R,3S,4R,5R,6R)-6-(2R,3S,4R,5R,6R)-3-hydroxy-5-(3R)-3-hydroxytetradecanoylamino-4-(3R)-3-hydroxytetradecanoyloxy-6-phosphonooxyoxan-2-ylmethoxy-5-(3R)-3-hydroxytetradecanoylamino-4-(3R)-3-hydroxytetradecanoyloxy-3-phosphonooxyoxan-2-ylmethoxyoxan-4-yloxy-6-(1R)-1,2-dihydroxyethyl-4,5-dihydroxyoxane-2-carboxylate(2R,4R,5R,6R)-2-(2R,4R,5R,6R)-2-carboxy-6-(1R)-1,2-dihydroxyethyl-5-hydroxy-2-(2R,3S,4R,5R,6R)-6-(2R,3S,4R,5R,6R)-3-hydroxy-5-(3R)-3-hydroxytetradecanoylamino-4-(3R)-3-hydroxytetradecanoyloxy-6-phosphonooxyoxan-2-ylmethoxy-5-(3R)-3-hydroxytetradecanoylamino-4-(3R)-3-hydroxytetradecanoyloxy-3-phosphonooxyoxan-2-ylmethoxyoxan-4-yloxy-6-(1R)-1,2-dihydroxyethyl-4,5-dihydroxyoxane-2-carboxylic acid(2R,4R,5R,6R)-4-(2R,4R,5R,6R)-2-Carboxy-6-(1R)-1,2-dihydroxyethyl-4,5-dihydroxy-tetrahydropyran-2-yloxy-6-(1R)-1,2-dihydroxyethyl-5-hydroxy-2-(2R,3S,4R,5R,6R)-6-(2R,3S,4R,5R,6R)-3-hydroxy-5-(3R)-3-hydroxytetradecanoylamino-4-(3R)-3-hydroxytetradecanoyloxy-6-phosphonooxy-tetrahydropyran-2-ylmethoxy-5-(3R)-3-hydroxytetradecanoylamino-4-(3R)-3-hydroxytetradecanoyloxy-3-phosphonooxy-tetrahydropyran-2-ylmethoxytetrahydropyran-2-carboxylate(2R,4R,5R,6R)-4-(2R,4R,5R,6R)-2-carboxy-6-(1R)-1,2-dihydroxyethyl-4,5-dihydroxy-tetrahydropyran-2-yloxy-6-(1R)-1,2-dihydroxyethyl-5-hydroxy-2-(2R,3S,4R,5R,6R)-6-(2R,3S,4R,5R,6R)-3-hydroxy-5-(3R)-3-hydroxytetradecanoylamino-4-(3R)-3-hydroxytetradecanoyloxy-6-phosphonooxy-tetrahydropyran-2-ylmethoxy-5-(3R)-3-hydroxytetradecanoylamino-4-(3R)-3-hydroxytetradecanoyloxy-3-phosphonooxy-tetrahydropyran-2-ylmethoxytetrahydropyran-2-carboxylic acidDi3-deoxy-D-manno-octulosonyl-lipid IV(A)KDO2-lipid IV(A)C84H154N2O37P21846.06031844.970566976(2R,4R,5R,6R)-4-{[(2R,4R,5R,6R)-2-carboxy-6-[(1R)-1,2-dihydroxyethyl]-4,5-dihydroxyoxan-2-yl]oxy}-6-[(1R)-1,2-dihydroxyethyl]-5-hydroxy-2-{[(2R,3S,4R,5R,6R)-6-{[(2R,3S,4R,5R,6R)-3-hydroxy-5-[(3R)-3-hydroxytetradecanamido]-4-{[(3R)-3-hydroxytetradecanoyl]oxy}-6-(phosphonooxy)oxan-2-yl]methoxy}-5-[(3R)-3-hydroxytetradecanamido]-4-{[(3R)-3-hydroxytetradecanoyl]oxy}-3-(phosphonooxy)oxan-2-yl]methoxy}oxane-2-carboxylic acid(kdo)2-lipid iva143600-83-3[H]OC(=O)[C@]1(OC([H])([H])[C@@]2([H])O[C@@]([H])(OC([H])([H])[C@@]3([H])O[C@]([H])(OP(=O)(O[H])O[H])[C@]([H])(N([H])C(=O)C([H])([H])[C@]([H])(O[H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H])[C@@]([H])(OC(=O)C([H])([H])[C@]([H])(O[H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H])[C@]3([H])O[H])[C@]([H])(N([H])C(=O)C([H])([H])[C@]([H])(O[H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H])[C@@]([H])(OC(=O)C([H])([H])[C@]([H])(O[H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H])[C@]2([H])OP(=O)(O[H])O[H])O[C@]([H])([C@]([H])(O[H])C([H])([H])O[H])[C@]([H])(O[H])[C@]([H])(O[C@]2(O[C@]([H])([C@]([H])(O[H])C([H])([H])O[H])[C@]([H])(O[H])[C@]([H])(O[H])C2([H])[H])C(=O)O[H])C1([H])[H]InChI=1S/C84H154N2O37P2/c1-5-9-13-17-21-25-29-33-37-41-55(89)45-65(96)85-69-77(117-67(98)47-57(91)43-39-35-31-27-23-19-15-11-7-3)73(102)63(115-80(69)123-125(110,111)112)53-113-79-70(86-66(97)46-56(90)42-38-34-30-26-22-18-14-10-6-2)78(118-68(99)48-58(92)44-40-36-32-28-24-20-16-12-8-4)76(122-124(107,108)109)64(116-79)54-114-83(81(103)104)50-62(72(101)75(120-83)61(95)52-88)119-84(82(105)106)49-59(93)71(100)74(121-84)60(94)51-87/h55-64,69-80,87-95,100-102H,5-54H2,1-4H3,(H,85,96)(H,86,97)(H,103,104)(H,105,106)(H2,107,108,109)(H2,110,111,112)/t55-,56-,57-,58-,59-,60-,61-,62-,63-,64-,69-,70-,71-,72-,73-,74-,75-,76-,77-,78-,79-,80-,83-,84-/m1/s1XAOLJGCZESYRFT-VHSKNIDJSA-NCytosolExtra-organismMembranePeriplasmlogp9.83pka_strongest_acidic0.6iupac(2R,4R,5R,6R)-4-{[(2R,4R,5R,6R)-2-carboxy-6-[(1R)-1,2-dihydroxyethyl]-4,5-dihydroxyoxan-2-yl]oxy}-6-[(1R)-1,2-dihydroxyethyl]-5-hydroxy-2-{[(2R,3S,4R,5R,6R)-6-{[(2R,3S,4R,5R,6R)-3-hydroxy-5-[(3R)-3-hydroxytetradecanamido]-4-{[(3R)-3-hydroxytetradecanoyl]oxy}-6-(phosphonooxy)oxan-2-yl]methoxy}-5-[(3R)-3-hydroxytetradecanamido]-4-{[(3R)-3-hydroxytetradecanoyl]oxy}-3-(phosphonooxy)oxan-2-yl]methoxy}oxane-2-carboxylic acidaverage_mass1846.0603mono_mass1844.970566976smiles[H]OC(=O)[C@]1(OC([H])([H])[C@@]2([H])O[C@@]([H])(OC([H])([H])[C@@]3([H])O[C@]([H])(OP(=O)(O[H])O[H])[C@]([H])(N([H])C(=O)C([H])([H])[C@]([H])(O[H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H])[C@@]([H])(OC(=O)C([H])([H])[C@]([H])(O[H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H])[C@]3([H])O[H])[C@]([H])(N([H])C(=O)C([H])([H])[C@]([H])(O[H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H])[C@@]([H])(OC(=O)C([H])([H])[C@]([H])(O[H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H])[C@]2([H])OP(=O)(O[H])O[H])O[C@]([H])([C@]([H])(O[H])C([H])([H])O[H])[C@]([H])(O[H])[C@]([H])(O[C@]2(O[C@]([H])([C@]([H])(O[H])C([H])([H])O[H])[C@]([H])(O[H])[C@]([H])(O[H])C2([H])[H])C(=O)O[H])C1([H])[H]formulaC84H154N2O37P2inchiInChI=1S/C84H154N2O37P2/c1-5-9-13-17-21-25-29-33-37-41-55(89)45-65(96)85-69-77(117-67(98)47-57(91)43-39-35-31-27-23-19-15-11-7-3)73(102)63(115-80(69)123-125(110,111)112)53-113-79-70(86-66(97)46-56(90)42-38-34-30-26-22-18-14-10-6-2)78(118-68(99)48-58(92)44-40-36-32-28-24-20-16-12-8-4)76(122-124(107,108)109)64(116-79)54-114-83(81(103)104)50-62(72(101)75(120-83)61(95)52-88)119-84(82(105)106)49-59(93)71(100)74(121-84)60(94)51-87/h55-64,69-80,87-95,100-102H,5-54H2,1-4H3,(H,85,96)(H,86,97)(H,103,104)(H,105,106)(H2,107,108,109)(H2,110,111,112)/t55-,56-,57-,58-,59-,60-,61-,62-,63-,64-,69-,70-,71-,72-,73-,74-,75-,76-,77-,78-,79-,80-,83-,84-/m1/s1inchikeyXAOLJGCZESYRFT-VHSKNIDJSA-Npolar_surface_area626.29refractivity444.02polarizability195.55rotatable_bond_count72acceptor_count33donor_count20physiological_charge-6formal_charge0Lipopolysaccharide biosynthesisE. coli lipid A is synthesized on the cytoplasmic surface of the inner membrane. The pathway can start from the fructose 6-phosphate that is either produced in the glycolysis and pyruvate dehydrogenase or be obtained from the interaction with D-fructose interacting with a mannose PTS permease. Fructose 6-phosphate interacts with L-glutamine through a D-fructose-6-phosphate aminotransferase resulting into a L-glutamic acid and a glucosamine 6-phosphate. The latter compound is isomerized through a phosphoglucosamine mutase resulting a glucosamine 1-phosphate. This compound is acetylated, interacting with acetyl-CoA through a bifunctional protein glmU resulting in a Coenzyme A, hydrogen ion and N-acetyl-glucosamine 1-phosphate. This compound interact with UTP and hydrogen ion through the bifunctional protein glmU resulting in a pyrophosphate and a UDP-N-acetylglucosamine. This compound interacts with (3R)-3-hydroxymyristoyl-[acp] through an UDP-N-acetylglucosamine acyltransferase resulting in a holo-[acp] and a UDP-3-O[(3R)-3-hydroxymyristoyl]-N-acetyl-alpha-D-glucosamine. This compound interacts with water through UDP-3-O-acyl-N-acetylglucosamine deacetylase resulting in an acetic acid and UDP-3-O-(3-hydroxymyristoyl)-α-D-glucosamine. The latter compound interacts with (3R)-3-hydroxymyristoyl-[acp] through
UDP-3-O-(R-3-hydroxymyristoyl)-glucosamine N-acyltransferase releasing a hydrogen ion, a holo-acp and UDP-2-N,3-O-bis[(3R)-3-hydroxytetradecanoyl]-α-D-glucosamine. The latter compound is hydrolase by interacting with water and a UDP-2,3-diacylglucosamine hydrolase resulting in UMP, hydrogen ion and 2,3-bis[(3R)-3-hydroxymyristoyl]-α-D-glucosaminyl 1-phosphate. This last compound then interacts with a UDP-2-N,3-O-bis[(3R)-3-hydroxytetradecanoyl]-α-D-glucosamine through a lipid A disaccharide synthase resulting in a release of UDP, hydrogen ion and a lipid A disaccharide. The lipid A disaccharide is phosphorylated by an ATP mediated
tetraacyldisaccharide 4'-kinase resulting in the release of hydrogen ion and lipid IVA.
A D-ribulose 5-phosphate is isomerized with D-arabinose 5-phosphate isomerase 2 to result in a D-arabinose 5-phosphate. This compounds interacts with water and phosphoenolpyruvic acid through a 3-deoxy-D-manno-octulosonate 8-phosphate synthase resulting in the release of phosphate and 3-deoxy-D-manno-octulosonate 8-phosphate. This compound interacts with water through a 3-deoxy-D-manno-octulosonate 8-phosphate phosphatase thus releasing a phosphate and a 3-deoxy-D-manno-octulosonate. The latter compound interacts with CTP through a 3-deoxy-D-manno-octulosonate cytidylyltransferase resulting in a pyrophosphate and
CMP-3-deoxy-α-D-manno-octulosonate.
CMP-3-deoxy-α-D-manno-octulosonate and lipid IVA interact with each other through a KDO transferase resulting in CMP, hydrogen ion and alpha-Kdo-(2-->6)-lipid IVA. The latter compound reacts with CMP-3-deoxy-α-D-manno-octulosonate through a KDO transferase resulting in a CMP, hydrogen ion, and a a-Kdo-(2->4)-a-Kdo-(2->6)-lipid IVA. The latter compound interacts with a dodecanoyl-[acp] lauroyl acyltransferase resulting in a holo-[acp] and a (KDO)2-(lauroyl)-lipid IVA. The latter compound reacts with a myristoyl-[acp] through a myristoyl-acyl carrier protein (ACP)-dependent acyltransferase resulting in a holo-[acp], (KDO)2-lipid A. The latter compound reacts with ADP-L-glycero-beta-D-manno-heptose through ADP-heptose:LPS heptosyltransferase I resulting hydrogen ion, ADP, heptosyl-KDO2-lipid A. The latter compound interacts with ADP-L-glycero-beta-D-manno-heptose through ADP-heptose:LPS heptosyltransferase II resulting in ADP, hydrogen ion and (heptosyl)2-Kdo2-lipid A. The latter compound UDP-glucose interacts with (heptosyl)2-Kdo2-lipid A resulting in UDP, hydrogen ion and glucosyl-(heptosyl)2-Kdo2-lipid A. Glucosyl-(heptosyl)2-Kdo2-lipid A (Escherichia coli) is phosphorylated through an ATP-mediated lipopolysaccharide core heptose (I) kinase resulting in ADP, hydrogen ion and glucosyl-(heptosyl)2-Kdo2-lipid A-phosphate.
The latter compound interacts with ADP-L-glycero-beta-D-manno-heptose through a lipopolysaccharide core heptosyl transferase III resulting in ADP, hydrogen ion, and glucosyl-(heptosyl)3-Kdo2-lipid A-phosphate. The latter compound is phosphorylated through an ATP-driven lipopolysaccharide core heptose (II) kinase resulting in ADP, hydrogen ion and glucosyl-(heptosyl)3-Kdo2-lipid A-bisphosphate. The latter compound interacts with UDP-alpha-D-galactose through a UDP-D-galactose:(glucosyl)lipopolysaccharide-1,6-D-galactosyltransferase resulting in a UDP, a hydrogen ion and a galactosyl-glucosyl-(heptosyl)3-Kdo2-lipid A-bisphosphate. The latter compound interacts with UDP-glucose through a (glucosyl)LPS α-1,3-glucosyltransferase resulting in a hydrogen ion, a UDP and galactosyl-(glucosyl)2-(heptosyl)3-Kdo2-lipid A-bisphosphate. This compound then interacts with UDP-glucose through a UDP-glucose:(glucosyl)LPS α-1,2-glucosyltransferase resulting in UDP, a hydrogen ion and galactosyl-(glucosyl)3-(heptosyl)3-Kdo2-lipid A-bisphosphate. This compound then interacts with ADP-L-glycero-beta-D-manno-heptose through a lipopolysaccharide core biosynthesis; heptosyl transferase IV; probably hexose transferase resulting in a Lipid A-core.
A lipid A-core is then exported into the periplasmic space by a lipopolysaccharide ABC transporter.
The lipid A-core is then flipped to the outer surface of the inner membrane by the ATP-binding cassette (ABC) transporter, MsbA. An additional integral membrane protein, YhjD, has recently been implicated in LPS export across the IM. The smallest LPS derivative that supports viability in E. coli is lipid IVA. However, it requires mutations in either MsbA or YhjD, to suppress the normally lethal consequence of an incomplete lipid A . Recent studies with deletion mutants implicate the periplasmic protein LptA, the cytosolic protein LptB, and the IM proteins LptC, LptF, and LptG in the subsequent transport of nascent LPS to the outer membrane (OM), where the LptD/LptE complex flips LPS to the outer surface. PW000831ec00540Metabolicsuperpathway of lipopolysaccharide biosynthesisLPSSYN-PWYSpecdb::EiMs4381Specdb::MsMs3642057Specdb::MsMs3642058Specdb::MsMs3642059Specdb::MsMs3642060Specdb::MsMs3642061Specdb::MsMs364206230833822340609C06025Keseler, I. M., Collado-Vides, J., Santos-Zavaleta, A., Peralta-Gil, M., Gama-Castro, S., Muniz-Rascado, L., Bonavides-Martinez, C., Paley, S., Krummenacker, M., Altman, T., Kaipa, P., Spaulding, A., Pacheco, J., Latendresse, M., Fulcher, C., Sarker, M., Shearer, A. G., Mackie, A., Paulsen, I., Gunsalus, R. P., Karp, P. D. (2011). "EcoCyc: a comprehensive database of Escherichia coli biology." Nucleic Acids Res 39:D583-D590.21097882Kanehisa, M., Goto, S., Sato, Y., Furumichi, M., Tanabe, M. (2012). "KEGG for integration and interpretation of large-scale molecular data sets." Nucleic Acids Res 40:D109-D114.220805103-deoxy-D-manno-octulosonic-acid transferaseP0AC75KDTA_ECOLIwaaAhttp://ecmdb.ca/proteins/P0AC75.xmlLipid A biosynthesis lauroyl acyltransferaseP0ACV0HTRB_ECOLIhtrBhttp://ecmdb.ca/proteins/P0ACV0.xmlUndecaprenyl phosphate-alpha-4-amino-4-deoxy-L-arabinose arabinosyl transferaseP76473ARNT_ECOLIarnThttp://ecmdb.ca/proteins/P76473.xmlLipopolysaccharide export system permease protein lptGP0ADC6LPTG_ECOLIlptGhttp://ecmdb.ca/proteins/P0ADC6.xmlLipopolysaccharide export system permease protein lptFP0AF98LPTF_ECOLIlptFhttp://ecmdb.ca/proteins/P0AF98.xmlLipid A export ATP-binding/permease protein msbAP60752MSBA_ECOLImsbAhttp://ecmdb.ca/proteins/P60752.xmlProtein ddgP0ACV2DDG_ECOLIddghttp://ecmdb.ca/proteins/P0ACV2.xmlLipopolysaccharide export system ATP-binding protein lptBP0A9V1LPTB_ECOLIlptBhttp://ecmdb.ca/proteins/P0A9V1.xmlLipopolysaccharide export system protein lptCP0ADV9LPTC_ECOLIlptChttp://ecmdb.ca/proteins/P0ADV9.xmlLipopolysaccharide export system protein lptAP0ADV1LPTA_ECOLIlptAhttp://ecmdb.ca/proteins/P0ADV1.xmlLipopolysaccharide export system permease protein lptGP0ADC6LPTG_ECOLIlptGhttp://ecmdb.ca/proteins/P0ADC6.xmlLipopolysaccharide export system permease protein lptFP0AF98LPTF_ECOLIlptFhttp://ecmdb.ca/proteins/P0AF98.xmlLipid A export ATP-binding/permease protein msbAP60752MSBA_ECOLImsbAhttp://ecmdb.ca/proteins/P60752.xmlAdenosine triphosphate + Water + KDO(2)-lipid IV(A) > ADP + Hydrogen ion + Phosphate + KDO(2)-lipid IV(A)Adenosine triphosphate + Water + KDO(2)-lipid IV(A) > ADP + Hydrogen ion + Phosphate + KDO(2)-lipid IV(A)Adenosine triphosphate + Water + KDO(2)-lipid IV(A) > ADP + Hydrogen ion + Phosphate + KDO(2)-lipid IV(A)Adenosine triphosphate + Water + KDO(2)-lipid IV(A) > ADP + Hydrogen ion + Phosphate + KDO(2)-lipid IV(A)Dodecanoyl-ACP (n-C12:0ACP) + KDO(2)-lipid IV(A) > acyl carrier protein + KDO(2)-lipid IV(A) with lauratecis-hexadec-9-enoyl-[acyl-carrier protein] (n-C16:1) + KDO(2)-lipid IV(A) > acyl carrier protein + KDO(2)-lipid IV(A) with palmitoleoylCMP-3-Deoxy-D-manno-octulosonate + KDO-lipid IV(A) > Cytidine monophosphate + Hydrogen ion + KDO(2)-lipid IV(A)Hexadecenoyl-[acyl-carrier protein] + KDO(2)-lipid IV(A) <> (9Z)-Hexadec-9-enoyl-KDO2-lipid IV(A) + Acyl-carrier proteinR10906 Lauroyl-KDO2-lipid IV(A) + Acyl-carrier protein + Dodecanoyl-[acyl-carrier protein] + KDO(2)-lipid IV(A) <> Dodecanoyl-[acyl-carrier protein] + Di[3-deoxy-D-manno-octulosonyl]-lipid IV(A) + Lauroyl-KDO2-lipid IV(A) + Acyl-carrier proteinR05146